Chest pain in cardiac amyloidosis: occurrence, causes and prognostic significance

Background: Chest pain is experienced by patients with cardiac amyloidosis (CA), but a systematic investigation of its frequency, underlying etiologies and clinical significance is lacking. Methods: Clinical, echocardiographic, laboratory characteristics, available coronary arteries imaging and endomyocardial biopsy (EMB) findings of 174 patients with CA (n = 104 with transthyretin, ATTR; n = 70 with light chains, AL) were analyzed. Results: Chest pain was reported in 66 (38%) CA patients. Compared to those without, patients with chest pain had more frequently a history of coronary artery disease (CAD) (27% vs 15%, p = 0.048) and heart failure (HF) symptoms (62% vs 43%, p = 0.015), higher high sensitivity troponin I (hs-cTnI, 101 vs 65 ng/L, p = 0.032) and higher brain natriuretic peptide (597 vs 407 ng/L, p = 0.024). Among CA patients with chest pain undergoing coronary arteries imaging (n = 37), obstructive CAD was detected in 14 (38%), 13 of whom with ATTR-CA. Of these 37 patients, EMB was available in 10 and vascular/perivascular amyloid deposition was detected in 4/5 (80%) of AL-CA patients and 1/5 ATTR-CA. Among patients with suspected acute coronary syndrome (n = 22), obstructive CAD was detected in 9/17 (53%) ATTR-CA and 0/5 AL-CA; hs-cTnI levels were similar between those with and without obstructive CAD. During a follow-up of 17 (8-34) months, chest pain was a significant predictor of HF hospitalization (HR1.86, 95% CI 1.02-3.39, p = 0.042), even after adjustment for CA subtype and CAD. Conclusion: Chest pain is a common symptom in patients with CA, reflects a more advanced cardiac impairment and predicts future HF hospitalization. The etiology of chest pain seems to differ, with obstructive CAD more frequent in ATTR-CA whilst amyloid vascular/perivascular involvement more common in AL-CA.