The Role of Cardiac Biomarkers in Evaluating Takotsubo Cardiomyopathy: A Systematic Review

Abstract

Takotsubo cardiomyopathy (TTS) is an acute, reversible cardiac condition marked by transient wall motion abnormalities of the left ventricle, typically triggered by intense emotional or physical stress. Despite being first described in 1990, TTS remains relatively obscure due to limited understanding of its pathophysiology. Clinically, it mimics acute coronary syndrome (ACS), presenting with symptoms such as chest pain, shortness of breath, and ECG changes like ST-segment deviations. This resemblance often leads to initial misdiagnosis and treatment with antiplatelet and anticoagulant therapy - interventions that lack proven efficacy in managing TTS. Given the diagnostic challenges posed by the clinical overlap between TTS and ACS and the absence of disease-specific diagnostic markers, several researchers have investigated the potential role of cardiac biomarkers in distinguishing between the two conditions. This systematic review aims to explore the diagnostic utility of cardiac biomarkers in evaluating TTS. We conducted a systematic literature search using PubMed and Google Scholar, focusing on studies published between 2013 and August 10, 2023. Inclusion criteria were limited to human studies published in English with freely available full texts that evaluated the diagnostic performance of cardiac biomarkers in TTS. A total of eight studies met the criteria and were included for in-depth analysis. These studies examined a range of biomarkers, including established ones such as troponin, B-type natriuretic peptide (BNP), N-terminal proBNP, and creatine kinase-myocardial band (CK-MB), as well as emerging markers like copeptin and microRNAs (miRNAs). Collectively, the studies analyzed data from 3,602 individuals. Troponin showed limited diagnostic accuracy in differentiating TTS from ACS. In contrast, BNP exhibited stronger discriminatory ability, both alone and when used in combination with other markers. The combined use of BNP, troponin, and CK-MB enhanced diagnostic performance. Furthermore, emerging biomarkers such as copeptin and miRNAs demonstrated promising potential due to their early release patterns, association with stress-response mechanisms, and distinct expression profiles, offering new avenues for improving diagnostic accuracy. This review underscores the potential diagnostic value of both established and emerging cardiac biomarkers in identifying TTS. The findings support further research into novel biomarkers, which may ultimately lead to earlier and more accurate diagnosis, reduce inappropriate treatment, and enable more targeted and timely clinical interventions.

Keywords: apical ballooning syndrome; biomarkers; broken heart syndrome; stress cardiomyopathy; takotsubo cardiomyopathy.

Figure 1. Diagnostic algorithm for TTS (adapted from the 2018 InterTAK consensus statement)

CAD: coronary artery disease; CAG: coronary angiography; CCTA: coronary computed tomography angiography; CMR: cardiac magnetic resonance imaging; TTE: transthoracic echocardiography; TTS: Takotsubo cardiomyopathy; WM: wall motion Adapted from Ghadri et al. (2018) [6]

Figure 2. PRISMA flow diagram illustrating the search strategy and study selection process for the systematic review

PRISMA: Preferred Reporting Items for Systematic reviews and Meta-Analyses