Skip to main content
Top
Published in: Heart and Vessels 3/2021

01-03-2021 | Original Article

Assessment of coronary vasomotor responses to acetylcholine in German and Japanese patients with epicardial coronary spasm—more similarities than differences?

Authors: Akira Suda, Andreas Seitz, Yuji Odaka, Anastasios Athanasiadis, Giancarlo Pirozzolo, Koichi Sato, Kiyotaka Hao, Raffi Bekeredjian, Jun Takahashi, Udo Sechtem, Hiroaki Shimokawa, Peter Ong

Published in: Heart and Vessels | Issue 3/2021

Login to get access

Abstract

Coronary spasm is an established cause for angina pectoris. Ethnic differences have been suggested among Asian compared to Caucasian patients regarding prevalence, gender distribution, and angiographic patterns of coronary spasm. The aim of this study was to compare contemporary German and Japanese patients with coronary spasm. Between 2011 and 2015, 149 patients with resting angina and unobstructed coronary arteries with acetylcholine-induced epicardial spasm were enrolled in Stuttgart, Germany (n = 69) and Sendai, Japan (n = 80). All patients underwent intracoronary acetylcholine testing according to a standardized protocol. Comprehensive analysis included type of spasm (focal/diffuse), dose of acetylcholine leading to spasm, and frequency of multivessel spasm. Patients in this study were 61 ± 11 years old, predominantly female (54%), and had normal left ventricular ejection fraction (73 ± 9%). Diffuse spasm was the most prevalent type of spasm (85%) whereas focal spasm was found in the remaining 15% of patients. 31% of patients had multivessel spasm. Comparing the German with the Japanese patients, distribution of spasm type (focal/diffuse, p = 0.19) and frequency of multivessel spasm (p = 0.22) were comparable. Moreover, when Japanese patients were compared with German patients and diffuse spasm with focal spasm patients, respectively, no significant differences were observed regarding the acetylcholine dose required to induce spasm (p = 0.078 and p = 0.46, respectively). In conclusion, diffuse epicardial coronary spasm is the most frequent finding among German and Japanese patients with resting angina, unobstructed coronary arteries, and epicardial spasm on acetylcholine testing. Japanese and German patients share several similarities including comparable types of spasm and frequency of multivessel spasm.

Graphical abstract

Literature
1.
go back to reference JCS Joint Working Group (2010) Guidelines for diagnosis and treatment of patients with vasospastic angina (coronary spastic angina) (JCS 2008). Circ J 74:1745–1762CrossRef JCS Joint Working Group (2010) Guidelines for diagnosis and treatment of patients with vasospastic angina (coronary spastic angina) (JCS 2008). Circ J 74:1745–1762CrossRef
2.
go back to reference Beltrame JF, Crea F, Kaski JC, Ogawa H, Ong P, Sechtem U, Shimokawa H, Bairey Merz CN, Coronary Vasomotion Disorders International Study G (2016) The who, what, why, when, how and where of vasospastic angina. Circ J 80:289–298CrossRef Beltrame JF, Crea F, Kaski JC, Ogawa H, Ong P, Sechtem U, Shimokawa H, Bairey Merz CN, Coronary Vasomotion Disorders International Study G (2016) The who, what, why, when, how and where of vasospastic angina. Circ J 80:289–298CrossRef
3.
go back to reference Shimokawa H (2014) 2014 Williams Harvey Lecture: importance of coronary vasomotion abnormalities-from bench to bedside. Eur Heart J 35:3180–3193CrossRef Shimokawa H (2014) 2014 Williams Harvey Lecture: importance of coronary vasomotion abnormalities-from bench to bedside. Eur Heart J 35:3180–3193CrossRef
4.
go back to reference 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 59:655–662CrossRef 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 59:655–662CrossRef
5.
go back to reference Bairey Merz CN, Pepine CJ, Walsh MN, Fleg JL (2017) Ischemia and no obstructive coronary artery disease (INOCA): developing evidence-based therapies and research agenda for the next decade. Circulation 135:1075–1092CrossRef Bairey Merz CN, Pepine CJ, Walsh MN, Fleg JL (2017) Ischemia and no obstructive coronary artery disease (INOCA): developing evidence-based therapies and research agenda for the next decade. Circulation 135:1075–1092CrossRef
6.
go back to reference 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 131:861–870CrossRef 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 131:861–870CrossRef
7.
go back to reference Montone RA, Niccoli G, Fracassi F, Russo M, Gurgoglione F, Camma 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, Camma 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
8.
go back to reference Ong P, Athanasiadis A, Sechtem U (2013) Patterns of coronary vasomotor responses to intracoronary acetylcholine provocation. Heart 99:1288–1295CrossRef Ong P, Athanasiadis A, Sechtem U (2013) Patterns of coronary vasomotor responses to intracoronary acetylcholine provocation. Heart 99:1288–1295CrossRef
9.
go back to reference Beltrame JF, Crea F, Kaski JC, Ogawa H, Ong P, Sechtem U, Shimokawa H, Bairey Merz CN, Coronary Vasomotion Disorders International Study G (2017) International standardization of diagnostic criteria for vasospastic angina. Eur Heart J 38:2565–2568 Beltrame JF, Crea F, Kaski JC, Ogawa H, Ong P, Sechtem U, Shimokawa H, Bairey Merz CN, Coronary Vasomotion Disorders International Study G (2017) International standardization of diagnostic criteria for vasospastic angina. Eur Heart J 38:2565–2568
10.
go back to reference Ciliberti G, Seshasai SRK, Ambrosio G, Kaski JC (2017) Safety of intracoronary provocative testing for the diagnosis of coronary artery spasm. Int J Cardiol 244:77–83CrossRef Ciliberti G, Seshasai SRK, Ambrosio G, Kaski JC (2017) Safety of intracoronary provocative testing for the diagnosis of coronary artery spasm. Int J Cardiol 244:77–83CrossRef
11.
go back to reference Beltrame JF, Sasayama S, Maseri A (1999) Racial heterogeneity in coronary artery vasomotor reactivity: differences between Japanese and Caucasian patients. J Am Coll Cardiol 33:1442–1452CrossRef Beltrame JF, Sasayama S, Maseri A (1999) Racial heterogeneity in coronary artery vasomotor reactivity: differences between Japanese and Caucasian patients. J Am Coll Cardiol 33:1442–1452CrossRef
12.
go back to reference Pristipino C, Beltrame JF, Finocchiaro ML, Hattori R, Fujita M, Mongiardo R, Cianflone D, Sanna T, Sasayama S, Maseri A (2000) Major racial differences in coronary constrictor response between Japanese and Caucasians with recent myocardial infarction. Circulation 101:1102–1108CrossRef Pristipino C, Beltrame JF, Finocchiaro ML, Hattori R, Fujita M, Mongiardo R, Cianflone D, Sanna T, Sasayama S, Maseri A (2000) Major racial differences in coronary constrictor response between Japanese and Caucasians with recent myocardial infarction. Circulation 101:1102–1108CrossRef
13.
go back to reference Sueda S, Ochi N, Kawada H, Matsuda S, Hayashi Y, Tsuruoka T, Uraoka T (1999) Frequency of provoked coronary vasospasm in patients undergoing coronary arteriography with spasm provocation test of acetylcholine. Am J Cardiol 83:1186–1190CrossRef Sueda S, Ochi N, Kawada H, Matsuda S, Hayashi Y, Tsuruoka T, Uraoka T (1999) Frequency of provoked coronary vasospasm in patients undergoing coronary arteriography with spasm provocation test of acetylcholine. Am J Cardiol 83:1186–1190CrossRef
14.
go back to reference Sato K, Takahashi J, Odaka Y, Suda A, Sueda S, Teragawa H, Ishii K, Kiyooka T, Hirayama A, Sumiyoshi T, Tanabe Y, Kimura K, Kaikita K, Ong P, Sechtem U, Camici PG, Kaski JC, Crea F, Beltrame JF, Shimokawa H, Japanese Coronary Spasm A (2019) Clinical characteristics and long-term prognosis of contemporary patients with vasospastic angina: ethnic differences detected in an international comparative study. Int J Cardiol 291:13–18CrossRef Sato K, Takahashi J, Odaka Y, Suda A, Sueda S, Teragawa H, Ishii K, Kiyooka T, Hirayama A, Sumiyoshi T, Tanabe Y, Kimura K, Kaikita K, Ong P, Sechtem U, Camici PG, Kaski JC, Crea F, Beltrame JF, Shimokawa H, Japanese Coronary Spasm A (2019) Clinical characteristics and long-term prognosis of contemporary patients with vasospastic angina: ethnic differences detected in an international comparative study. Int J Cardiol 291:13–18CrossRef
15.
go back to reference Takagi Y, Yasuda S, Takahashi J, Tsunoda R, Ogata Y, Seki A, Sumiyoshi T, Matsui M, Goto T, Tanabe Y, Sueda S, Sato T, Ogawa S, Kubo N, Momomura S, Ogawa H, Shimokawa H, Japanese Coronary Spasm A (2013) Clinical implications of provocation tests for coronary artery spasm: safety, arrhythmic complications, and prognostic impact: multicentre registry study of the Japanese Coronary Spasm Association. Eur Heart J 34:258–267CrossRef Takagi Y, Yasuda S, Takahashi J, Tsunoda R, Ogata Y, Seki A, Sumiyoshi T, Matsui M, Goto T, Tanabe Y, Sueda S, Sato T, Ogawa S, Kubo N, Momomura S, Ogawa H, Shimokawa H, Japanese Coronary Spasm A (2013) Clinical implications of provocation tests for coronary artery spasm: safety, arrhythmic complications, and prognostic impact: multicentre registry study of the Japanese Coronary Spasm Association. Eur Heart J 34:258–267CrossRef
16.
go back to reference 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 52:523–527CrossRef 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 52:523–527CrossRef
17.
go back to reference JCS Joint Working Group (2014) Guidelines for diagnosis and treatment of patients with vasospastic angina (Coronary Spastic Angina) (JCS 2013). Circ J 78:2779–2801CrossRef JCS Joint Working Group (2014) Guidelines for diagnosis and treatment of patients with vasospastic angina (Coronary Spastic Angina) (JCS 2013). Circ J 78:2779–2801CrossRef
18.
go back to reference Mohri M, Koyanagi M, Egashira K, Tagawa H, Ichiki T, Shimokawa H, Takeshita A (1998) Angina pectoris caused by coronary microvascular spasm. Lancet 351:1165–1169CrossRef Mohri M, Koyanagi M, Egashira K, Tagawa H, Ichiki T, Shimokawa H, Takeshita A (1998) Angina pectoris caused by coronary microvascular spasm. Lancet 351:1165–1169CrossRef
19.
go back to reference Austen WG, Edwards JE, Frye RL, Gensini GG, Gott VL, Griffith LS, McGoon DC, Murphy ML, Roe BB (1975) A reporting system on patients evaluated for coronary artery disease. Report of the Ad Hoc committee for grading of coronary artery disease, council on cardiovascular surgery, American Heart Association. Circulation 51:5–40CrossRef Austen WG, Edwards JE, Frye RL, Gensini GG, Gott VL, Griffith LS, McGoon DC, Murphy ML, Roe BB (1975) A reporting system on patients evaluated for coronary artery disease. Report of the Ad Hoc committee for grading of coronary artery disease, council on cardiovascular surgery, American Heart Association. Circulation 51:5–40CrossRef
20.
go back to reference 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 70:2349–2358CrossRef 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 70:2349–2358CrossRef
21.
go back to reference Robinson D, Kawamura T, Hinohara S, Sakamoto Y, Takahashi T (1995) Levels of cardiovascular risk factors in Japanese people living in the UK. J Cardiovasc Risk 2:449–458CrossRef Robinson D, Kawamura T, Hinohara S, Sakamoto Y, Takahashi T (1995) Levels of cardiovascular risk factors in Japanese people living in the UK. J Cardiovasc Risk 2:449–458CrossRef
22.
go back to reference Ong P, Pirozzolo G, Athanasiadis A, Sechtem U (2018) Epicardial coronary spasm in women with angina pectoris and unobstructed coronary arteries is linked with a positive family history: an observational study. Clin Ther 40:1584–1590CrossRef Ong P, Pirozzolo G, Athanasiadis A, Sechtem U (2018) Epicardial coronary spasm in women with angina pectoris and unobstructed coronary arteries is linked with a positive family history: an observational study. Clin Ther 40:1584–1590CrossRef
23.
go back to reference Takefuji M, Asano H, Mori K, Amano M, Kato K, Watanabe T, Morita Y, Katsumi A, Itoh T, Takenawa T, Hirashiki A, Izawa H, Nagata K, Hirayama H, Takatsu F, Naoe T, Yokota M, Kaibuchi K (2010) Mutation of ARHGAP9 in patients with coronary spastic angina. J Hum Genet 55:42–49CrossRef Takefuji M, Asano H, Mori K, Amano M, Kato K, Watanabe T, Morita Y, Katsumi A, Itoh T, Takenawa T, Hirashiki A, Izawa H, Nagata K, Hirayama H, Takatsu F, Naoe T, Yokota M, Kaibuchi K (2010) Mutation of ARHGAP9 in patients with coronary spastic angina. J Hum Genet 55:42–49CrossRef
Metadata
Title
Assessment of coronary vasomotor responses to acetylcholine in German and Japanese patients with epicardial coronary spasm—more similarities than differences?
Authors
Akira Suda
Andreas Seitz
Yuji Odaka
Anastasios Athanasiadis
Giancarlo Pirozzolo
Koichi Sato
Kiyotaka Hao
Raffi Bekeredjian
Jun Takahashi
Udo Sechtem
Hiroaki Shimokawa
Peter Ong
Publication date
01-03-2021
Publisher
Springer Japan
Published in
Heart and Vessels / Issue 3/2021
Print ISSN: 0910-8327
Electronic ISSN: 1615-2573
DOI
https://doi.org/10.1007/s00380-020-01707-9

Other articles of this Issue 3/2021

Heart and Vessels 3/2021 Go to the issue