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Coronary microvascular dysfunction in patients with acute coronary syndrome and no obstructive coronary artery disease

  • Antonio De Vita
  • Laura Manfredonia
  • Priscilla Lamendola
  • Angelo Villano
  • Salvatore Emanuele Ravenna
  • Antonio Bisignani
  • Giampaolo Niccoli
  • Gaetano Antonio LanzaEmail author
  • Filippo Crea
Original Paper
  • 126 Downloads

Abstract

Background

Between 10 and 15% of patients admitted for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) show no obstructive coronary artery disease (NO-CAD) at angiography. Coronary microvascular spasm is a possible mechanism of the syndrome, but there are scarce data about coronary microvascular function in these patients.

Objectives

To assess coronary microvascular function in patients with NSTE-ACS and NO-CAD.

Methods

We studied 30 patients (67 ± 10 years, 19 female) with NSTE-ACS and NO-CAD. Specific causes of NSTE-ACS presentation (e.g., variant angina, takotsubo disease, tachyarrhythmias, etc.) were excluded. Coronary blood flow (CBF) velocity response to IV ergonovine (6 µg/kg up to a maximal dose of 400 µg) was evaluated before discharge by transthoracic Doppler echocardiography. CBF response to IV adenosine (140 μg/kg/min) and cold pressor test (CPT) was also assessed after 1 month. Ten age- and sex-matched patients with non-cardiac chest pain served as controls. Vasoactive tests were repeated after 12 months in 10 NSTE-ACS patients.

Results

The ergonovine/basal CBF velocity ratio was 0.79 ± 0.09 and 0.99 ± 0.01 in patients and controls, respectively (p < 0.001). The adenosine/basal CBF velocity ratio was 1.46 ± 0.2 and 3.25 ± 1.2 in patients and controls, respectively (p < 0.001), and the CPT/basal CBF velocity ratio was 1.36 ± 0.2 and 2.43 ± 0.3 in the 2 groups, respectively (p < 0.001). In 10 patients assessed after 12 months, CBF velocity responses to ergonovine, adenosine, and CPT were found to be unchanged.

Conclusions

Patients with NSTE-ACS and NO-CAD exhibit a significant coronary dysfunction, which seems to involve both an increased constrictor reactivity, likely mainly involving coronary microcirculation, and a reduced microvascular dilator function, both persisting at 12-month follow-up.

Keywords

Coronary microvascular dysfunction Acute coronary syndrome with no obstructive coronary artery disease Microvascular spasm 

Notes

Funding

None.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Pasupathy S, Air T, Dreyer RP, Tavella R, Beltrame JF (2015) Systematic review of patients presenting with suspected myocardial infarction and nonobstructive coronary arteries. Circulation 131:861–870CrossRefGoogle Scholar
  2. 2.
    Gehrie ER, Reynolds HR, Chen AY et al (2009) Characterization and outcomes of women and men with non-ST-segment elevation myocardial infarction and nonobstructive coronary artery disease: results from the can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines (CRUSADE) quality improvement initiative. Am Heart J 158:688–694CrossRefGoogle Scholar
  3. 3.
    Patel MR, Chen AY, Peterson ED et al (2006) Prevalence, predictors, and outcomes of patients with non-ST-segment elevation myocardial infarction and insignificant coronary artery disease: results from the can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines (CRUSADE) initiative. Am Heart J 152:641–647CrossRefGoogle Scholar
  4. 4.
    Bugiardini R, Manfrini O, De Ferrari GM (2006) Unanswered questions for management of acute coronary syndrome: risk stratification of patients with minimal disease or normal findings on coronary angiography. Arch Intern Med 166:1391–1395CrossRefGoogle Scholar
  5. 5.
    Hochman JS, Tamis JE, Thompson TD et al (1999) Sex, clinical presentation, and outcome in patients with acute coronary syndromes. Global use of strategies to open occluded coronary arteries in acute coronary syndromes IIb investigators. N Engl J Med 341:226–232CrossRefGoogle Scholar
  6. 6.
    Planer D, Mehran R, Ohman EM et al (2014) Prognosis of patients with non-ST-segment-elevation myocardial infarction and nonobstructive coronary artery disease: propensity-matched analysis from the acute catheterization and urgent intervention triage strategy trial. Circ Cardiovasc Interv 7:285–293CrossRefGoogle Scholar
  7. 7.
    Lanza GA, Careri G, Stazi A, Villano A, De Vita A, Aurigemma C, Crea F (2016) Clinical spectrum and outcome of patients with non-ST-segment elevation acute coronary syndrome and no obstructive coronary atherosclerosis. Circ J 80:1600–1606CrossRefGoogle Scholar
  8. 8.
    Mohri M, Koyanagi M, Egashira K, Tagawa H, Ichiki T, Shimokawa H, Takeshita A (1998) Angina pectoris caused by coronary microvascular spasm. Lancet 351:1165–1169CrossRefGoogle Scholar
  9. 9.
    Lanza GA, Crea F (2014) Acute coronary syndromes without obstructive coronary atherosclerosis: the tiles of a complex puzzle. Circ Cardiovasc Interv 7:278–281CrossRefGoogle Scholar
  10. 10.
    Beltrame JF, Limaye SB, Wuttke RD, Horowitz JD (2003) Coronary hemodynamic and metabolic studies of the coronary slow flow phenomenon. Am Heart J 146:84–90CrossRefGoogle Scholar
  11. 11.
    Montone RA, Niccoli G, Fracassi F et al (2018) Patients with acute myocardial infarction and non-obstructive coronary arteries: safety and prognostic relevance of invasive coronary provocative tests. Eur Heart J 39:91–98Google Scholar
  12. 12.
    Motz W, Vogt M, Rabenau O, Scheler S, Lückhoff A, Strauer BE (1991) Evidence of endothelial dysfunction in coronary resistance vessels in patients with angina pectoris and normal coronary angiograms. Am J Cardiol 68:996–1003CrossRefGoogle Scholar
  13. 13.
    Chauhan A, Mullins PA, Taylor G, Petch MC, Schofield PM (1993) Effect of hyperventilation and mental stress on coronary blood flow in syndrome X. Br Heart J 69:516–524CrossRefGoogle Scholar
  14. 14.
    Ong P, Athanasiadis A, Borgulya G et al (2014) Clinical usefulness, angiographic characteristics, and safety evaluation of intracoronary acetylcholine provocation testing among 921 consecutive white patients with unobstructed coronary arteries. Circulation 129:1723–1730CrossRefGoogle Scholar
  15. 15.
    Ong P, Athanasiadis A, Mahrholdt H, Borgulya G, Sechtem U, Kaski JC (2012) Increased coronary vasoconstrictor response to acetylcholine in women with chest pain and normal coronary arteriograms (cardiac syndrome X). Clin Res Cardiol 101:673–681CrossRefGoogle Scholar
  16. 16.
    Lanza GA (2016) Angina Pectoris and myocardial ischemia in the absence of obstructive coronary artery disease: role of diagnostic tests. Curr Cardiol Rep 18:15CrossRefGoogle Scholar
  17. 17.
    Bertrand ME, LaBlanche JM, Tilmant PY et al (1982) Frequency of provoked coronary arterial spasm in 1089 consecutive patients undergoing coronary arteriography. Circulation 65:1299–1306CrossRefGoogle Scholar
  18. 18.
    Heupler FA Jr, Proudfit WL, Razavi M, Shirey EK, Greenstreet R, Sheldon WC (1978) Ergonovine maleate provocative test for coronary arterial spasm. Am J Cardiol 41:631–640CrossRefGoogle Scholar
  19. 19.
    Reichlin T, Irfan A, Twerenbold R, Reiter M, Hochholzer W, Burkhalter H et al (2011) Utility of absolute and relative changes in cardiac troponin concentrations in the early diagnosis of acute myocardial infarction. Circulation 124:136–145CrossRefGoogle Scholar
  20. 20.
    Sestito A, Lanza GA, Di Monaco A, Lamendola P, Careri G, Tarzia P, Pinnacchio G, Battipaglia I, Crea F (2011) Relation between cardiovascular risk factors and coronary microvascular dysfunction in cardiac syndrome X. J Cardiovasc Med 12:322–327CrossRefGoogle Scholar
  21. 21.
    Lanza GA, Buffon A, Sestito A, Natale L, Sgueglia GA, Galiuto L, Infusino F, Mariani L, Centola A, Crea F (2008) Relation between stressinduced myocardial perfusion defects on cardiovascular magnetic resonance and coronary microvascular dysfunction in patients with cardiac syndrome X. J Am Coll Cardiol 51:466–472CrossRefGoogle Scholar
  22. 22.
    Agewall S, Giannitsis E, Jernberg T, Katus H (2011) Troponin elevation in coronary vs. non-coronary disease. Eur Heart J 32:404–411CrossRefGoogle Scholar
  23. 23.
    Thygesen K, Alpert JS, Jaffe AS et al (2018) Fourth universal definition of myocardial infarction. Circulation 138:e618–e651CrossRefGoogle Scholar
  24. 24.
    Ong P, Athanasiadis A, Hill S, Vogelsberg H, Voehringer M, Sechtem U (2008) Coronary artery spasm as a frequent cause of acute coronary syndrome: the CASPAR (Coronary Artery Spasm in Patients With Acute Coronary Syndrome) Study. J Am Coll Cardiol 52:523–527CrossRefGoogle Scholar
  25. 25.
    Legrand V, Deliege M, Henrard L, Boland J, Kulbertus H (1982) Patients with myocardial infarction and normal coronary arteriogram. Chest 82:678–685CrossRefGoogle Scholar
  26. 26.
    Pecora MJ, Roubin GS, Cobbs BW Jr, Ellis SG, Weintraub WS, King SB 3rd (1988) Presentation and late outcome of myocardial infarction in the absence of angiographically significant coronary artery disease. Am J Cardiol 62:363–367CrossRefGoogle Scholar
  27. 27.
    Sun H, Mohri M, Shimokawa H, Usui M, Urakami L, Takeshita A (2002) Coronary microvascular spasm causes myocardial ischemia in patients with vasospastic angina. J Am Coll Cardiol 39:847–851CrossRefGoogle Scholar
  28. 28.
    Beltrame JF, Crea F, Kaski JC, Ogawa H, Ong P, Sechtem U, Shimokawa H, Bairey Merz CN, Coronary Vasomotion Disorders International Study Group (COVADIS) (2017) International standardization of diagnostic criteria for vasospastic angina. Eur Heart J 38:2565–2568Google Scholar
  29. 29.
    Völz S, Svedlund S, Andersson B, Li-Ming G, Rundqvist B (2017) Coronary flow reserve in patients with resistant hypertension. Clin Res Cardiol 106:151–157CrossRefGoogle Scholar
  30. 30.
    Bugiardini R, Pozzati A, Ottani F, Morgagni GL, Puddu P (1993) Vasotonic angina: a spectrum of ischemic syndromes involving functional abnormalities of the epicardial and microvascular coronary circulation. J Am Coll Cardiol 22:417–425CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Antonio De Vita
    • 1
  • Laura Manfredonia
    • 1
  • Priscilla Lamendola
    • 1
  • Angelo Villano
    • 1
  • Salvatore Emanuele Ravenna
    • 1
  • Antonio Bisignani
    • 1
  • Giampaolo Niccoli
    • 1
  • Gaetano Antonio Lanza
    • 1
    Email author
  • Filippo Crea
    • 1
  1. 1.Department of Cardiovascular DiseaseFondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Istituto di CardiologiaRomeItaly

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