Abstract Body (Do not enter title and authors here): Background: The management of coronary artery anomalies (CAA) remains a clinical dilemma as the prognostic implications are poorly understood. The presence of ischemia and CAA does not establish causality. We report the first documented case of hereditary transthyretin cardiac amyloidosis (ATTR-CA) in a patient with CAA, highlighting the diagnostic and therapeutic complexity of this dual pathology.
Case: A 65-year-old man with a history of carpal tunnel syndrome, hypertension, and CAA presented with exertional dyspnea. Family history included a brother with hypertrophic cardiomyopathy. Stress testing noted ischemia in the left anterior descending (LAD) and left circumflex (LCX) territories. Invasive angiography and cardiac computed tomography (CT) confirmed an anomalous LAD arising from the right coronary cusp with an interarterial course and a retroaortic LCX arising from the ostium of the right coronary artery without obstructive disease (Figure 1). Echocardiography revealed concentric LV thickening, severe diastolic dysfunction, an apical sparing strain pattern, and dynamic left ventricular outflow tract obstruction (Figure 2). Light-chain amyloidosis was excluded, and cardiac scintigraphy confirmed ATTR-CA (Figure 3). Genetic testing revealed a rare TTR variant of previously uncertain significance (p.Val113Leu), prompting cascade screening.
Discussion: The diagnosis of ATTR-CA reframed the patient’s ischemia and prompted reevaluation of the family’s cardiac history. ATTR-CA likely contributed to ischemia through microvascular dysfunction and supply-demand mismatch rather than epicardial coronary obstruction. Surgical reimplantation of CAA was deferred in favor of aggressive medical management resulting in symptomatic improvement. Subsequent testing of the patient’s sibling identified ATTR-CA with the same mutation (p.Val113Leu), supporting reclassification of the variant as likely pathogenic.
Conclusion: This case underscores the importance of an integrated anatomic and functional assessment of ischemia in patients with CAA. The presence of infiltrative disease, specifically ATTR-CA, may amplify the ischemic potential of CAA. Furthermore, the identification of ATTR-CA redefined a presumed familial diagnosis and provides compelling evidence supporting reclassification of the rare TTR genetic variant (p.Val113Leu) as likely pathogenic. This finding carries significant implications for genetic counseling and management strategies of affected families.