Elevated Thiol Levels: A New Marker of Ventricular Arrhythmias in Acute Coronary Syndrome?

Keywords
Sulfhydryl Compounds; Arrhythmias, Cardiac; Acute Coronary Syndrome

Ventricular arrhythmias in patients with acute coronary syndrome are not frequent, but they lead to a greater occurrence of complications and death.^1,2 Its prevalence is higher in infarction with ST-segment elevation (STEMI) and has a worse prognosis when it occurs 48 hours after admission.³ Thus, a marker capable of predicting the occurrence of these events is welcome.

Three mechanisms justify the occurrence of arrhythmias in the acute phase of the infarction:

• Injured myocardium can be a substrate for the development of reentry circuits or a focus of increased automaticity;

• Triggering of arrhythmias secondary to heart rate variation;

• Modulating factors, such as electrolyte disturbances, autonomic dysfunction, persistent ischemia, or reduced left ventricular function.

Thus, the identification of markers that influence these mechanisms can be the key to a new predictor. Thiols have antioxidant activity and, during oxidative processes, they can be transformed into different molecules, such as thiol-disulfide⁴. Studies have already shown that the thiol-disulfide ratio is a promising marker of oxidative stress.^5,6

Erdoğan et al. studied the association between plasma thiol parameters and troponin levels in patients with acute coronary syndrome (ACS) and the prediction of in-hospital ventricular arrhythmia.⁷

A total of 191 patients diagnosed with ACS were studied, subdivided into ACS without ST-segment elevation (SCA-SSDST) and with ST-segment elevation (SCA-SDST). In addition to the dosage of native thiol, disulfide, and the thiol-disulfide ratio, other parameters were evaluated, both in a univariate model and in the logistic regression model, such as LDL, age, LVEF, serum potassium, and magnesium levels, neutrophil-lymphocyte ratio (RNL), time to hospitalization, troponin/native thiol ratio (RTTN), and troponin.

There was no difference in plasma thiol levels (native or total), disulfide, native disulfide-thiol ratio, total disulfide-thiol ratio, and native thiol-total thiol ratio when comparing SCA-SSDST and SCA-SDST, demonstrating that both diagnoses are similar in terms of the degree of oxidative stress. Likewise, no difference was found regarding the occurrence of ventricular arrhythmias.

In the analysis of correlation of multiple variables with oxidative stress parameters, many showed significant results, but with weak or moderate correlation. The best correlation was observed with the CK-MB mass dosage with the troponin-native thiol ratio (r=0.63; p<0.001), probably due to the correlation of this biomarker with troponin.

Finally, logistic regression to predict ventricular arrhythmias was performed in three scenarios: SCA-SSDST, SCA-SDST, and the entire population. In SCA-SDST, native thiol was an independent predictor, while RTTN was a predictor in SCA-SSDST. In the entire ACS population, both markers (native thiol and RTTN) were the predictor variables. A greater emphasis was given to the RTTN, which presented a good area under the curve (AUC=0.783), with good specificity and sensitivity for predicting ventricular arrhythmias.

This is the first study to demonstrate the correlation of oxidative stress markers with ventricular arrhythmias, highlighting RTTN. The main marker currently known is the area of myocardial damage, documented through the ejection fraction.⁸ Patients with reduced ejection fraction deserve special attention regarding the need for implantable defibrillators, due to the risk of ventricular arrhythmias.

Troponin levels directly influence RTTN and may demonstrate greater myocardial damage and, therefore, greater risk of ventricular arrhythmias. The present study does not present the ROC curve for native thiol, although it was also considered a marker in logistic regression, limiting the evaluation of this marker. We know that troponin is an important prognostic marker in patients with SCA⁹ and has a correlation with the area of myocardial damage.

On the other hand, this and other studies have shown a correlation between thiol levels and severity (GRACE score), including the occurrence of adverse events.¹⁰ Furthermore, Rajic D et al. demonstrated that the serum thiol level was an independent predictor of infarction-related complications, especially ventricular dysfunction.¹¹ Thus, the question arises whether thiol is an independent predictor of ventricular arrhythmia or another marker of ventricular damage and dysfunction.

Serum thiol dosage is not part of the routine evaluation of a patient with ACS. Therefore, broader studies are needed to assess the real impact of incorporating this technology in the management of these patients.

• Short Editorial related to the article: Association between Plasma Thiol Parameters and Troponin Levels in Patients with Acute Coronary Syndrome and Prediction of In-Hospital Ventricular Arrhythmia

Referências

• ¹
  Newby KH, Thompson T, Stebbins A, Topol EJ, Califf RM, Natale A. Sustained Ventricular Arrhythmias in Patients Receiving Thrombolytic Therapy: Incidence and Outcomes. The GUSTO Investigators. Circulation. 1998;98(23):2567-73. doi: 10.1161/01.cir.98.23.2567.
  » https://doi.org/10.1161/01.cir.98.23.2567
• ²
  Gorenek B, Lundqvist CB, Terradellas JB, Camm AJ, Hindricks G, Huber K, et al. Cardiac Arrhythmias in Acute Coronary Syndromes: Position Paper from the Joint EHRA, ACCA, and EAPCI TASK Force. Europace. 2014;16(11):1655-73. doi: 10.1093/europace/euu208.
  » https://doi.org/10.1093/europace/euu208
• ³
  Orvin K, Eisen A, Goldenberg I, Gottlieb S, Kornowski R, Matetzky S, et al. Outcome of Contemporary Acute Coronary Syndrome Complicated by Ventricular Tachyarrhythmias. Europace. 2016;18(2):219-26. doi: 10.1093/europace/euv027.
  » https://doi.org/10.1093/europace/euv027
• ⁴
  Korkmaz A, Doğanay B, Basyigit F, Çöteli C, Yildiz A, Gursoy T, et al. Serum Thiol Levels and Thiol/Disulfide Homeostasis in Patients with Rheumatic Mitral Valve Disease and Healthy Subjects. Arq Bras Cardiol. 2021:S0066-782X2021005009203. doi: 10.36660/abc.20200161.
  » https://doi.org/10.36660/abc.20200161
• ⁵
  Kundi H, Ates I, Kiziltunc E, Cetin M, Cicekcioglu H, Neselioglu S, et al. A Novel Oxidative Stress Marker in Acute Myocardial Infarction; Thiol/Disulphide Homeostasis. Am J Emerg Med. 2015;33(11):1567-71. doi: 10.1016/j.ajem.2015.06.016.
  » https://doi.org/10.1016/j.ajem.2015.06.016
• ⁶
  Kızıltunç E, Gök M, Kundi H, Çetin M, Topçuoğlu C, Gülkan B, et al. Plasma Thiols and Thiol-Disulfide Homeostasis in Patients with Isolated Coronary Artery Ectasia. Atherosclerosis. 2016;253:209-13. doi: 10.1016/j.atherosclerosis.2016.07.904.
  » https://doi.org/10.1016/j.atherosclerosis.2016.07.904
• ⁷
  Erdoğan M, Ozturk S, Tutar EÖ, Arslan E, Çelik MC, Baştuğ S, et al. Association between Plasma Thiol Parameters and Troponin Levels in Patients with Acute Coronary Syndrome and Prediction of In-Hospital Ventricular Arrhythmia. Arq Bras Cardiol. 2021; 117(3):465-473. doi: 10.36660/abc.20190672.
  » https://doi.org/10.36660/abc.20190672
• ⁸
  Bhar-Amato J, Davies W, Agarwal S. Ventricular Arrhythmia after Acute Myocardial Infarction: ‘The Perfect Storm’. Arrhythm Electrophysiol Rev. 2017;6(3):134-9. doi: 10.15420/aer.2017.24.1.
  » https://doi.org/10.15420/aer.2017.24.1
• ⁹
  Castro LT, Santos IS, Goulart AC, Pereira AC, Staniak HL, Bittencourt MS, et al. A Troponina I de Alta Sensibilidade Elevada na Fase Estabilizada após Síndrome Coronariana Aguda prevê Mortalidade por todas as causas e Mortalidade Cardiovascular em uma População Altamente Miscigenada: uma Coorte de 7 Anos. Arq. Bras. Cardiol. 2019;112(3):230-7. doi: 10.5935/abc.20180268.
  » https://doi.org/10.5935/abc.20180268
• ¹⁰
  Sivri S, Kasapkara HA, Polat M, Alsancak Y, Durmaz T, Erel Ö, et al. Dynamic Thiol/Disulphide Homeostasis and its Prognostic Value in Patients with Non-ST Elevation-Acute Coronary Syndromes. Kardiol Pol. 2018;76(2):426-32. doi: 10.5603/KP.a2017.0208.
  » https://doi.org/10.5603/KP.a2017.0208
• ¹¹
  Rajic D, Jeremic I, Stankovic S, Djuric O, Zivanovic-Radnic T, Mrdovic I, et al. Oxidative Stress Markers Predict Early Left Ventricular Systolic Dysfunction After Acute Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention. Adv Clin Exp Med. 2018;27(2):185-91. doi: 10.17219/acem/64464.
  » https://doi.org/10.17219/acem/64464

Publication Dates

• Publication in this collection
  20 Sept 2021
• Date of issue
  Sept 2021