Diagnostic and Management Dilemmas in Women Presenting with Acute Coronary Syndromes

Abstract

Purpose of Review

To summarize gender- and sex-specific differences in the presentation, diagnosis, management, and pathophysiology of women presenting with acute coronary syndrome (ACS).

Recent Findings

Sex differences exist in many aspects of ACS that impact the identification, treatment, and outcomes in women. There are delays in the initiation of care, under recognized diagnostic differences based on sex, and inconsistencies in the management of ACS in women compared with men, that ultimately impact outcomes. Additionally, women with ACS are more likely than men to present with non-obstructive coronary artery disease (CAD), which appears to be due to diverse underlying pathophysiology.

Summary

Women with ACS face diagnostic and treatment dilemmas from time of symptom onset to hospital discharge. Under-recognition, under-diagnosis, and under-treatment ultimately result in poorer outcomes in women. Underlying pathophysiologic differences in women require additional testing to elucidate underlying etiologies.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.

    Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, et al. Heart disease and stroke statistics-2020 update: a report from the American Heart Association. Circulation. 2020;141(9):e139–596.

    PubMed  Article  PubMed Central  Google Scholar 

  2. 2.

    •• Stehli J, Martin C, Brennan A, Dinh DT, Lefkovits J, Zaman S. Sex differences persist in time to presentation, revascularization, and mortality in myocardial infarction treated with percutaneous coronary intervention. J Am Heart Assoc. 2019;8(10):e012161 Important study of AMI patients showing women with STEMI have significant delays in revascularization contributing to higher mortality rates compared to men.

    PubMed  PubMed Central  Article  Google Scholar 

  3. 3.

    Heer T, Hochadel M, Schmidt K, Mehilli J, Zahn R, Kuck KH, et al. Sex differences in percutaneous coronary intervention-insights from the coronary angiography and PCI Registry of the German Society of Cardiology. J Am Heart Assoc. 2017;6(3).

  4. 4.

    Pelletier R, Humphries KH, Shimony A, Bacon SL, Lavoie KL, Rabi D, et al. Sex-related differences in access to care among patients with premature acute coronary syndrome. CMAJ. 2014;186(7):497–504.

    PubMed  PubMed Central  Article  Google Scholar 

  5. 5.

    Humphries KH, Izadnegahdar M, Sedlak T, Saw J, Johnston N, Schenck-Gustafsson K, et al. Sex differences in cardiovascular disease - impact on care and outcomes. Front Neuroendocrinol. 2017;46:46–70.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  6. 6.

    Smilowitz NR, Mahajan AM, Roe MT, Hellkamp AS, Chiswell 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;10(12):e003443.

    PubMed  Article  PubMed Central  Google Scholar 

  7. 7.

    •• Safdar B, Spatz ES, 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. J Am Heart Assoc. 2018;7(13) Findings from this study suggest women present with similar rates of chest pain compared to men. Patients with MINOCA had outcomes comparable to those with obstructive AMI.

  8. 8.

    Lichtman JH, Leifheit EC, Safdar B, Bao H, Krumholz HM, Lorenze NP, et al. Sex differences in the presentation and perception of symptoms among young patients with myocardial infarction: evidence from the VIRGO study (variation in recovery: role of gender on outcomes of young AMI patients). Circulation. 2018;137(8):781–90.

    PubMed  PubMed Central  Article  Google Scholar 

  9. 9.

    Araújo C, Laszczyńska O, Viana M, Melão F, Henriques A, Borges A, et al. Sex differences in presenting symptoms of acute coronary syndrome: the EPIHeart cohort study. BMJ Open. 2018;8(2):e018798.

    PubMed  PubMed Central  Article  Google Scholar 

  10. 10.

    Akhter N, Milford-Beland S, Roe MT, Piana RN, Kao J, Shroff A. Gender differences among patients with acute coronary syndromes undergoing percutaneous coronary intervention in the American College of Cardiology-National Cardiovascular Data Registry (ACC-NCDR). Am Heart J. 2009;157(1):141–8.

    PubMed  Article  PubMed Central  Google Scholar 

  11. 11.

    Ricci B, Cenko E, Vasiljevic Z, Stankovic G, Kedev S, Kalpak O, et al. Acute coronary syndrome: the risk to young women. J Am Heart Assoc. 2017;6(12).

  12. 12.

    Khera S, Kolte D, Gupta T, Subramanian KS, Khanna N, Aronow WS, et al. Temporal trends and sex differences in revascularization and outcomes of ST-segment elevation myocardial infarction in younger adults in the United States. J Am Coll Cardiol. 2015;66(18):1961–72.

    PubMed  Article  PubMed Central  Google Scholar 

  13. 13.

    Worrall-Carter L, McEvedy S, Wilson A, Rahman MA. Gender differences in presentation, coronary intervention, and outcomes of 28,985 acute coronary syndrome patients in Victoria. Australia Womens Health Issues. 2016;26(1):14–20.

    PubMed  Article  PubMed Central  Google Scholar 

  14. 14.

    Bucholz EM, Strait KM, Dreyer RP, Lindau ST, D'Onofrio G, Geda M, et al. Editor’s choice-sex differences in young patients with acute myocardial infarction: a VIRGO study analysis. Eur Heart J Acute Cardiovasc Care. 2017;6(7):610–22.

    PubMed  Article  PubMed Central  Google Scholar 

  15. 15.

    Haukilahti MAE, Holmström L, Vähätalo J, Kenttä T, Tikkanen J, Pakanen L, et al. Sudden cardiac death in women. Circulation. 2019;139(8):1012–21.

    PubMed  Article  PubMed Central  Google Scholar 

  16. 16.

    HISS RG, AVERILL KH, LAMB LE. Electrocardiographic findings in 67,375 asymptomatic subjects. III ventricular rhythms. Am J Cardiol. 1960;6:96–107.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  17. 17.

    Kaid KA, Maqsood A, Cohen M, Rothfeld E. Further characterization of the “persistent juvenile T-wave pattern” in adults. J Electrocardiol. 2008;41(6):644–5.

    Article  Google Scholar 

  18. 18.

    SUAREZ RM. The T-wave of the precordial electrocardiogram at different age levels. Am Heart J. 1946;32(4):480–93.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  19. 19.

    Malhotra A, Dhutia H, Gati S, Yeo TJ, Dores H, Bastiaenen R, et al. Anterior T-wave inversion in young white athletes and nonathletes: prevalence and significance. J Am Coll Cardiol. 2017;69(1):1–9.

    PubMed  Article  PubMed Central  Google Scholar 

  20. 20.

    Aro AL, Anttonen O, Tikkanen JT, Junttila MJ, Kerola T, Rissanen HA, et al. Prevalence and prognostic significance of T-wave inversions in right precordial leads of a 12-lead electrocardiogram in the middle-aged subjects. Circulation. 2012;125(21):2572–7.

    PubMed  Article  PubMed Central  Google Scholar 

  21. 21.

    Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth universal definition of myocardial infarction (2018). Circulation. 2018;138(20):e618–e51.

    PubMed  Article  PubMed Central  Google Scholar 

  22. 22.

    Carlton EW, Cullen L, Than M, Gamble J, Khattab A, Greaves K. A novel diagnostic protocol to identify patients suitable for discharge after a single high-sensitivity troponin. Heart. 2015;101(13):1041–6.

    PubMed  PubMed Central  Article  Google Scholar 

  23. 23.

    Weber M, Bazzino O, Navarro Estrada JL, de Miguel R, Salzberg S, Fuselli JJ, et al. Improved diagnostic and prognostic performance of a new high-sensitive troponin T assay in patients with acute coronary syndrome. Am Heart J. 2011;162(1):81–8.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  24. 24.

    Reichlin T, Hochholzer W, Bassetti S, Steuer S, Stelzig C, Hartwiger S, et al. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med. 2009;361(9):858–67.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  25. 25.

    Giannitsis E, Kurz K, Hallermayer K, Jarausch J, Jaffe AS, Katus HA. Analytical validation of a high-sensitivity cardiac troponin T assay. Clin Chem. 2010;56(2):254–61.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  26. 26.

    Apple FS, Simpson PA, Murakami MM. Defining the serum 99th percentile in a normal reference population measured by a high-sensitivity cardiac troponin I assay. Clin Biochem. 2010;43(12):1034–6.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  27. 27.

    Sherwood MW, Kristin NL. High-sensitivity troponin assays: evidence, indications, and reasonable use. J Am Heart Assoc. 2014;3(1):e000403.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  28. 28.

    Kimenai DM, Janssen EBNJ, Eggers KM, Lindahl B, den Ruijter HM, Bekers O, et al. Sex-specific versus overall clinical decision limits for cardiac troponin I and T for the diagnosis of acute myocardial infarction: a systematic review. Clin Chem. 2018;64(7):1034–43.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  29. 29.

    Shah ASV, Anand A, Strachan FE, Ferry AV, Lee KK, Chapman AR, et al. High-sensitivity troponin in the evaluation of patients with suspected acute coronary syndrome: a stepped-wedge, cluster-randomised controlled trial. Lancet. 2018;392(10151):919–28.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  30. 30.

    Shah AS, Griffiths M, Lee KK, McAllister DA, Hunter AL, Ferry AV, et al. High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study. BMJ. 2015;350:g7873.

    PubMed  PubMed Central  Article  Google Scholar 

  31. 31.

    Tan LZH, Chow K, Loh J, Chua T, Tan H, Foo D, et al. Door-to-balloon time correlates better with patients outcomes than symptom-to-balloon time. J Am Coll Cardiol. 2016;67(13).

  32. 32.

    Scalise RFM, Salito AM, Polimeni A, Garcia-Ruiz V, Virga V, Frigione P, et al. Radial artery access for percutaneous cardiovascular interventions: contemporary insights and novel approaches. J Clin Med. 2019;8(10).

  33. 33.

    Liu J, Elbadawi A, Elgendy IY, et al. Age-stratified sex disparities in care and outcomes in patients with ST-elevation myocardial infarction. Am J Med. 2020;S0002-9343(20)30375-2. https://doi.org/10.1016/j.amjmed.2020.03.059

  34. 34.

    Wilkinson C, Bebb O, Dondo TB, Munyombwe T, Casadei B, Clarke S, et al. Sex differences in quality indicator attainment for myocardial infarction: a nationwide cohort study. Heart. 2019;105(7):516–23.

    PubMed  Article  PubMed Central  Google Scholar 

  35. 35.

    Hao Y, Liu J, Yang N, Smith SC, Huo Y, Fonarow GC, et al. Sex differences in in-hospital management and outcomes of patients with acute coronary syndrome. Circulation. 2019;139(15):1776–85.

    PubMed  Article  Google Scholar 

  36. 36.

    Dai J, Xing L, Jia H, Zhu Y, Zhang S, Hu S, et al. In vivo predictors of plaque erosion in patients with ST-segment elevation myocardial infarction: a clinical, angiographical, and intravascular optical coherence tomography study. Eur Heart J. 2018;39(22):2077–85.

    PubMed  Article  Google Scholar 

  37. 37.

    Yamamoto E, Yonetsu T, Kakuta T, Soeda T, Saito Y, Yan BP, et al. Clinical and laboratory predictors for plaque erosion in patients with acute coronary syndromes. J Am Heart Assoc. 2019;8(21):e012322.

    PubMed  PubMed Central  Article  Google Scholar 

  38. 38.

    Jia H, Abtahian F, Aguirre AD, Lee S, Chia S, Lowe H, et al. In vivo diagnosis of plaque erosion and calcified nodule in patients with acute coronary syndrome by intravascular optical coherence tomography. J Am Coll Cardiol. 2013;62(19):1748–58.

    PubMed  Article  Google Scholar 

  39. 39.

    Farb A, Burke AP, Tang AL, Liang TY, Mannan P, Smialek J, et al. Coronary plaque erosion without rupture into a lipid core. A frequent cause of coronary thrombosis in sudden coronary death. Circulation. 1996;93(7):1354–63.

    CAS  PubMed  Article  Google Scholar 

  40. 40.

    Pepine CJ, Ferdinand KC, Shaw LJ, Light-McGroary KA, Shah RU, Gulati M, et al. Emergence of nonobstructive coronary artery disease: a woman's problem and need for change in definition on angiography. J Am Coll Cardiol. 2015;66(17):1918–33.

    PubMed  PubMed Central  Article  Google Scholar 

  41. 41.

    Agewall S, Beltrame JF, Reynolds HR, Niessner A, Rosano G, Caforio AL, et al. ESC working group position paper on myocardial infarction with non-obstructive coronary arteries. Eur Heart J. 2017;38(3):143–53.

    PubMed  PubMed Central  Google Scholar 

  42. 42.

    • Tamis-Holland JE, Jneid H, Reynolds HR, Agewall S, Brilakis ES, Brown TM, et al. Contemporary diagnosis and management of patients with myocardial Infarction in the absence of obstructive coronary artery disease: a scientific statement from the American Heart Association. Circulation. 2019;139(18):e891–908 Provides a thorough and comprehensive review outlining the different causes of MINOCA.

    PubMed  Article  PubMed Central  Google Scholar 

  43. 43.

    Vidal-Perez R, Abou Jokh Casas C, Agra-Bermejo RM, Alvarez-Alvarez B, Grapsa J, Fontes-Carvalho R, et al. Myocardial infarction with non-obstructive coronary arteries: a comprehensive review and future research directions. World J Cardiol. 2019;11(12):305–15.

    PubMed  PubMed Central  Article  Google Scholar 

  44. 44.

    Roswell RO, Kunkes J, Chen AY, Chiswell K, Iqbal S, Roe MT, et al. Impact of sex and contact-to-device time on clinical outcomes in acute ST-segment elevation myocardial infarction-findings from the National Cardiovascular Data Registry. J Am Heart Assoc. 2017;6(1).

  45. 45.

    Grady D, Herrington D, Bittner V, Blumenthal R, Davidson M, Hlatky M, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: heart and estrogen/progestin replacement study follow-up (HERS II). JAMA. 2002;288(1):49–57.

    PubMed  Article  PubMed Central  Google Scholar 

  46. 46.

    Bertrand ME, LaBlanche JM, Tilmant PY, Thieuleux FA, Delforge MR, Carre AG, et al. Frequency of provoked coronary arterial spasm in 1089 consecutive patients undergoing coronary arteriography. Circulation. 1982;65(7):1299–306.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  47. 47.

    Aziz A, Hansen HS, Sechtem U, Prescott E, Ong P. Sex-related differences in vasomotor function in patients with angina and unobstructed coronary arteries. J Am Coll Cardiol. 2017;70(19):2349–58.

    PubMed  Article  PubMed Central  Google Scholar 

  48. 48.

    Sueda S, Kohno H, Fukuda H, Ochi N, Kawada H, Hayashi Y, et al. Frequency of provoked coronary spasms in patients undergoing coronary arteriography using a spasm provocation test via intracoronary administration of ergonovine. Angiology. 2004;55(4):403–11.

    PubMed  Article  PubMed Central  Google Scholar 

  49. 49.

    Lee DH, Park TK, Seong CS, Gwag HB, Lim AY, Oh MS, et al. Gender differences in long-term clinical outcomes and prognostic factors in patients with vasospastic angina. Int J Cardiol. 2017;249:6–11.

    PubMed  Article  PubMed Central  Google Scholar 

  50. 50.

    Yoshida K, Utsunomiya T, Morooka T, Yazawa M, Kido K, Ogawa T, et al. Mental stress test is an effective inducer of vasospastic angina pectoris: comparison with cold pressor, hyperventilation and master two-step exercise test. Int J Cardiol. 1999;70(2):155–63.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  51. 51.

    Waters DD, Szlachcic J, Bonan R, Miller DD, Dauwe F, Theroux P. Comparative sensitivity of exercise, cold pressor and ergonovine testing in provoking attacks of variant angina in patients with active disease. Circulation. 1983;67(2):310–5.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  52. 52.

    Mittleman MA, Mintzer D, Maclure M, Tofler GH, Sherwood JB, Muller JE. Triggering of myocardial infarction by cocaine. Circulation. 1999;99(21):2737–41.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  53. 53.

    Kevil CG, Goeders NE, Woolard MD, Bhuiyan MS, Dominic P, Kolluru GK, et al. Methamphetamine use and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2019;39(9):1739–46.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  54. 54.

    Beltrame JF, Crea F, Kaski JC, Ogawa H, Ong P, Sechtem U, et al. International standardization of diagnostic criteria for vasospastic angina. Eur Heart J. 2017;38(33):2565–8.

    PubMed  PubMed Central  Google Scholar 

  55. 55.

    Amsterdam EA, Wenger NK, Brindis RG, Casey DE, Ganiats TG, Holmes DR, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. Circulation. 2014;130(25):e344–426.

    PubMed  PubMed Central  Google Scholar 

  56. 56.

    Montone RA, Niccoli G, Fracassi F, Russo M, Gurgoglione F, Cammà G, et al. Patients with acute myocardial infarction and non-obstructive coronary arteries: safety and prognostic relevance of invasive coronary provocative tests. Eur Heart J. 2018;39(2):91–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. 57.

    Takagi Y, Yasuda S, Tsunoda R, Ogata Y, Seki A, Sumiyoshi T, et al. Clinical characteristics and long-term prognosis of vasospastic angina patients who survived out-of-hospital cardiac arrest: multicenter registry study of the Japanese Coronary Spasm Association. Circ Arrhythm Electrophysiol. 2011;4(3):295–302.

    PubMed  Article  PubMed Central  Google Scholar 

  58. 58.

    Bory M, Pierron F, Panagides D, Bonnet JL, Yvorra S, Desfossez L. Coronary artery spasm in patients with normal or near normal coronary arteries. Long-term follow-up of 277 patients. Eur Heart J. 1996;17(7):1015–21.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  59. 59.

    Slavich M, Patel RS. Coronary artery spasm: current knowledge and residual uncertainties. Int J Cardiol Heart Vasc. 2016;10:47–53.

    PubMed  PubMed Central  Google Scholar 

  60. 60.

    Ahn JM, Lee KH, Yoo SY, Cho YR, Suh J, Shin ES, et al. Prognosis of variant angina manifesting as aborted sudden cardiac death. J Am Coll Cardiol. 2016;68(2):137–45.

    PubMed  Article  PubMed Central  Google Scholar 

  61. 61.

    Saw J, Mancini GBJ, Humphries KH. Contemporary review on spontaneous coronary artery dissection. J Am Coll Cardiol. 2016;68(3):297–312.

    PubMed  Article  PubMed Central  Google Scholar 

  62. 62.

    Saw J, Humphries K, Aymong E, Sedlak T, Prakash R, Starovoytov A, et al. Spontaneous coronary artery dissection: clinical outcomes and risk of recurrence. J Am Coll Cardiol. 2017;70(9):1148–58.

    PubMed  Article  PubMed Central  Google Scholar 

  63. 63.

    Nishiguchi T, Tanaka A, Ozaki Y, Taruya A, Fukuda S, Taguchi H, et al. Prevalence of spontaneous coronary artery dissection in patients with acute coronary syndrome. Eur Heart J Acute Cardiovasc Care. 2016;5(3):263–70.

    PubMed  Article  PubMed Central  Google Scholar 

  64. 64.

    Krittanawong C, Kumar A, Virk HUH, Yue B, Wang Z, Bhatt DL. Trends in incidence, characteristics, and in-hospital outcomes of patients presenting with spontaneous coronary artery dissection (from a National Population-Based Cohort Study between 2004 and 2015). Am J Cardiol. 2018;122(10):1617–23.

    PubMed  Article  PubMed Central  Google Scholar 

  65. 65.

    Mahmoud AN, Taduru SS, Mentias A, Mahtta D, Barakat AF, Saad M, et al. Trends of incidence, clinical presentation, and in-hospital mortality among women with acute myocardial infarction with or without spontaneous coronary artery dissection: a population-based analysis. JACC Cardiovasc Intervent. 2018;11(1):80–90.

    Article  Google Scholar 

  66. 66.

    Basso C, Morgagni GL, Thiene G. Spontaneous coronary artery dissection: a neglected cause of acute myocardial ischaemia and sudden death. Heart. 1996;75(5):451–4.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  67. 67.

    Michelis KC, Olin JW, Kadian-Dodov D, d'Escamard V, Kovacic JC. Coronary artery manifestations of fibromuscular dysplasia. J Am Coll Cardiol. 2014;64(10):1033–46.

    PubMed  PubMed Central  Article  Google Scholar 

  68. 68.

    Lobo AS, Cantu SM, Sharkey SW, Grey EZ, Storey K, Witt D, et al. Revascularization in patients with spontaneous coronary artery dissection and ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2019;74(10):1290–300.

    PubMed  Article  PubMed Central  Google Scholar 

  69. 69.

    Hayes SN, Kim ESH, Saw J, Adlam D, Arslanian-Engoren C, Economy KE, et al. Spontaneous coronary artery dissection: current state of the science: a scientific statement from the American Heart Association. Circulation. 2018;137(19):e523–e57.

    PubMed  PubMed Central  Article  Google Scholar 

  70. 70.

    Ghadri JR, Sarcon A, Diekmann J, Bataiosu DR, Cammann VL, Jurisic S, et al. Happy heart syndrome: role of positive emotional stress in takotsubo syndrome. Eur Heart J. 2016;37(37):2823–9.

    PubMed  PubMed Central  Article  Google Scholar 

  71. 71.

    Sharkey SW, Lesser JR, Maron MS, Maron BJ. Why not just call it tako-tsubo cardiomyopathy: a discussion of nomenclature. J Am Coll Cardiol. 2011;57(13):1496–7.

    PubMed  Article  PubMed Central  Google Scholar 

  72. 72.

    Ghadri JR, Wittstein IS, Prasad A, Sharkey S, Dote K, Akashi YJ, et al. International expert consensus document on Takotsubo syndrome (part I): clinical characteristics, diagnostic criteria, and pathophysiology. Eur Heart J. 2018;39(22):2032–46.

    PubMed  PubMed Central  Article  Google Scholar 

  73. 73.

    Ghadri JR, Ruschitzka F, Luscher TF, Templin C. Takotsubo cardiomyopathy: still much more to learn. Heart. 2014;100(22):1804–12.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  74. 74.

    Raab W, Stark E, Macmillan WH, Gigee WR. Sympathogenic origin and antiadrenergic prevention of stress-induced myocardial lesions. Am J Cardiol. 1961;8:203–11.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  75. 75.

    Naegele M, Flammer AJ, Enseleit F, Roas S, Frank M, Hirt A, et al. Endothelial function and sympathetic nervous system activity in patients with Takotsubo syndrome. Int J Cardiol. 2016;224:226–30.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  76. 76.

    Pelliccia F, Kaski JC, Crea F, Camici PG. Pathophysiology of Takotsubo syndrome. Circulation. 2017;135(24):2426–41.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  77. 77.

    Dote K, Sato H, Tateishi H, Uchida T, Ishihara M. Myocardial stunning due to simultaneous multivessel coronary spasms: a review of 5 cases. J Cardiol. 1991;21(2):203–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78.

    Scantlebury DC, Prasad A, Rabinstein AA, Best PJ. Prevalence of migraine and Raynaud phenomenon in women with apical ballooning syndrome (Takotsubo or stress cardiomyopathy). Am J Cardiol. 2013;111(9):1284–8.

    PubMed  Article  PubMed Central  Google Scholar 

  79. 79.

    Tsuchihashi K, Ueshima K, Uchida T, Oh-mura N, Kimura K, Owa M, et al. Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. Angina pectoris-myocardial infarction investigations in Japan. J Am Coll Cardiol. 2001;38(1):11–8.

    CAS  PubMed  Article  Google Scholar 

  80. 80.

    Camici PG, Crea F. Microvascular angina: a women’s affair? Circ Cardiovasc Imaging. 2015;8(4).

  81. 81.

    Kaski JC. Cardiac syndrome X in women: the role of oestrogen deficiency. Heart. 2006;92 Suppl 3:iii5–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Vitale C, Mendelsohn ME, Rosano GM. Gender differences in the cardiovascular effect of sex hormones. Nat Rev Cardiol. 2009;6(8):532–42.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  83. 83.

    Prasad A, Lerman A, Rihal CS. Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction. Am Heart J. 2008;155(3):408–17.

    PubMed  Article  PubMed Central  Google Scholar 

  84. 84.

    Prasad A, Dangas G, Srinivasan M, Yu J, Gersh BJ, Mehran R, et al. Incidence and angiographic characteristics of patients with apical ballooning syndrome (takotsubo/stress cardiomyopathy) in the HORIZONS-AMI trial: an analysis from a multicenter, international study of ST-elevation myocardial infarction. Catheter Cardiovasc Interv. 2014;83(3):343–8.

    PubMed  Article  PubMed Central  Google Scholar 

  85. 85.

    Sy F, Basraon J, Zheng H, Singh M, Richina J, Ambrose JA. Frequency of Takotsubo cardiomyopathy in postmenopausal women presenting with an acute coronary syndrome. Am J Cardiol. 2013;112(4):479–82.

    PubMed  Article  PubMed Central  Google Scholar 

  86. 86.

    Wedekind H, Moller K, Scholz KH. Tako-tsubo cardiomyopathy. Incidence in patients with acute coronary syndrome. Herz. 2006;31(4):339–46.

    PubMed  Article  PubMed Central  Google Scholar 

  87. 87.

    Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu DR, Jaguszewski M, et al. Clinical features and outcomes of Takotsubo (stress) cardiomyopathy. N Engl J Med. 2015;373(10):929–38.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  88. 88.

    Farkowski MM, Pytkowski M, Maciag A, Golicki D, Wood KA, Kowalik I, et al. Gender-related differences in outcomes and resource utilization in patients undergoing radiofrequency ablation of supraventricular tachycardia: results from patients’ perspective on radiofrequency catheter ablation of AVRT and AVNRT study. Europace. 2014;16(12):1821–7.

    PubMed  Article  PubMed Central  Google Scholar 

  89. 89.

    Nguyen TH, Neil CJ, Sverdlov AL, Mahadavan G, Chirkov YY, Kucia AM, et al. N-terminal pro-brain natriuretic protein levels in takotsubo cardiomyopathy. Am J Cardiol. 2011;108(9):1316–21.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  90. 90.

    Yoshikawa T. Takotsubo cardiomyopathy, a new concept of cardiomyopathy: clinical features and pathophysiology. Int J Cardiol. 2015;182:297–303.

    PubMed  Article  PubMed Central  Google Scholar 

  91. 91.

    Ali M, Rigopoulos AG, Ali K, et al. Advancements in the diagnostic workup, prognostic evaluation, and treatment of takotsubo syndrome. Heart Failure Reviews. 2020;25(5):757–771. https://doi.org/10.1007/s10741-019-09843-9.

  92. 92.

    Ghadri JR, Kato K, Cammann VL, Gili S, Jurisic S, Di Vece D, et al. Long-term prognosis of patients with Takotsubo syndrome. J Am Coll Cardiol. 2018;72(8):874–82.

    PubMed  Article  PubMed Central  Google Scholar 

  93. 93.

    Pelliccia F, Parodi G, Greco C, Antoniucci D, Brenner R, Bossone E, et al. Comorbidities frequency in Takotsubo syndrome: an international collaborative systematic review including 1109 patients. Am J Med. 2015;128(6):654 e11–9.

    Article  Google Scholar 

  94. 94.

    Manginas A, Rigopoulos AG, Bigalke B, Sakellaropoulos S, Ali M, Mavrogeni S, et al. Takotsubo syndrome - adding pieces to a complex puzzle. BMC Cardiovasc Disord. 2017;17(1):296.

    PubMed  PubMed Central  Article  Google Scholar 

  95. 95.

    Tornvall P, Collste O, Ehrenborg E, Jarnbert-Petterson H. A case-control study of risk markers and mortality in Takotsubo stress cardiomyopathy. J Am Coll Cardiol. 2016;67(16):1931–6.

    PubMed  Article  PubMed Central  Google Scholar 

  96. 96.

    Lyon AR, Rees PS, Prasad S, Poole-Wilson PA, Harding SE. Stress (Takotsubo) cardiomyopathy--a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning. Nat Clin Pract Cardiovasc Med. 2008;5(1):22–9.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  97. 97.

    Sharkey SW, Maron BJ. Epidemiology and clinical profile of Takotsubo cardiomyopathy. Circ J. 2014;78(9):2119–28.

    PubMed  Article  PubMed Central  Google Scholar 

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Correspondence to Martha Gulati.

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This article is part of the Topical Collection on Management of Acute Coronary Syndromes

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Trutter, L., Bigeh, A., Pecci, C. et al. Diagnostic and Management Dilemmas in Women Presenting with Acute Coronary Syndromes. Curr Cardiol Rep 22, 163 (2020). https://doi.org/10.1007/s11886-020-01410-1

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Keywords

  • Cardiovascular disease
  • Myocardial infarction
  • Acute coronary syndrome
  • Women
  • Sex differences
  • Myocardial infarction with non-obstructive coronaries (MINOCA)