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Received: 24 January 2018 | Revised: 21 March 2018 | Accepted: 15 April 2018

DOI: 10.1002/ccd.27656

CORE CURRICULUM

1 Anatomic spectrum of left coronary artery anomalies

2 and associated mechanisms of coronary insufficiency

AQ3 3 Paolo Angelini, MD | Carlo Uribe, MD

Department of Cardiology, Texas Heart

5
Institute, Houston, Texas
Abstract
6 This is a novel re-appraisal of an understudied and misunderstood group of important coronary
7 Correspondence anomalies. The general name of the group is “anomalous origin of the left coronary artery,” but
Paolo Angelini, MD, 6624 Fannin, Suite
8 several additional details should be included in this group of anomalies and the explanation of their
2780, Houston, TX 77030. Email
9 pangelini@leachmancardiology.com pathophysiology. The most lethal form in young athletes or military recruits features intramural
10 aortic proximal course. This comprehensive review is based on a large experience at a dedicated
11 center for coronary artery anomalies, using evolving knowledge (over 20 years) while employing
12 prospective and disciplined programs of evaluation and treatment, according to the nature and
13 severity of each anomaly. The most common pathogenic mechanism of coronary dysfunction
14 relates to intramural coronary course, with or without ectopic origin, leading to variable lateral
15 compression and stenosis inside the aortic tunica media; this compression is present at rest and
16 worsens with exertion. We propose that such variable and dynamic stenoses can be best studied
17 by examining their specific anatomy and clinical presentation, stress testing, and, most importantly,
18 in vivo evaluation by intravascular ultrasonography. Such methods should be used to support indi-
19 vidual risk evaluation and selection among treatment options.
20
21 KEYWORDS
22 coronary anomaly (CORA), coronary blood flow/physiology/microvascular function (CORB), struc-
AQ1 23 tural heart disease intervention (SHDI)
24

25

26 1 | INTRODUCTION variable manifestations (Figure 2 and Supporting Information, Figure 43F1

S-1; Table 1). This nomenclature is becoming widely used [2,3] to iden- 44T1
27 For decades, pathologists warned that sudden cardiac death (SCD) tify any coronary artery variant with an abnormal aortic origin. To this 45
28 could be associated with anomalous aortic origin of the left or right term we add an “L” or “R” prefix to indicate the affected coronary 46
29 coronary artery [1]. We submit that the full spectrum of left coronary artery (LCA or RCA) and a suffix to indicate the abnormal proximal 47
30 artery (LCA) anomalies was not well-recognized until now, and we course: “IM” for intramural, “PP” for prepulmonic, “SP” for subpulmo- 48
31 attempt to summarize our referral center’s large accumulated experi- nary, “RA” for retroaortic, “RC” for retrocardiac, or “WA” for wrapping 49
32 ence. We will discuss (1) the prevalence of LCA anomalies in general around the apex [4]. L-ACAOS-IM constitutes the most serious group 50
33 populations (essential information for evaluating risk of SCD and prog- of LCA anomalies [4,5]. 51
34 nosis), (2) the large variability of anatomic forms and severity in the gen- We recently reported the prevalence of the most dangerous coro- 52
35 eral family of ectopic coronary arteries, and (3) the various mechanisms nary anomalies (especially those featuring an IM course), as determined 53
36 of coronary insufficiency (myocardial ischemia) associated with each by screening magnetic resonance imaging (s-MRI), in a continuous 54
37 form of anomalous LCA. series of more than 5,000 schoolchildren from the general population 55
38 Terminology is important when discussing complex pathology. Fac- [5]. Our data suggest that close to 0.45% of the US population has 56
39 ing existing contradictory nosology, we recently proposed that one ACAOS: either R-ACAOS-IM (prevalence, 0.35%) or L-ACAOS-IM 57
40 group of LCA anomalies be called “anomalous origin of a coronary (prevalence, 0.1%). This equates to approximately 1,300,000 people in 58
41 artery from the opposite sinus (ACAOS),” because it is a simple and the United States, 300,000 of whom would have L-ACAOS. Other 59
42 easy-to-remember name for a complex group of anomalies with authors and the Congenital Heart Surgeons’ Society Registry (CHSS) 60

Catheter Cardiovasc Interv. 2018;1–9. wileyonlinelibrary.com/journal/ccd V

C 2018 Wiley Periodicals, Inc. | 1

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2 | ANGELINI AND URIBE

added to the definition of AAOCA, as identified by echocardiography 64

or computed tomographic angiography (CTA). Recently, surgical and 65
virtual angioscopy findings were included as criteria [6]. In reality, intra- 66
mural location and, especially, severity of intramural stenosis can be 67
quantified only by intravascular ultrasonography (IVUS) and not by vir- 68
tual angioscopy (Supporting Information, Figures S-2 and S-3). 69

1.1 | Varieties of L-ACAOS 70

COLOR ONLINE AND BW IN PRINT

1.1.1 | Coronary ostial atresia and stenosis (see also the 71

related section in the supporting information) 72

The classification of intrinsic coronary ostial stenosis or atresia (COSA) 73

FIGURE 1 Schematic cartoon showing the most common sites of
ectopic origin and course of L-ACAOS-IM. 1: Origin of the LCA
from the right sinus, with intramural course; 2: peri-commissure; 3.
origin from the noncoronary sinus; 4: orthotopic origin. Colors for
each course are lighter at intramural segments; asterisks indicate
points of exit [Color figure can be viewed at wileyonlinelibrary.
includes several types of congenital ostial narrowing (at the aortic wall 74
level, Supporting Information, Figure S-3). In these cases, the ostium of 75
the LCA features a congenital atretic “membrane” (there may be only a 76
dimple on the inner aortic sinus) or localized stenosis; usually, the distal 77
left main (LM) trunk is a patent cul-de-sac connected with the distal 78
LCA. Most frequently, left ventricular function is normal. The distal LCA 79
is always supplied by large collaterals, which are usually sufficient to 80
maintain at least normal resting blood flow at birth. Some cases of ostial 81
stenosis feature dysplasia of the left coronary leaflet (the developmen- 82
tal mechanism), which ends up sealing off the coronary ostium [7,8]. 83
1.1.2 | L-ACAOS-OT (orthotopic) or isolated intramural, slit- 84

AQ2 com] [Color figure can be viewed at wileyonlinelibrary.com] like LM trunk (Figure 1) 85F2

This anomaly is an exceptional case in which the LCA ostium is in the 86

61 have included all pathologic variants in a single group called generically normal location, but the artery has an acute angle takeoff, implying 87
62 “anomalous aortic origin of a coronary artery” (AAOCA) without sub- dynamic stenosis and phasic lateral intramural compression (which is 88
63 classes or strict definitions [6]. Eventually, interarterial course was worse in systole) [9]. This is a sister variant of L-ACAOS-IM. 89

T AB LE 1 Classification of varieties of L-ACAOS 1.1.3 | L-ACAOS-IM (intramural) (Figures 3–4, Supporting 90F3 F4
Information, S-4) 91
Frequency
Phasic Fixed High- In these cases, the LCA typically originates from the right sinus of Val- 92
Anomaly <0.05% >0.05% stenosis stenosis Spasm risk salva (RSV) (Figure 5), and the segment travelling to the left side has an 93F5
COSA 1 2 2 1 2 2 intramural course inside the aortic tunica media (Figures 3–5, Support- 94

L-ACAOS-OT 1 2 1 1 2 1
ing Information, Figures S-2, S-4, S-5); this variant is sometimes 95
(improperly, in some cases) called the “between the aorta and pulmo- 96
L-ACAOS-IM 2 1 1 1 2 1
nary artery,” “interarterial,” “slit-like,” or “acute angle” variety 97
L-ACAOS-PP 1 2 2 2 1 2 [1,3,6,10–15]. Because the “intramural” course is the essential feature 98
L-ACAOS-SP 2 1 2 2 1 2 that leads to stenosis, that is the recommended name. The LCA can 99

L-ACAOS-RA 2 1 2 2 1 2 originate directly from the RSV wall or from a proximal mixed right- 100
sided coronary trunk (and have an intramural course, just distal to a 101
L-ACAOS-NC 1 2 1 1 2 1
short proximal epicardial common trunk) [9,11]. When an ectopic LCA 102
L-ACAOS-WA 1 2 2 2 1 2
originates from a site on the RCA more than 2 cm distal from the 103
L-ACAOS-SC 1 2 1 2 n.a. 1 ostium, it preferentially takes a prepulmonic course to reach the left 104
Table shows the frequency of each condition in a general population side of the heart. The juxtacommissural variety of L-ACAOS-IM fea- 105
screened by magnetic resonance imaging, the possibility of stenosis tures an ostium close to or above the anterior commissure, with proxi- 106
(fixed, phasic, or transient spasm-related, as shown by intravascular ultra-
mal IM course next to the commissure (Figure 5). 107
sonography and acetylcholine testing), and prognostic risk (high risk of
sudden cardiac death in the young). L-ACAOS-IM includes cases in which the LCA originates from a 108
Abbreviations: COSA, congenital ostial stenosis or atresia; L-ACAOS, left high origin (HO), more than 5 mm above the sinotubular junction (Fig- 109
anomalous origin of a coronary artery from the opposite sinus; L-OT,
ure 6), or from the noncoronary sinus (NC) [15,16] (where, typically, 110F6
orthotopic; L-IM, intramural; L-PP, prepulmonic; L-SP, subpulmonary; L-
RA, retroaortic; L-NC, noncoronary; L-WA, wrapping around the apex; L- the ostium is located at the juxtacommissural area; Supporting Informa- 111
SC, systolic compression; n.a., not applicable. tion, Figure S-2). Less than 50% of these anomalies have IM course 112

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ANGELINI AND URIBE | 3

FIGURE 2 L-ACAOS-IM, orthotopic. A 65-year-old woman presented with progressive, severe angina and heart failure. Initial angiography
showed severe stenosis at normal ostial location (A, asterisk). Intravascular ultrasonographic images in B show absence of atherosclerotic
plaque. Surgical patch ostioplasty produced great clinical results. C. Diagrammatic rendition (Adapted from [9], with permission.)

113 and stenosis. See Nishiyama et al. [16] for a recent clinical literature 1.1.4 | L-ACAOS-PP (prepulmonic, Supporting Information, 119
114 review of L-ACAOS-NC. Figure S-6) 120
115 In a longitudinal plane (Supporting Information, Figure S-2), the rela- The common feature in these cases is that the LCA (or only the left 121
116 tionship varies between the anterior commissure of the aortic valve and anterior descending [LAD]) originates from the RSV (directly or in a 122
117 L-ACAOS-IM. In about 50% of cases, the intramural LCA involves the common trunk with the RCA) and has a proximal (epicardial) course, 123
118 surgically important level of the anterior aortic commissure [6,15,17,18]. anterior to the pulmonary outflow tract. This is commonly considered a 124

FIGURE 3 L-ACAOS-IM. A 65-year-old woman presented with a few months’ history of progressive dyspnea and typical-effort angina. (A)
A catheter angiogram of a single ostium found at the right sinus (left anterior oblique projection) shows a short, common coronary trunk
(asterisk) subdivided into a normal right coronary artery (RCA; dominant) and the left main (LM) coronary artery (B and C indicate locations
where the intravascular ultrasonography [IVUS] images in panels B and C were obtained), which took a tangential course along the sino-
tubular junction (15 mm long, C). IVUS of the proximal (C, intramural) and distal LM trunk (B) shows luminal CSA proximal stenosis of 70%.
Diagram of the surgical treatment (D) shows the creation of the neo-ostium distal to the anterior aortic commissure. Cx indicates circumflex;
LAD, left anterior descending; NURD, non-uniform rotational distortion at atherosclerotic plaque (Adapted from [15], with permission.)

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4 | ANGELINI AND URIBE

FIGURE 4 L-ACAOS-IM (NC). A 62-year-old man presented with progressive angina and dyspnea of several months’ duration. Right ante-
rior (1) and left anterior oblique (2) angiograms showed origin of the left coronary artery (LCA) from the noncoronary sinus of Valsalva next
to the left posterior commissure. Only intravascular ultrasonography of the LCA revealed severe proximal stenosis at the intramural proximal
course (15 mm long [3]), with an area of 1.54 mm2, whereas the distal left main extramural area was 12.6 mm2 (4), for a cross-sectional
area stenosis of 88%. This patient had neo-window surgical creation at the distal left main segment, resulting in excellent functional
improvement. AW indicates aortic wall; C, ostium; D, distal left main; LM, left main (Adapted from [15], with permission.)

125 benign anomaly (without intrinsic stenosis) and does not indicate inter- into the central fibrous body of the heart at the fibrous mitro-aortic 145
126 vention [17–19]. septum. This defect is generally benign. 146

127 1.1.5 | L-ACAOS-SP (subpulmonary, infundibular, or

1.1.7 | L-ACAOS-RC (retrocardiac) or L-ACAOS-WA, wrap 147
128 intramyocardial, Supporting Information, Figures S-7–S-9)
around the apex (Supporting Information, Figures S-10 and 148
129 This term indicates cases in which the LCA (or only the LAD, in about S-11) 149
130 30% of cases) anomalously originates from the RSV, initially runs inter-
These terms describe cases in which the LCA originates from the distal 150
131 arterially, then courses into the supraventricular crest and through the
RCA at the atrioventricular groove (L-ACAOS-RC) or from the distal 151
132 upper- or mid-ventricular septum (intramyocardially), and finally returns
posterior descending coronary artery (wrapping around the apex, L- 152
133 to an epicardial location at the anterior interventricular groove. The
ACAOS-WA, Supporting Information, Figure S-9) [17]. These anomalies 153
134 ostium can be common with the RCA (implying a short proximal com-
are generally benign. 154
135 mon stem) or separate (adjacent). Generally, this anomaly is considered
136 benign and causes no significant stenosis [6,11,17,18]. This type, which
137 was found in 0.04% of our s-MRI screening study participants, is fre- 1.1.8 | L-ACAOS-SC (systolic compression) 155

138 quently confused in clinical practice with L-ACAOS-IM, especially In these cases, most of the LCA has an intramyocardial course and crit- 156
139 because of the simplification implied by the unqualified term originating ically severe SC (i.e., the myocardial bridge effect). This exceptional var- 157
140 from the notion of interarterial course. iant has not yet been completely evaluated. It can occur in at least two 158
forms. In one, the LCA originates from the RSV and courses straight 159
141 1.1.6 | L-ACAOS-RA (retroaortic) (Supporting Information, down the mid-ventricular septum, supplying most of the septal 160
142 Figure S-10) branches and reaching the apex, the lateral free wall of the left ventri- 161
143 In these cases, the LCA originates from the RSV or the RCA itself at cle. In the other form, the LCA has a normal origin, but the LM, LAD, 162
144 the RSV, and the LCA (or a lone Cx) courses behind the aortic root and and Cx have an intramyocardial course (Supporting Information, Figure 163

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ANGELINI AND URIBE | 5

FIGURE 5 L-ACAOS-IM, juxtacommissural. A 24-year-old woman who was an experienced marathon runner had an episode of sudden car-
diac arrest while finishing a 27-mile run. She was resuscitated successfully. Emergency cardiac magnetic resonance imaging (A) showed
anomalous origin of the left coronary artery (LCA) from the juxtacommissural area with intramural course in front of the anterior commis-
sure (asterisks indicate commissures). Selective coronary angiography (right anterior oblique projection, B) shows stenosis of the coronary
ostium (arrow). Initial surgical reimplantation of the LCA into the left sinus of Valsalva (without ostioplasty) resulted in a complicated periop-
erative course because of residual ostial critical stenosis (C, hashtag). After grafting of the left anterior descending (LAD) coronary artery
was attempted (and soon failed because the graft and distal vessel were too small), the patient underwent successful percutaneous stenting
of the left main ostium and of the distal LAD at anastomotic narrowing (stent locations are indicated by asterisks, D). Excellent functional
recovery followed, which was confirmed at 4-year follow-up (negative nuclear stress test results for active ischemia). The patient returned
to running marathons and had an uncomplicated pregnancy

164 S-12) [20]. (See the section titled “Critical Systolic Compression” in the and hypertension predispose patients to clinical manifestations. Clinical 182
165 Supporting Information.) expression during exertion is most common at 18–25 years of age, but 183
symptoms can occur even at rest after age 40–50 years (possibly 184
because of aortic root dilatation and worsening stenosis). 185
166 1.2 | Methods of clinically evaluating L-ACAOS
167 1.2.1 | Clinical history 1.2.2 | Anatomic description 186

168 Adult patients with L-ACAOS-IM sometimes (more frequently than As is currently proposed, the initial diagnostic process may involve pri- 187
169 patients with R-ACAOS) have significant related symptoms, which vary mary s-MRI, if indicated for participation in elite sports or military exer- 188
170 with the severity of intramural stenosis. Patients’ clinical history must cises, or for suspicious symptoms. Confirmatory CTA is then performed 189
171 be carefully evaluated: It is frequently the only way to justify the dis- if clinically indicated in doubtful cases (Supporting Information, Figures 190
172 comfort, cost, and risks associated with catheterization and IVUS, and S-7, S-9, S-13). Currently, we believe that in CTA-proven carriers or 191
173 to determine whether intervention is needed. elite athletes, IVUS should be used to quantify the severity of L- 192
174 L-ACAOS-IM can cause chest pain, dyspnea, dizziness, syncope, ACAOS-IM before surgery or disqualification can be considered. In 193
175 and sudden cardiac arrest/death at any age, typically with exertion. most cases, MRI is a consistent, acceptable, and accurate method of 194
176 However, most people born with such anomalies never manifest symp- diagnosing most subtypes of L-ACAOS (especially the important IM 195
177 toms and die at an older age (more than 25 years) of unrelated causes. course) and does not require intravenous access, contrast, or ionizing 196
178 De facto, such anomalies are identified because of symptoms (5% of radiation [17]. Although L-ACAOS can sometimes be diagnosed by 197
179 children and 30% of adults), stress testing (10% of adults), or imaging expert echocardiography in young patients [3], these conditions (espe- 198
180 (MRI or CTA in adults, echocardiography in children) to rule out coro- cially the serious IM variety) cannot usually be quantitatively diagnosed 199
181 nary artery disease (currently, about 50% of all cases). Active lifestyle by echocardiographic screening. Whereas CTA is more accurate than 200

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6 | ANGELINI AND URIBE

FIGURE 6 R- and L-ACAOS-HO. High origin of both right (RCA) and left coronary artery (LCA) with intramural course and stenosis. Angio-
graphic images show the two arteries in the left anterior oblique (A, R-ACAOS) and the postero-anterior projection (D, L-ACAOS), located
about 5–7 mm above the left sinotubular junction (asterisk). Intravascular ultrasonograms of the two ostia show severe stenosis in both (B,
E) with respect to the distal vessels (C, F). Cross-sectional area stenoses were 66.5% for the RCA and 84% for the LCA. Successful bilateral
patch angioplasty followed. AW indicates aortic wall; LSV, left sinus of Valsalva (Adapted from [15], with permission.)

201 MRI, it is contraindicated for screening because of the risks associated >45% at rest may be clinically significant and may constitute a sound 222
202 with ionizing radiation exposure. Furthermore, CTA allows only gross criterion for intervention. 223
203 and preliminary quantification of a defect’s severity by determining the Virtual angioscopy is a gadolinium-enhanced magnetic resonance 224
204 proximal trunk cross-sectional area (CSA) at the level of the aorto- or CTA post-acquisition method of visualizing ostial morphology in a 3- 225
205 pulmonary septum (the Angelini/Cheong sign; Supporting Information, D format, that was recently tested to evaluate ostial stenosis [6]. Cur- 226
206 Figure S-14). Specifically, a short-to-long diameter ratio >1:2 indicates rently, we believe that virtual angioscopy is adequate to suggest acute 227
207 potentially significant stenosis [10–12]. Measurements are routinely angle origin but that it cannot reliably determine the severity of L- 228
208 obtained with CTA at end-diastole, when the heart is more stable, but ACAOS-IM. In particular, we believe that stenosis cannot be described 229
209 systolic values are more useful in screening athletes, because more by using ostial, frontal imaging but instead requires in vivo measure- 230
210 than 50% of coronary flow is systolic during maximal effort tachycardia ment of the intramural orthogonal cross-section along the IM segment 231
211 [11]. More reliable measurements of intramural segments can be and comparison with a distal reference area. Additionally, in L-ACAOS- 232
212 obtained by using IVUS (Supporting Information, Figures S-14 [and IM, stenosis may not be ostial (Figures 3–5, Supporting Information, 233
213 accompanying video] and S-15) [12]. IVUS is commonly used in adult Figure S-7). 234
214 catheterization laboratories, allowing live imaging (at a rate of 30
215 images/min) during the resting cardiac cycle (Supporting Information, 1.2.3 | Physiologic testing 235

216 Figures S-15 and S-16) or under other testing conditions, and it is cur- Current stress-testing methods (i.e., treadmill, nuclear scintigraphy, 236
217 rently the preferred method of classifying the severity of ACAOS in stress or dobutamine echocardiography, and fractional flow reserve) do 237
218 clinical cases. In all our cases diagnosed by expert angiographers as L- not significantly correlate with clinical symptoms and prognosis [11,12]. 238
219 ACAOS-IM, IVUS has confirmed an intramural course with variable Dobutamine testing in the catheterization laboratory may induce signif- 239
220 degrees of stenosis (resting CSA stenosis, 8%–80%). We currently icant arrhythmias in patients with severe L-ACAOS-IM, much as it does 240
221 believe that in physically active, symptomatic individuals, CSA stenosis in patients with atherosclerotic LM lesions. Adenosine-type testing is 241

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ANGELINI AND URIBE | 7

242 not predictive, because stenosis does not increase with vasodilation as overload increase myocardial demand and decrease coronary flow. This 291
243 it does with physiologic exercise. likely mechanism has not been objectively demonstrated in these rare 292
244 Follow-up studies of the postoperative results of surgical interven- cases, but it could be done in the catheterization laboratory with 293
245 tions for this type of ACAOS should be extensive and precise, espe- dobutamine stress test simulation and blood-flow monitoring. 294
246 cially when bypass surgery is involved [21,22]. Few of the initial
247 attempts to treat L-ACAOS-IM with stenting [23] (much as in R-
1.3.3 | Transient obstruction: Spasm in L-ACAOS 295

248 ACAOS-IM [12]) were reported as successful, even in critically ill new- For some patients with L-ACAOS who have resting angina and no 296
249 borns for whom there were no other practical treatment options [24]. obvious important baseline stenosis, one commonly invoked hypothesis 297
250 Still, the implications of inserting stents into the LM in young patients is that coronary spasm causes intermittent narrowing of the artery. In 298
251 are problematic. clinical practice, spasm is not observed in L-ACAOS-IM unless cannula- 299
tion during a procedure inadvertently results in trauma. Interestingly, in 300

252 1.3 | Mechanisms of coronary insufficiency in patients ACAOS-IM, the artery is embedded in the aortic tunica media, which 301

253 with L-ACAOS cannot cause coronary spasm because it has elastic tissue but no func- 302
tional smooth muscle cells. Recently, we used acetylcholine to test for 303
254 Myocardial ischemia is generally the only manifestation of coronary
endothelial dysfunction in L-ACAOS patients with suggestive symp- 304
255 insufficiency. Here, we discuss three different possible mechanisms of
toms, especially in PP, RA, IS, and WA cases (see Supporting Informa- 305
256 dysfunction in these rare anomalies, acknowledging that our under-
tion, Figures S-6, S-8, S-10), which normally do not have an identifiable 306
257 standing is based on limited experience and still-inconclusive support-
mechanism of intrinsic ischemia at baseline. When spasm occurs in 307
258 ing literature.
such cases, it is usually in middle-aged carriers, is diffuse, is reproduced 308

259 1.3.1 | Stenosis at intramural proximal course by intracoronary acetylcholine infusion, and resolves quickly after nitro- 309

260 (L-ACAOS-IM) glycerine administration. The frequency of this complication is not yet 310
clear, because our experience is only preliminary. Angina at rest, persis- 311
261 Proximal, dynamic coronary stenosis is common and may lead to
tent left ventricular dilated cardiomyopathy (the mechanism of which is 312
262 angina, shortness of breath, and syncopal equivalents or SCD. In fact,
unclear but may involve recurrent, sustained ischemic events), and 313
263 L-ACAOS-IM is the coronary anomaly most commonly associated with
arrhythmias (atrial and ventricular) have been reported, especially in SP 314
264 SCD in young athletes and military recruits [25–27]. In reporting on the
cases. 315
265 incidence of SCD in military recruits, Eckart et al. [25] stated that L-
266 ACAOS-IM was the only coronary anomaly found to cause SCD,
267 accounting for 33% of their SCD cases (21 of 63). In 90% of these 2 | DISCUSSION 316

268 cases, SCD occurred unexpectedly during exertion [26,27]. At times,

Currently, we stress that the term used for each type of LCA anomaly 317
269 the worse stenotic segment is more distal than ostial (unlike in R-
(L-ACAOS) should relate to the nature, mechanism, and severity of the 318
270 ACAOS, when maximal stenosis is always at the ostium). Only IVUS
coronary dysfunction associated with it. That said, some types of L- 319
271 (Supporting Information, Figure S-14) can clearly quantify systolic and
ACAOS (or AAOCA) may not be intrinsically associated with any 320
272 diastolic stenosis with respect to the distal reference CSA [4,12,15].
known mechanism of dysfunction (e.g., retrocardiac). Others are associ- 321
273 Functional stenosis is worse during exertion and/or tachycardia than at
ated with an intrinsic baseline fixed stenosis (e.g., COSA and IM), 322
274 baseline. Stenosis and intramural course are not consistent features of
increased spasticity (e.g., PP, IS, RA), or systolic phasic obstruction (as 323
275 L-ACAOS-NC or -HO (being found only in about 50% of cases, Sup-
shown by IM, SC). 324
276 porting Information, Figures S-4 and S-7) [15,16,23]. Intramural steno-
Our present knowledge regarding L-ACAOS is summarized here: 325
277 sis severity must be measured to determine whether and which
278 interventional treatment is needed, whereas ectopy or interarterial
 Estimating a given L-ACAOS-IM case’s stenosis/prognostic risk 326
279 course alone does not necessarily indicate treatment [11,23]. The
requires quantitative examination by IVUS, or histological examina- 327
280 American Heart Association and American College of Cardiology’s
tion at autopsy. 328
281 most recent guidelines still recommend surgical treatment in any case
 CTA, MRI, or catheter angiography can be used to diagnose qualita- 329
282 of ACAOS with interarterial or between the aorta and pulmonary artery
tively the type of ACAOS [18], but associated stenosis (which is 330
283 course, “especially when symptomatic” [11].
intrinsically dynamic in IM cases) cannot be assessed accurately by 331
284 1.3.2 | Stenosis at left main (or equivalent) by severe this means. Including end-systolic frames is potentially ideal but 332
285 myocardial compression technically difficult (imaging precision). Determining the severity of 333

286 Systolic compression (SC), which is different from IM but similar to resting CSA stenosis is essential (because stenosis >45% in patients 334

287 myocardial bridging, has an additional potential mechanism that con- with significant symptoms, or any stenosis >60%, is associated with 335

288 sists of phasic systolic obliteration of a proximal LM trunk or all of its an elevated risk of SCD in young athletes). 336

289 branches, as mentioned above. Such systolic collapse may induce sig-  In small children, echocardiography performed by expert operators 337
290 nificant LV (global) ischemia when tachycardia and hemodynamic can identify the presence (but not the severity) of some anomalies 338

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8 | ANGELINI AND URIBE

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380 Neither of the authors has any relevant potential conflict of interest
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381 regarding the subject matter discussed here. Heart Inst J 2006;33:171–179. 439

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A, Mizutani S. Exercise-induced myocardial ischemia in a case of 441
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