EXPLANATION

Coronary artery disease evaluation in adult congenital heart disease (ACHD) is complicated by the combination of abnormal coronary anatomy, whether congenitally anomalous or altered by prior surgery (such as coronary reimplantation during an arterial switch operation or coronary manipulation during a Ross procedure) together with accelerated atherosclerosis driven by chronic inflammation or aortopathy among others.¹

Baseline electrocardiographic abnormalities from prior surgery, chronic conduction disease, or ventricular hypertrophy frequently obscure or mimic the ST-segment and T-wave changes conventionally used to detect ischemia.¹ Standard exercise stress testing may be unreliable given the limited functional capacity and complex anatomy common in this population, and traditional cardiovascular risk-stratification tools may not necessarily apply to patients with ACHD and thus may not adequately capture their risk. As such, the 2018 AHA Guidelines for the Management of Adults with Congenital Heart Disease recommends obtaining baseline electrocardiograms postoperatively for future comparison, and serial studies, depending on the type of repaired lesion, and if symptoms worsen from baseline.² Commonly observed electrocardiographic findings in patients with repaired TOF include near-universal RBBB, right axis deviation, and diffuse ST/T repolarization abnormalities.⁵ These baseline conduction abnormalities can hamper the detection of ECG-based ischemia, at rest or during exercise testing. Therefore answer A is the correct response.

Answer B (Abnormal native coronary anatomy) is incorrect. Coronary artery anomalies are more common across ACHD as a whole than in the general population, but in isolated Tetralogy of Fallot specifically, an anomalous coronary origin is present in only about 5-6% of patients. Thus, abnormal coronaries are a far less consistent a finding than the conduction abnormalities produced by the ventriculotomy or infundibular resection used during TOF repair, and are even less likely in a patient with a transannular patch repair.³ When present, abnormal coronary anatomy is best understood primarily as a substrate for ischemia rather than a cause of missed detection, though it can also complicate interpretation of stress imaging by disrupting the coronary territories on which conventional interpretation relies.^1,4

Answer C is incorrect because reduced, rather than preserved, exercise tolerance is typical in this population, driven by residual pulmonary regurgitation, right ventricular volume overload, and deconditioning. Notably, patients with repaired TOF frequently self-report normal exercise tolerance despite objectively reduced capacity on cardiopulmonary exercise testing, reflecting a well-documented discordance between subjective symptoms and measured functional capacity in this population.⁶ A patient's own sense of preserved tolerance should therefore not be taken as reassurance, and this discordance further limits the diagnostic yield of standard exercise stress testing.

Traditional atherosclerotic risk factors (hypertension, dyslipidemia, obesity, and physical inactivity) occur at rates broadly similar to those of the general population, with the notable exceptions of a higher prevalence of diabetes mellitus and a lower prevalence of smoking.² This suggests that, for most ACHD patients, conventional cardiovascular risk-factor modification retains an important role even as the underlying anatomic and physiologic substrate for coronary disease differs meaningfully from that of acquired heart disease in the general population.

In patients with more complex CHD, additional lesion-specific mechanisms compound this traditional risk-factor burden. Coronary artery disease may be intrinsically linked to the underlying cardiac anomaly, as in transposition of the great arteries after an arterial switch operation, where reimplanted coronary arteries are prone to kinking, stenosis, and impaired vasodilator reserve, or in Tetralogy of Fallot, where reported CAD prevalence in adult survivors ranges from 15-21%.^1,4 Chronic low-grade inflammation, altered shear stress across anomalous or surgically manipulated vessels, and aortopathy-related arterial stiffness are thought to accelerate atherosclerosis independent of traditional risk factors.¹ Together with the ECG and functional-testing limitations discussed above, these anatomic and physiologic considerations underscore why a high index of suspicion (and, when possible, advanced imaging such as coronary CT angiography) is often needed to identify obstructive CAD in this population before it presents as an acute event.

REFERENCES

1. Borrelli N, Merola A, Barracano R, et al. The Unique Challenge of Coronary Artery Disease in Adult Patients with Congenital Heart Disease. J Clin Med. 2024;13(22):6839. doi:10.3390/jcm13226839

2. Stout KK, Daniels CJ, Aboulhosn JA, et al. 2018 AHA/ACC guideline for the management of adults with congenital heart disease: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73:e81–e192. doi:10.1016/j.jacc.2018.08.1029

3. Kakucs Z, Heidenhoffer E, Pop M. Detection of Coronary Artery and Aortic Arch Anomalies in Patients with Tetralogy of Fallot Using CT Angiography. J Clin Med. 2022;11(19):5500. doi:10.3390/jcm11195500

4. Egbe AC, Ananthaneni S, Jadav R, et al. Coronary artery disease in adults with tetralogy of Fallot. Congenit Heart Dis. 2019;14(4):491-497. doi:10.1111/chd.12782

5. Waldmann V, Combes N, Ladouceur M, et al. Understanding electrocardiography in adult patients with congenital heart disease: A review. JAMA Cardiol. 2020;5;(12):1435-1444. doi:10.1001/jamacardio.2020.3416

6. Leonardi B, Gentili F, Perrone MA, et al. Cardiopulmonary Exercise Testing in Repaired Tetralogy of Fallot: Multiparametric Overview and Correlation with Cardiac Magnetic Resonance and Physical Activity Level. J Cardiovasc Dev Dis. 2022;9(1):26. doi:10.3390/jcdd9010026