NSTE-ACS at the Emergency: Can You Guess What is Under the Umbrella?

Keywords:
Acute Coronary Syndrome; Non-ST Elevated Myocardial Infarction; Biomarkers; Myocardial Ischemia; Troponin; Electrocardiography/methods

The reasoning behind the often-difficult task of deciding whether, when and how to treat the patient with established Cardiovascular Disease (CVD) might be based on two simple questions: (1) Are we treating an acute event?, and (2) What is my patient at risk of in the future? Whilst the first question implies an expedite straightforward treatment, the second premise depends mostly on risk stratification and, thus, the capability of one to anticipate the likelihood of an event.11. Collet JP, Thiele H, Barbato E, Barthelemy O, Bauersachs J, Bhatt DL, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST elevation The Task Force for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2021 Apr 7;42(14):1289-367. Withal, the physician often encounters a scenario in which the two questions must be addressed altogether. Accordingly, the response is more likely one of a probability rather than a categorical (yes or no) answer. This is the outline in umbrella diagnoses, as is non-ST segment elevation (NSTE) Acute Coronary Syndromes (ACS).22. George B, Misumida N, Ziada KM, George B. Revascularization Strategies for Non-ST-Elevation Myocardial Infarction. Curr Cardiol Rep. 2019 Apr 10;21(5):39.,33. Feldman L, Steg PG, Amsallem M, Puymirat E, Sorbets E, ElbazM, et al. Medically managed patients with non – ST-elevation acute myocardial infarction have heterogeneous outcomes, based on performance of angiography and extent of coronary artery disease. Eur Heart J Acute Cardiovasc Care. 2017;6(3):262-71.

There are a multitude of clinical tools in Cardiovascular Medicine44. Ascenzo F, Biondi-Zoccai G, Moretti C, Boliati M, Ameda P, Sciuto F, et al. TIMI, GRACE and alternative risk scores in Acute Coronary Syndromes: A meta-analysis of 40 derivation studies on 216, 552 patients and of 42 validation studies on 31, 625 patients. Contemp Clin Trials. 2012 May;33(3):507-14.66. Torralba F, Navarro A, Hoz JC, la Hoz JC, Ortiz C, Botero A, et al. HEART, TIMI, and GRACE Scores for Prediction of 30-Day Major Adverse Cardiovascular Events in the Era of High-Sensitivity Troponin. Arq Bras Cardiol. 2020 Mar 13;114(5):795-802. that aid physicians in the decision-making process, often surpassing the “educated guess” in acute settings.77. Fanaroff AC, Rymer JA, Goldstei, SA, Simel DL. Does This Patient With Chest Pain Have Acute Coronary Syndrome ? The Rational Clinical Examination Systematic Review. JAMA. 2015 Nov 10;314(18):1955-65.,88. Oliver G, Reynard C, Morris N, Body R. Can Emergency Physician Gestalt “ Rule In ” or “ Rule Out ” Acute Coronary Syndrome: Validation in a Multicenter Prospective Diagnostic Cohort Study. Acad Emerg Med. 2020 Jan;27(1):24-30. However, the use of these tools in NSTE-ACS is particularly challenging for a number of reasons:

Firstly, is this really NSTE-ACS? The diagnosis requires the combination of a cardiac biomarker variation over time with either myocardial ischemic symptoms or new ischemic ECG findings, or imaging of loss of viable myocardium or new regional wall motion abnormality with an ischemic pattern.11. Collet JP, Thiele H, Barbato E, Barthelemy O, Bauersachs J, Bhatt DL, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST elevation The Task Force for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2021 Apr 7;42(14):1289-367. Importantly, high-sensitivity cardiac troponins have facilitated the identification of NSTE Myocardial Infarction [particularly by reducing the likelihood of a missed “unstable angina” (UA) with previous biomarkers] but have somewhat complicated its differential diagnosis – stressing the scenario in which one must consider the more-inclusive myocardial injury term.11. Collet JP, Thiele H, Barbato E, Barthelemy O, Bauersachs J, Bhatt DL, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST elevation The Task Force for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2021 Apr 7;42(14):1289-367.,99. Thygesen T, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth universal definition of myocardial infarction Eur Heart J. 2019;40(3):237-69. Furthermore, symptoms and ECG changes might be attributable to non-ischemic mechanisms, thus translating into their mediocre specificity.99. Thygesen T, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth universal definition of myocardial infarction Eur Heart J. 2019;40(3):237-69.,1010. Carlton EW, Pickering JW, Greenslade J, Cullen L, Than M, Kendall J, et al. Assessment of the 2016 National Institute for Health and Care Excellence high-sensitivity troponin rule-out strategy. Heart. 2018 Apr; 104(8): 665–72.

Secondly, how severe is the underlying disease causing NSTE-ACS? Even when considering type-1 (spontaneous, atherosclerosis-related) Myocardial Infarction,99. Thygesen T, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth universal definition of myocardial infarction Eur Heart J. 2019;40(3):237-69. the spectrum of coronary artery disease (CAD) may consist of single-vessel and/or distal stenosis vs. more complex severe proximal and/or three-vessel disease. The plot further thickens if one considers additional pathophysiological mechanisms that can be at work1111. Safdar B, Spatz E, Dreyer RP, Beltrame JF, Lichtman JH, Spertus JA, et al. Presentation, Clinical Profile, and Prognosis of Young Patients With Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA): Results From the VIRGO Study. (2018). J Am Heart Assoc. 2018;7(13):e009174. – the so-called type-2 Myocardial Infarction.99. Thygesen T, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth universal definition of myocardial infarction Eur Heart J. 2019;40(3):237-69. In these cases, notably, CAD might be present merely as a confounding bystander.

Finally, how should I treat this patient with NSTE-ACS? The decision should be based on clinical characteristics and CAD severity. It may involve a conservative approach or myocardial revascularization,11. Collet JP, Thiele H, Barbato E, Barthelemy O, Bauersachs J, Bhatt DL, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST elevation The Task Force for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2021 Apr 7;42(14):1289-367. by means of a percutaneous coronary intervention and/or coronary artery bypass grafting (CABG). However, the latter has not been incorporated into score systems but surely influences prognosis.1212. Smilowitz NR, Mahajan AM, Roe MT, Helikamp AS, Criswell K, Gulati M, et al. Mortality of Myocardial Infarction by Sex, Age, and Obstructive Coronary Artery Disease Status in the ACTION Registry – GWTG (Acute Coronary Treatment and Intervention Outcomes Network Registry – Get With the Guidelines). Circ Cardiovasc Qual Outcomes. 2017 Dec;10(12):e003443.,1313. Menozzi A, Servi S, Rossini R, Ferlini M, Lina D, Abrignani MG, et al. Patients with non-ST segment elevation acute coronary syndromes managed without coronary revascularization: A population needing treatment improvement. Int J Cardiol. 2017 245:35-42.

Cedro et al. present an article where clinical scores (TIMI, GRACE and HEART) were used to predict the complexity of the underlying CAD, as per the SYNTAX score. To do so, the authors designed an observational study enrolling 138 patients with NSTE-ACS (with a mean age of 60 ± 11 years, of whom 68% were males, and often presenting with traditional cardiovascular risk factors). Most had UA (67,3%) and the spectrum of CAD severity was broad, as one may infer from the inclusion of patients with multi-vessel disease (53,7%) or absence of significant (>50%) coronary stenosis (29,7%). The authors have found that the correlations between the clinical and SYNTAX scores were moderate at best. Nonetheless, the HEART score performed particularly well in predicting complex CAD (i.e., SYNTAX >32, with an area under the curve of 0.81). Interestingly, a cut-off value of >4 and ≥140 for HEART and GRACE scores yielded a sensitivity and specificity of 100% and 97%, respectively, to predict such severe CAD.1414. Cedro AV, Mota DM, Ohe LN, Timerman A, Costa JR, Castro LS. Association between Clinical Risk Score (Heart, Grace and TIMI) and Angiographic Complexity in Acute Coronary Syndrome without ST Segment Elevation. Arq Bras Cardiol. 2021; 117(2):281-287. doi: https://doi.org/10.36660/abc.20190417
https://doi.org/10.36660/abc.20190417...

Given the abovementioned results, it is proposed that the combined use of the HEART and GRACE scores might be useful in detecting complex CAD.1414. Cedro AV, Mota DM, Ohe LN, Timerman A, Costa JR, Castro LS. Association between Clinical Risk Score (Heart, Grace and TIMI) and Angiographic Complexity in Acute Coronary Syndrome without ST Segment Elevation. Arq Bras Cardiol. 2021; 117(2):281-287. doi: https://doi.org/10.36660/abc.20190417
https://doi.org/10.36660/abc.20190417...
It should be noted, however, that this is a small exploratory single-center study, mostly including patients with UA (in whom the GRACE score has not been extensively validated, as far as prognosis is concerned). Nonetheless, it would be an alluring hypothesis to investigate whether these scores might be incorporated as a valid tool in the pathway of care of NSTE-ACS patients, namely: (1) Could these be used as a novel criterion for immediate invasive strategy listing?, and (2) Could these differentiate between patients in whom P2Y12 pre-treatment strategy is safe and desirable from those in whom it might cause harm (e.g. potentially delaying CABG)?

In conclusion, the preliminary findings of this study suggest an interesting concept: rather than using the usual clinical tools to predict the risk of outcomes, we might want to use them to determine whether there might be a severe complex condition underlying CAD, warranting surgical revascularization.1515. Yildirim A, Kucukosmanoglu M, Yavuz F, Koyunsever NY, Cekici Y, Dogdus M, et al. Comparison of the ATRIA, CHA2DS2-VASc, and Modified Scores ATRIA-HSV, CHA2DS2-VASc-HS, for the Prediction of Coronary Artery Disease Severity. Angiology. 2021;Feb 08;3319721991410. Whether these multivariate risk prediction model tools might improve outcomes remains unclear, yet this hypothesis is worth being prospectively investigated. The presented work adds a small but important piece supporting this rationale, unveiling what might be truly under the umbrella.

  • Short Editorial related to the article: Association between Clinical Risk Score (Heart, Grace and TIMI) and Angiographic Complexity in Acute Coronary Syndrome without ST Segment Elevation

References

  • 1
    Collet JP, Thiele H, Barbato E, Barthelemy O, Bauersachs J, Bhatt DL, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST elevation The Task Force for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2021 Apr 7;42(14):1289-367.
  • 2
    George B, Misumida N, Ziada KM, George B. Revascularization Strategies for Non-ST-Elevation Myocardial Infarction. Curr Cardiol Rep. 2019 Apr 10;21(5):39.
  • 3
    Feldman L, Steg PG, Amsallem M, Puymirat E, Sorbets E, ElbazM, et al. Medically managed patients with non – ST-elevation acute myocardial infarction have heterogeneous outcomes, based on performance of angiography and extent of coronary artery disease. Eur Heart J Acute Cardiovasc Care. 2017;6(3):262-71.
  • 4
    Ascenzo F, Biondi-Zoccai G, Moretti C, Boliati M, Ameda P, Sciuto F, et al. TIMI, GRACE and alternative risk scores in Acute Coronary Syndromes: A meta-analysis of 40 derivation studies on 216, 552 patients and of 42 validation studies on 31, 625 patients. Contemp Clin Trials. 2012 May;33(3):507-14.
  • 5
    Cortés M, Haseeb S, Lambardi F,Arbucci R, Ariznovarreta P, Resi S, et al. The HEART score in the era of the European Society of Cardiology 0 / 1-hour algorithm. Eur Heart J Acute Cardiovasc Care. 2020 Feb;9(1):30-8.
  • 6
    Torralba F, Navarro A, Hoz JC, la Hoz JC, Ortiz C, Botero A, et al. HEART, TIMI, and GRACE Scores for Prediction of 30-Day Major Adverse Cardiovascular Events in the Era of High-Sensitivity Troponin. Arq Bras Cardiol. 2020 Mar 13;114(5):795-802.
  • 7
    Fanaroff AC, Rymer JA, Goldstei, SA, Simel DL. Does This Patient With Chest Pain Have Acute Coronary Syndrome ? The Rational Clinical Examination Systematic Review. JAMA. 2015 Nov 10;314(18):1955-65.
  • 8
    Oliver G, Reynard C, Morris N, Body R. Can Emergency Physician Gestalt “ Rule In ” or “ Rule Out ” Acute Coronary Syndrome: Validation in a Multicenter Prospective Diagnostic Cohort Study. Acad Emerg Med. 2020 Jan;27(1):24-30.
  • 9
    Thygesen T, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth universal definition of myocardial infarction Eur Heart J. 2019;40(3):237-69.
  • 10
    Carlton EW, Pickering JW, Greenslade J, Cullen L, Than M, Kendall J, et al. Assessment of the 2016 National Institute for Health and Care Excellence high-sensitivity troponin rule-out strategy. Heart. 2018 Apr; 104(8): 665–72.
  • 11
    Safdar B, Spatz E, Dreyer RP, Beltrame JF, Lichtman JH, Spertus JA, et al. Presentation, Clinical Profile, and Prognosis of Young Patients With Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA): Results From the VIRGO Study. (2018). J Am Heart Assoc. 2018;7(13):e009174.
  • 12
    Smilowitz NR, Mahajan AM, Roe MT, Helikamp AS, Criswell K, Gulati M, et al. Mortality of Myocardial Infarction by Sex, Age, and Obstructive Coronary Artery Disease Status in the ACTION Registry – GWTG (Acute Coronary Treatment and Intervention Outcomes Network Registry – Get With the Guidelines). Circ Cardiovasc Qual Outcomes. 2017 Dec;10(12):e003443.
  • 13
    Menozzi A, Servi S, Rossini R, Ferlini M, Lina D, Abrignani MG, et al. Patients with non-ST segment elevation acute coronary syndromes managed without coronary revascularization: A population needing treatment improvement. Int J Cardiol. 2017 245:35-42.
  • 14
    Cedro AV, Mota DM, Ohe LN, Timerman A, Costa JR, Castro LS. Association between Clinical Risk Score (Heart, Grace and TIMI) and Angiographic Complexity in Acute Coronary Syndrome without ST Segment Elevation. Arq Bras Cardiol. 2021; 117(2):281-287. doi: https://doi.org/10.36660/abc.20190417
    » https://doi.org/10.36660/abc.20190417
  • 15
    Yildirim A, Kucukosmanoglu M, Yavuz F, Koyunsever NY, Cekici Y, Dogdus M, et al. Comparison of the ATRIA, CHA2DS2-VASc, and Modified Scores ATRIA-HSV, CHA2DS2-VASc-HS, for the Prediction of Coronary Artery Disease Severity. Angiology. 2021;Feb 08;3319721991410.

Publication Dates

  • Publication in this collection
    06 Sept 2021
  • Date of issue
    Aug 2021
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