Chromogranin-A Levels Differentiate Takotsubo From Acute Coronary Syndrome And Congestive Heart Failure In Women: A Single-Center Case-Control Study

Background: Takotsubo syndrome (TTS) has been reported in up to 10% of women with a clinical presentation suggestive of acute coronary syndrome (ACS), making the differential diagnosis challenging. Chromogranin-A (CgA) is a pro-hormone co-released with catecholamines. Elevated levels of CgA are found in ACS and in exacerbations of congestive heart failure (CHF), indicating an imbalance of the neuroendocrine system. Hypothesis: CgA levels in women with TTS might differ from levels in other conditions featuring acute heart failure. Methods: We systematically screened CgA levels in 54 consecutive women admitted with TTS (n=29) or either CHF exacerbation or ACS (n=25) between November 2016 and September 2019. Clinical parameters including left ventricle ejection fraction, in-hospital events, troponin I (TnI), creatinine, and natriuretic peptide type B (NT-pro-BNP) values were recorded. Only samples obtained within 24 hours from symptom onset were analyzed. We excluded 18 subjects with TTS and 6 with ACS/CHF because of a history of cancer, chronic kidney disease >III stage, liver cirrhosis, or autoimmune disease. Results: Patients with TTS (Group 1, n=11) were compared with patients with ACS/CHF (Group 2, n=19). Subjects in Group 1 were significantly younger (mean age 67 vs 80, p<0.01) and presented with remarkably lower levels of CgA compared to Group 2 (1.57 nMol/l, IQR 0.56-4.6 vs 7.46, IQR 1.1-17.15, normal value <3 nMol/l, p<0.002), even adjusting for confounders such as the use of proton pump inhibitors, hypertension, and renal function. When controlling for age, there was a significant association between being in Group 2 and higher mean levels of CgA (p<0.03). At ROC curve analysis, CgA was the best predictor of TTS vs ACS/CHF when compared with TnI and NT-pro-BNP levels (AUC 0.85, 95% C.I. 0.72-0.98; 0.59, 95% C.I. 0.31-0.86; 0.5, 95% C.I. 0.28-0.72, respectively). CgA levels <5.32 could discriminate TTS from ACS/CHF with positive and negative predictive values of 22 and 100% respectively (accuracy 68%). Conclusion: In our population, systemic CgA levels collected within 24 hours from symptom onset were significantly lower in women with TTS compared to ACS/CHF, possibly indicating a different acute neuroendocrine pattern.