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Erschienen in: Clinical Research in Cardiology 4/2020

03.07.2019 | Original Paper

Clinical, angiographic and echocardiographic correlates of epicardial and microvascular spasm in patients with myocardial ischaemia and non-obstructive coronary arteries

verfasst von: Rocco Antonio Montone, Giampaolo Niccoli, Michele Russo, Marta Giaccari, Marco Giuseppe Del Buono, Maria Chiara Meucci, Filippo Gurgoglione, Rocco Vergallo, Domenico D’Amario, Antonino Buffon, Antonio M. Leone, Francesco Burzotta, Cristina Aurigemma, Carlo Trani, Giovanna Liuzzo, Gaetano A. Lanza, Filippo Crea

Erschienen in: Clinical Research in Cardiology | Ausgabe 4/2020

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Abstract

Background

Coronary vasomotor dysfunction represents an important mechanism responsible for myocardial ischaemia in patients with non-obstructive coronary artery disease (CAD). The use of invasive provocative tests allows identifying patients with epicardial or microvascular spasm. Of note, clinical characteristics associated with the occurrence of epicardial or microvascular spasm have still not completely clarified.

Methods and results

We prospectively enrolled consecutive patients undergoing coronary angiography for suspected myocardial ischaemia/necrosis with evidence of non-obstructive CAD and undergoing intracoronary provocative test for suspected vasomotor dysfunction. Patients with a positive provocative test were enrolled. Clinical, echocardiographic and angiographic characteristics of patients were evaluated according to the pattern of vasomotor dysfunction (epicardial vs. microvascular spasm). We included 120 patients [68 patients with stable angina and 52 patients with myocardial infarction and non-obstructive coronary arteries (MINOCA)]. In particular, 77 (64.2%) patients had a provocative test positive for epicardial spasm and 43 (35.8%) patients for microvascular spasm. Patients with epicardial spasm were more frequently males, smokers, had higher rates of diffuse coronary atherosclerosis at angiography and more frequently presented with MINOCA. On the other hand, patients with microvascular spasm presented more frequently diastolic dysfunction. At multivariate logistic regression analysis male sex, smoking, and diffuse coronary atherosclerosis were independent predictors for the occurrence of epicardial spasm.

Conclusions

Our study showed that specific clinical features are associated with different responses to intracoronary provocative test. Epicardial spasm is more frequent in males and in MINOCA patients, whereas microvascular spasm is more frequent in patients with stable angina and is associated with diastolic dysfunction.
Literatur
1.
Zurück zum Zitat Timmis A, Townsend N, Gale C, Grobbee R, Maniadakis N, Flather M, Wilkins E, Wright L, Vos R, Bax J, Blum M, Pinto F, Vardas P (2018) Atlas writing group—European society of cardiology: cardiovascular disease statistics 2017. Eur Heart J 39:508–579PubMedCrossRef Timmis A, Townsend N, Gale C, Grobbee R, Maniadakis N, Flather M, Wilkins E, Wright L, Vos R, Bax J, Blum M, Pinto F, Vardas P (2018) Atlas writing group—European society of cardiology: cardiovascular disease statistics 2017. Eur Heart J 39:508–579PubMedCrossRef
2.
Zurück zum Zitat Bugiardini R, Merz CN (2005) Angina with “normal” coronary arteries: a changing philosophy. JAMA 293:477–484PubMedCrossRef Bugiardini R, Merz CN (2005) Angina with “normal” coronary arteries: a changing philosophy. JAMA 293:477–484PubMedCrossRef
3.
Zurück zum Zitat Crea F, Camici PG, Merz CN (2014) Coronary microvascular dysfunction: an update. Eur Heart J 35:1101–1111PubMedCrossRef Crea F, Camici PG, Merz CN (2014) Coronary microvascular dysfunction: an update. Eur Heart J 35:1101–1111PubMedCrossRef
4.
Zurück zum Zitat Lanza GA, Crea F (2010) Primary coronary microvascular dysfunction: clinical presentation, pathophysiology, and management. Circulation 121:2317–2325PubMedCrossRef Lanza GA, Crea F (2010) Primary coronary microvascular dysfunction: clinical presentation, pathophysiology, and management. Circulation 121:2317–2325PubMedCrossRef
5.
Zurück zum Zitat Lanza GA, Careri G, Crea F (2011) Mechanisms of coronary artery spasm. Circulation 124:1774–1782PubMedCrossRef Lanza GA, Careri G, Crea F (2011) Mechanisms of coronary artery spasm. Circulation 124:1774–1782PubMedCrossRef
6.
Zurück zum Zitat Kaski JC, Crea F, Gersh BJ, Camici PG (2018) Reappraisal of ischemic heart disease. Circulation 138:1463–1480PubMedCrossRef Kaski JC, Crea F, Gersh BJ, Camici PG (2018) Reappraisal of ischemic heart disease. Circulation 138:1463–1480PubMedCrossRef
8.
Zurück zum Zitat Yu M, Zhang Q, Huang X (2018) Acute coronary syndrome due to right coronary spasm and documented lambda-like J waves. Clin Res Cardiol 107:729–732PubMedCrossRef Yu M, Zhang Q, Huang X (2018) Acute coronary syndrome due to right coronary spasm and documented lambda-like J waves. Clin Res Cardiol 107:729–732PubMedCrossRef
9.
Zurück zum Zitat Ong P, Athanasiadis A, Sechtem U (2013) Patterns of coronary vasomotor responses to intracoronary acetylcholine provocation. Heart 99:1288–1295PubMedCrossRef Ong P, Athanasiadis A, Sechtem U (2013) Patterns of coronary vasomotor responses to intracoronary acetylcholine provocation. Heart 99:1288–1295PubMedCrossRef
10.
Zurück zum Zitat Ong P, Athanasiadis A, Borgulya G, Mahrholdt H, Kaski JC, Sechtem U (2012) High prevalence of a pathological response to acetylcholine testing in patients with stable angina pectoris and unobstructed coronary arteries. The ACOVA Study (Abnormal COronary VAsomotion in patients with stable angina and unobstructed coronary arteries). J Am Coll Cardiol. 59:655–662PubMedCrossRef Ong P, Athanasiadis A, Borgulya G, Mahrholdt H, Kaski JC, Sechtem U (2012) High prevalence of a pathological response to acetylcholine testing in patients with stable angina pectoris and unobstructed coronary arteries. The ACOVA Study (Abnormal COronary VAsomotion in patients with stable angina and unobstructed coronary arteries). J Am Coll Cardiol. 59:655–662PubMedCrossRef
11.
Zurück zum Zitat Montone RA, Niccoli G, Fracassi F, Russo M, Gurgoglione F, Cammà G, Lanza GA, Crea F (2018) Patients with acute myocardial infarction and non-obstructive coronary arteries: safety and prognostic relevance of invasive coronary provocative tests. Eur Heart J 39:91–98PubMed Montone RA, Niccoli G, Fracassi F, Russo M, Gurgoglione F, Cammà G, Lanza GA, Crea F (2018) Patients with acute myocardial infarction and non-obstructive coronary arteries: safety and prognostic relevance of invasive coronary provocative tests. Eur Heart J 39:91–98PubMed
12.
Zurück zum Zitat Aziz A, Hansen HS, Sechtem U, Prescott E, Ong P (2017) Sex-related differences in vasomotor function in patients with angina and unobstructed coronary arteries. J Am Coll Cardiol 70:2349–2358PubMedCrossRef Aziz A, Hansen HS, Sechtem U, Prescott E, Ong P (2017) Sex-related differences in vasomotor function in patients with angina and unobstructed coronary arteries. J Am Coll Cardiol 70:2349–2358PubMedCrossRef
13.
Zurück zum Zitat Ong P, Athanasiadis A, Borgulya G, Vokshi I, Bastiaenen R, Kubik S, Hill S, Schäufele T, Mahrholdt H, Kaski JC, Sechtem U (2014) Clinical usefulness, angiographic characteristics, and safety evaluation of intracoronary acetylcholine provocation testing among 921 consecutive white patients with unobstructed coronary arteries. Circulation 29(129):1723–1730CrossRef Ong P, Athanasiadis A, Borgulya G, Vokshi I, Bastiaenen R, Kubik S, Hill S, Schäufele T, Mahrholdt H, Kaski JC, Sechtem U (2014) Clinical usefulness, angiographic characteristics, and safety evaluation of intracoronary acetylcholine provocation testing among 921 consecutive white patients with unobstructed coronary arteries. Circulation 29(129):1723–1730CrossRef
14.
Zurück zum Zitat Lee EM, Choi MH, Seo HS, Kim HK, Kim NH, Choi CU, Kim JW, Lim HE, Kim EJ, Rha SW, Park CG, Oh DJ (2017) Impact of vasomotion type on prognosis of coronary artery spasm induced by acetylcholine provocation test of left coronary artery. Atherosclerosis. 257:195–200PubMedCrossRef Lee EM, Choi MH, Seo HS, Kim HK, Kim NH, Choi CU, Kim JW, Lim HE, Kim EJ, Rha SW, Park CG, Oh DJ (2017) Impact of vasomotion type on prognosis of coronary artery spasm induced by acetylcholine provocation test of left coronary artery. Atherosclerosis. 257:195–200PubMedCrossRef
15.
Zurück zum Zitat 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. 38:2565–2568PubMed 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. 38:2565–2568PubMed
16.
Zurück zum Zitat Ong P, Camici PG, Beltrame JF, Crea F, Shimokawa H, Sechtem U, Kaski JC, Bairey Merz CN, Coronary Vasomotion Disorders International Study Group (COVADIS) (2018) International standardization of diagnostic criteria for microvascular angina. Int J Cardiol. 250:16–20PubMedCrossRef Ong P, Camici PG, Beltrame JF, Crea F, Shimokawa H, Sechtem U, Kaski JC, Bairey Merz CN, Coronary Vasomotion Disorders International Study Group (COVADIS) (2018) International standardization of diagnostic criteria for microvascular angina. Int J Cardiol. 250:16–20PubMedCrossRef
18.
Zurück zum Zitat Nagueh SF, Smiseth OA, Appleton CP, Byrd BF 3rd, Dokainish H, Edvardsen T, Flachskampf FA, Gillebert TC, Klein AL, Lancellotti P, Marino P, Oh JK, Popescu B, Waggoner AD (2016) Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the american society of echocardiography and the European Association Of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 17:1321–1360PubMedCrossRef Nagueh SF, Smiseth OA, Appleton CP, Byrd BF 3rd, Dokainish H, Edvardsen T, Flachskampf FA, Gillebert TC, Klein AL, Lancellotti P, Marino P, Oh JK, Popescu B, Waggoner AD (2016) Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the american society of echocardiography and the European Association Of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 17:1321–1360PubMedCrossRef
19.
Zurück zum Zitat Khoury S, Steinvil A, Gal-Oz A, Margolis G, Hochstatd A, Topilsky Y, Keren G, Shacham Y (2018) Association between central venous pressure as assessed by echocardiography, left ventricular function and acute cardio-renal syndrome in patients with ST segment elevation myocardial infarction. Clin Res Cardiol 107:937–944PubMedCrossRef Khoury S, Steinvil A, Gal-Oz A, Margolis G, Hochstatd A, Topilsky Y, Keren G, Shacham Y (2018) Association between central venous pressure as assessed by echocardiography, left ventricular function and acute cardio-renal syndrome in patients with ST segment elevation myocardial infarction. Clin Res Cardiol 107:937–944PubMedCrossRef
20.
Zurück zum Zitat Shaw LJ, Merz CN, Pepine CJ, Reis SE, Bittner V, Kelsey SF, Olson M, Johnson BD, Mankad S, Sharaf BL, Rogers WJ, Wessel TR, Arant CB, Pohost GM, Lerman A, Quyyumi AA, Sopko G, WISE Investigators (2006) Insights from the NHLBI-sponsored Women’s ischemia syndrome evaluation (WISE) Study: Part I: gender differences in traditional and novel risk factors, symptom evaluation, and gender-optimized diagnostic strategies. J Am Coll Cardiol. 47:S4–S20PubMedCrossRef Shaw LJ, Merz CN, Pepine CJ, Reis SE, Bittner V, Kelsey SF, Olson M, Johnson BD, Mankad S, Sharaf BL, Rogers WJ, Wessel TR, Arant CB, Pohost GM, Lerman A, Quyyumi AA, Sopko G, WISE Investigators (2006) Insights from the NHLBI-sponsored Women’s ischemia syndrome evaluation (WISE) Study: Part I: gender differences in traditional and novel risk factors, symptom evaluation, and gender-optimized diagnostic strategies. J Am Coll Cardiol. 47:S4–S20PubMedCrossRef
21.
Zurück zum Zitat Humphries KH, Izadnegahdar M, Sedlak T, Saw J, Johnston N, Schenck-Gustafsson K, Shah RU, Regitz-Zagrosek V, Grewal J, Vaccarino V, Wei J, Merz CN (2017) Sex differences in cardiovascular disease—impact on care and outcomes. Front Neuroendocrinol 46:46–70PubMedPubMedCentralCrossRef Humphries KH, Izadnegahdar M, Sedlak T, Saw J, Johnston N, Schenck-Gustafsson K, Shah RU, Regitz-Zagrosek V, Grewal J, Vaccarino V, Wei J, Merz CN (2017) Sex differences in cardiovascular disease—impact on care and outcomes. Front Neuroendocrinol 46:46–70PubMedPubMedCentralCrossRef
22.
Zurück zum Zitat Ong P, Athanasiadis A, Sechtem U (2013) Gender aspects in patients with angina and unobstructed coronary arteries. Clin Res Cardiol Suppl 8:25–31CrossRef Ong P, Athanasiadis A, Sechtem U (2013) Gender aspects in patients with angina and unobstructed coronary arteries. Clin Res Cardiol Suppl 8:25–31CrossRef
23.
Zurück zum Zitat Waits GS, O’Neal WT, Sandesara PB, Li Y, Shah AJ, Soliman EZ (2018) Association between low diastolic blood pressure and subclinical myocardial injury. Clin Res Cardiol 107:312–318PubMedCrossRef Waits GS, O’Neal WT, Sandesara PB, Li Y, Shah AJ, Soliman EZ (2018) Association between low diastolic blood pressure and subclinical myocardial injury. Clin Res Cardiol 107:312–318PubMedCrossRef
24.
Zurück zum Zitat Paul TK, Sivanesan K, Schulman-Marcus J (2017) Sex differences in nonobstructive coronary artery disease: recent insights and substantial knowledge gaps. Trends Cardiovasc Med 27:173–179PubMedCrossRef Paul TK, Sivanesan K, Schulman-Marcus J (2017) Sex differences in nonobstructive coronary artery disease: recent insights and substantial knowledge gaps. Trends Cardiovasc Med 27:173–179PubMedCrossRef
25.
Zurück zum Zitat Kitzman DW, Scholz DG, Hagen PT, Ilstrup DM, Edwards WD (1988) Age-related changes in normal human hearts during the first 10 decades of life. Part II (Maturity): a quantitative anatomic study of 765 specimens from subjects 20 to 99 years old. Mayo Clin Proc 63:137–146PubMedCrossRef Kitzman DW, Scholz DG, Hagen PT, Ilstrup DM, Edwards WD (1988) Age-related changes in normal human hearts during the first 10 decades of life. Part II (Maturity): a quantitative anatomic study of 765 specimens from subjects 20 to 99 years old. Mayo Clin Proc 63:137–146PubMedCrossRef
26.
Zurück zum Zitat Paulsen S, Vetner M, Hagerup LM (1975) Relationship between heart weight and the cross sectional area of the coronary ostia. Acta Pathol Microbiol Scand A Pathol 83:429–432 Paulsen S, Vetner M, Hagerup LM (1975) Relationship between heart weight and the cross sectional area of the coronary ostia. Acta Pathol Microbiol Scand A Pathol 83:429–432
27.
Zurück zum Zitat Koizumi T, Yokoyama M, Namikawa S, Kuriyama N, Nameki M, Nakayama T, Kaneda H, Sudhir K, Yock PG, Komiyama N, Fitzgerald PJ (2006) Location of focal vasospasm provoked by ergonovine maleate within coronary arteries in patients with vasospastic angina pectoris. Am J Cardiol 97:1322–1325PubMedCrossRef Koizumi T, Yokoyama M, Namikawa S, Kuriyama N, Nameki M, Nakayama T, Kaneda H, Sudhir K, Yock PG, Komiyama N, Fitzgerald PJ (2006) Location of focal vasospasm provoked by ergonovine maleate within coronary arteries in patients with vasospastic angina pectoris. Am J Cardiol 97:1322–1325PubMedCrossRef
28.
Zurück zum Zitat Yamagishi M, Miyatake K, Tamai J, Nakatani S, Koyama J, Nissen SE (1994) Intravascular ultrasound detection of atherosclerosis at the site of focal vasospasm in angiographically normal or minimally narrowed coronary segments. J Am Coll Cardiol 23:352–357PubMedCrossRef Yamagishi M, Miyatake K, Tamai J, Nakatani S, Koyama J, Nissen SE (1994) Intravascular ultrasound detection of atherosclerosis at the site of focal vasospasm in angiographically normal or minimally narrowed coronary segments. J Am Coll Cardiol 23:352–357PubMedCrossRef
29.
30.
Zurück zum Zitat Arrebola-Moreno AL, Arrebola JP, Moral-Ruiz A, Ramirez-Hernandez JA, Melgares-Moreno R, Kaski JC (2014) Coronary microvascular spasm triggers transient ischemic left ventricular diastolic abnormalities in patients with chest pain and angiographically normal coronary arteries. Atherosclerosis. 236:207–214PubMedCrossRef Arrebola-Moreno AL, Arrebola JP, Moral-Ruiz A, Ramirez-Hernandez JA, Melgares-Moreno R, Kaski JC (2014) Coronary microvascular spasm triggers transient ischemic left ventricular diastolic abnormalities in patients with chest pain and angiographically normal coronary arteries. Atherosclerosis. 236:207–214PubMedCrossRef
31.
Zurück zum Zitat Ong P, Athanasiadis A, Mahrholdt H, Shah BN, Sechtem U, Senior R (2013) Transient myocardial ischemia during acetylcholine-induced coronary microvascular dysfunction documented by myocardial contrast echocardiography. Circ Cardiovasc Imaging 6:153–155PubMedCrossRef Ong P, Athanasiadis A, Mahrholdt H, Shah BN, Sechtem U, Senior R (2013) Transient myocardial ischemia during acetylcholine-induced coronary microvascular dysfunction documented by myocardial contrast echocardiography. Circ Cardiovasc Imaging 6:153–155PubMedCrossRef
32.
Zurück zum Zitat Taqueti VR, Solomon SD, Shah AM, Desai AS, Groarke JD, Osborne MT, Hainer J, Bibbo CF, Dorbala S, Blankstein R, Di Carli MF (2018) Coronary microvascular dysfunction and future risk of heart failure with preserved ejection fraction. Eur Heart J 39:840–849PubMedCrossRef Taqueti VR, Solomon SD, Shah AM, Desai AS, Groarke JD, Osborne MT, Hainer J, Bibbo CF, Dorbala S, Blankstein R, Di Carli MF (2018) Coronary microvascular dysfunction and future risk of heart failure with preserved ejection fraction. Eur Heart J 39:840–849PubMedCrossRef
33.
Zurück zum Zitat Crea F, Bairey Merz CN, Beltrame JF, Kaski JC, Ogawa H, Ong P, Sechtem U, Shimokawa H, Camici PG, Coronary Vasomotion Disorders International Study Group (COVADIS) (2017) The parallel tales of microvascular angina and heart failure with preserved ejection fraction: a paradigm shift. Eur Heart J. 38:473–477PubMed Crea F, Bairey Merz CN, Beltrame JF, Kaski JC, Ogawa H, Ong P, Sechtem U, Shimokawa H, Camici PG, Coronary Vasomotion Disorders International Study Group (COVADIS) (2017) The parallel tales of microvascular angina and heart failure with preserved ejection fraction: a paradigm shift. Eur Heart J. 38:473–477PubMed
34.
Zurück zum Zitat Bohnen S, Prüβner L, Vettorazzi E, Radunski UK, Tahir E, Schneider J, Cavus E, Avanesov M, Stehning C, Adam G, Blankenberg S, Lund GK, Muellerleile K (2019) Stress T1-mapping cardiovascular magnetic resonance imaging and inducible myocardial ischemia. Clin Res Cardiol. https://doi.org/10.1007/s00392-019-01421-1(Epub ahead of print)PubMedCrossRef Bohnen S, Prüβner L, Vettorazzi E, Radunski UK, Tahir E, Schneider J, Cavus E, Avanesov M, Stehning C, Adam G, Blankenberg S, Lund GK, Muellerleile K (2019) Stress T1-mapping cardiovascular magnetic resonance imaging and inducible myocardial ischemia. Clin Res Cardiol. https://​doi.​org/​10.​1007/​s00392-019-01421-1(Epub ahead of print)PubMedCrossRef
35.
Zurück zum Zitat Tiwari S, Schirmer H, Jacobsen BK, Hopstock LA, Nyrnes A, Heggelund G, Njølstad I, Mathiesen EB, Løchen ML (2015) Association between diastolic dysfunction and future atrial fibrillation in the Tromsø Study from 1994 to 2010. Heart 101:1302–1308PubMedCrossRef Tiwari S, Schirmer H, Jacobsen BK, Hopstock LA, Nyrnes A, Heggelund G, Njølstad I, Mathiesen EB, Løchen ML (2015) Association between diastolic dysfunction and future atrial fibrillation in the Tromsø Study from 1994 to 2010. Heart 101:1302–1308PubMedCrossRef
Metadaten
Titel
Clinical, angiographic and echocardiographic correlates of epicardial and microvascular spasm in patients with myocardial ischaemia and non-obstructive coronary arteries
verfasst von
Rocco Antonio Montone
Giampaolo Niccoli
Michele Russo
Marta Giaccari
Marco Giuseppe Del Buono
Maria Chiara Meucci
Filippo Gurgoglione
Rocco Vergallo
Domenico D’Amario
Antonino Buffon
Antonio M. Leone
Francesco Burzotta
Cristina Aurigemma
Carlo Trani
Giovanna Liuzzo
Gaetano A. Lanza
Filippo Crea
Publikationsdatum
03.07.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Clinical Research in Cardiology / Ausgabe 4/2020
Print ISSN: 1861-0684
Elektronische ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-019-01523-w

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