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A case report of a symptomatic right anomalous coronary artery with concomitant atherosclerotic disease: the benefit of a sequential comprehensive non-invasive and invasive diagnostic approach

Abstract Background  Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital disease associated with an increased risk of myocardial ischaemia, ventricular arrhythmias, and heart failure. Case summary  A 75-year-old Caucasian man was referred for invasive coronary angiography (ICA) due to atypical chest pain. Invasive coronary angiography demonstrated non-significant atherosclerotic disease of the left coronary artery and an anomalous origin of the right coronary artery (RCA); without selective intubation. Coronary computed tomography angiography (CCTA) revealed a right-AAOCA with interarterial and intramural course, and a soft plaque in the distal RCA. Subsequent physical-stress single-photon emissions computed tomography (SPECT) showed exercise-induced inferoapical myocardial ischaemia, giving a Class IC level of evidence for surgical correction of the AAOCA. Repeated ICA with selective R-AAOCA intubation confirmed an 80% distal atherosclerotic stenosis, which was treated with direct stenting. Subsequent invasive physiologic evaluation under maximal dobutamine-volume challenge (gradually increasing dose of dobutamine max. 40 μg/kg per body weight/min, 3000 mL ringer lactate and 1 mg atropine was given until the patient reached a maximum of 145 b.p.m.), revealed a haemodynamically non-relevant anomalous segment with a fractional flow reserve (FFR) of 0.91. A follow-up SPECT was normal, and the patient was completely symptom-free at 1 month. Discussion  We present the sequential diagnostic approach in a symptomatic patient with a right anomalous coronary artery and concomitant atherosclerotic disease. Using this approach, the patient could be deferred from guideline recommended open-heart surgery of the AAOCA, as direct invasive dobutamine/volume FFR revealed haemodynamic non-relevance of the anomalous segment after stenting the concomitant atherosclerotic stenosis in the distal segment within the same coronary artery.


Introduction
Anomalous coronary arteries (CAA) represent a congenital disorder hallmarked by an anomalous location of the coronary ostium and/or vessel course. 1 Of particular interests are CAA with an anomalous aortic origin (AAOCA) and an interarterial course (IC) between the great arteries (i.e. aorta and pulmonary artery), a so-called 'malignant' variant which has been associated with an increased risk of myocardial ischaemia, ventricular arrhythmias, and heart failure. 1 However, the interarterial course itself may not be the predominant cause of ischaemia, but rather represents a surrogate for other anatomical high-risk features associated with ischaemia such as slitlike ostium, acute take-off angle, intramural course (i.e. location of the proximal segment within the tunica media of the aortic wall), oval vessel shape, and proximal narrowing. 1,2 These anatomical features are considered high risk as it is hypothesized that during exercise the aortic dilation may lead to lateral compression and subsequent haemodynamically relevant stenosis of the anomalous segment. 1,2 With increased use of non-invasive imaging in evaluation of coronary artery disease (CAD) in younger, middle-aged, and older individuals, an increase in absolute numbers of AAOCA-IC is expected. Usually, the question is whether the AAOCA-IC is a coincidental finding or if the anomaly is causative for the patients' symptoms. Guidelines are limited and recommendations are mainly based on expert's opinions, which include strict sports abstinence in patients with interarterial courses and a low threshold for surgical coronary revascularization. [3][4][5] Further, in older patients with AAOCA, a higher prevalence of concomitant CAD is noted and ischaemia is more often caused by CAD than the anomaly. 6 However, the optimal management in patients with combined coronary artery anomaly and CAD remains unknown.

Timeline Learning points
• Multimodality cardiac imaging is required for comprehensive assessment of haemodynamic relevance of anomalous aortic origin of a coronary artery (AAOCA), especially in the clinical setting of concomitant atherosclerotic diseases.
• In older patients, myocardial ischaemia is more likely attributable to concomitant atherosclerotic disease than to AAOCA. • The pathophysiology in AAOCA includes a fixed and a dynamic component, which requires a specialized diagnostic workup with supramaximal stress testing.

Case presentation
A 75-year-old Caucasian man was referred for invasive coronary angiography (ICA) due to atypical chest pain. Initial diagnostic workup revealed normal electrocardiographic and laboratory findings. Arterial hypertension, dyslipidaemia, and a history of smoking; cumulative five pack years, were the patient's cardiovascular risk factors. Medications were aspirin, rosuvastatin, and losartan. On physical examination, temperature was normal, blood pressure was 134/85 mmHg, and heartrate was 58 b.p.m. Cardiac examination was normal without pathological sounds or murmurs. Bicycle exercise testing (120 W, 158 b.p.m. ‫-‬ 109% of predicted maximal heartrate) revealed an exercise-induced supraventricular arrhythmia.
Invasive coronary angiography demonstrated non-significant atherosclerotic disease of the left coronary artery and an anomalous origin of the right coronary artery (RCA), although selective intubation was not possible. Subsequently performed coronary computed tomography angiography (CCTA) revealed a right anomalous aortic origin of the coronary artery (R-AAOCA) with an intramural and interarterial course. Further, a soft plaque was seen in the distal RCA ( Figure 1). As recommended, 3,5 a physical stress single-photon emissions computed tomography (SPECT) was performed, demonstrating exercise-induced inferoapical ischaemia (130 b.p.m. ‫-‬ 90% of predicted maximal heartrate), within the territory of R-AAOCA, in the presence of RCA dominance ( Figure 2). Thus, according to the 2020 ESC Guidelines, a Class IC level of evidence is given for surgical correction (i.e. open-heart surgery) of the anomalous vessel. 3 However, in agreement with the patient, a repeat invasive angiography was performed with selective intubation of the R-AAOCA, which confirmed a significant, 80% distal atherosclerotic stenosis ( Figure 2). This lesion was treated with direct stenting (drug-eluting stent: 3.0 mm Â 18 mm). Subsequent invasive physiologic evaluation under a dobutamine/volume-challenge (maximum dobutamine dose of 40 lg/kg per body weight/min, 3000 mL ringer lactate, and 1 mg atropine), 6,7 revealed a haemodynamically non-relevant anomalous segment with a fractional flow reserve of 0.91 (145 b.p.m. ‫-‬ 100% of predicted maximal heartrate). Intravascular ultrasound (IVUS) confirmed the presence of a non-significant anomaly with only mild lateral dynamic compression of the vessel (reduction of the minimal lumen area of 11.5 to 8.1 mm 2 , i.e. 29.6% under maximal dobutamine/volume stress). Consequently, surgical revascularization was refrained. A repeated SPECT after the procedure showed absence of apical myocardial ischaemia (Figure 2), and the patient was completely symptom-free at 1-month follow-up.

Discussion
We present the case of a symptomatic R-AAOCA with concomitant atherosclerotic disease within the same vessel, where a maximal physical exercise non-invasive imaging testing revealed ischaemia in the supplied myocardial territory. While surgical unroofing is the guideline recommended therapy for symptomatic R-AAOCA, percutaneous coronary treatment with drug-eluting stents is preferred treatment in single RCA stenosis. As it was unclear, whether the AAOCA or the atherosclerotic stenosis was responsible for the patient's symptoms and ischaemia, a sequential treatment and diagnostic approach was chosen. Direct stenting of CAD and succeeding invasive diagnostic approach with haemodynamic evaluation of the anomalous course under pharmacologic inotropic stress revealed that the AAOCA was an innocent bystander. The patient was symptom free and could be prevented from unnecessary open-heart surgery using this approach.

Management of patients with anomalous aortic origin of a coronary artery and coronary artery disease
AAOCA is a coronary anomaly with a prevalence of 0.26% in the general population. 8,9 Hence, the level of evidence is limited and current guidelines are often vague with regard to management recommendation. Mostly, surgical revascularization is recommended with a low threshold based on the increased frequency of sports-related sudden cardiac deaths in younger individuals, observed in autopsy series. 10,11 However, the significance of newly diagnosed AAOCA in older patients remains unclear, especially since the haemodynamic relevance of AAOCA may decrease with age while concomitant CAD become increasingly significant. 12 However, also in advanced age, first time appearance of AAOCArelated myocardial ischaemia is possible, as recently described by our group. 6 For the optimal diagnostic and therapeutic management of the AAOCA, one has to consider the underlying pathophysiology. Our group supported a two-tier concept for the pathomechanisms of ischaemia in AAOCA. In detail, this concept states 'the occurrence of ischaemia is based on the extent of a fixed (i.e. anatomic high-risk features as slit-like ostium and proximal narrowing) and a dynamic (i.e. acute take-off angle, intramural course with lateral compression) component'. 13 The latter, which occurs during strenuous physical exercise promoted by aortic dilation and reduced diastolic perfusion time. Further, the mass of viable myocardium supplied by the anomalous coronary artery as well as the distensibility of the aortic wall directly affects the haemodynamic relevance. Taken into account the various components, it is obvious that a thorough diagnostic evaluation requires a multimodality approach.
CCTA is the preferred technique for the qualitative and quantitative assessment of the anatomical high-risk features with