It is often said that there is no pain greater than the pain of a broken heart, and believe it or not, it is medically possible to suffer and die of a broken heart. As a result of severe emotional or physical stress, the left ventricle, the heart’s main pumping chamber, can weaken, causing decreased blood circulation and even severe hemodynamic compromise. This condition, known as Takotsubo cardiomyopathy (TTC) has a fitting nickname: Broken Heart Syndrome (2). The danger of Broken Heart Syndrome lies in the reality that its symptoms are indistinguishable from those of a myocardial infarction (heart attack), since electrocardiogram (EKG) readings of TTC may fluctuate similarly - displaying matching ST-segment elevation - to those found in a heart attack. Hence, in the acute emergency setting, TTC is heavily misdiagnosed as an acute myocardial infarction (AMI), resulting in disease mismanagement and further hemodynamic compromise (3). Recent research has begun to shed light on how we can improve diagnostic testing for takotsubo cardiomyopathy, most prominently with the use of circulating cardiac biomarkers (1, 4).
In a study to improve diagnostic testing for TTC led by Milosz Jaguszewski, et. al, researchers identified a signature of four microRNAs that differentiated between TTC and an AMI based on differing levels of expression (1). Using a reverse transcription polymerase chain reaction, the researchers selected eight microRNAs for testing in 36 TTC patients, 27 AMI patients, and 28 healthy subjects as controls. Centrifugation of blood samples and expression analysis elucidated that a unique signature of four circulating microRNAs– miR-1, miR-16, miR-26a, and miR-133a– differentiated TTC from healthy subjects. Moreover, miR-133a was substantially increased in patients with AMI compared with TTC (1).
Additionally, further research is being done to explore protein expression as an aid in differentiating diagnosis of takotsubo cardiomyopathy. It is projected that in supplement to current TTC diagnostic guidelines, Endothelin-1 and Troponin– two cardiac proteins– will demonstrate varying expression levels, just as shown with microRNA expression. In an effort to incorporate protein expression into diagnostic testing, an “International Expert Consensus” was published in 2018, updating diagnostic criteria to place an emphasis on myocardial changes otherwise overlooked by physicians: a presence of coronary artery disease (CAD) and neurologic disorders, among other non contradictions.
Ultimately, the aforementioned biomarker research aims to ameliorate diagnostic testing for takotsubo cardiomyopathy and aid in the preemptive treatment of TTC, allowing physicians to accurately address left ventricular dysfunction in the emergency setting. By decreasing high levels of TTC misdiagnosis, scientists continue to heal broken hearts, lending the amelioration of diagnostic testing to other cardiac, pulmonary, and neurologic conditions in the near future.
References:
- Jaguszewski, M., et al. "A Signature of Circulating microRNAs Differentiates Takotsubo Cardiomyopathy from Acute Myocardial Infarction." European Heart Journal, no. 35, 17 Sept. 2013, pp. 999-1006.
- Harvard Health Publishing. “Takotsubo Cardiomyopathy (Broken-Heart Syndrome).” Harvard Health, www.health.harvard.edu/heart-health/takotsubo-cardiomyopathy-broken-heart-syndrome.
- Vyas, C., et al. “Consequences of Misdiagnosis and Mismanagement of Takotsubo Cardiomyopathy.” Acute Cardiac Care, no.14, 2012, pp. 117-119. Retrieved from https://www.tandfonline.com/doi/full/10.3109/17482941.2012.735674
- Randhawa, M., et al. “Diagnostic Utility of Cardiac Biomarkers in Discriminating Takotsubo Cardiomyopathy from Acute Myocardial Infarction.” Journal of Cardiac Failure, no. 20, 2014, pp. 2-8.
Ghadri, J, et. al., “International Expert Consensus Document on Takotsubo Cardiomyopathy (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology” European Heart Journal, no. 39, 07 June 2018, pp. 2032–2046.