Abstract
Patients with epicardial coronary vasospastic angina (VSA) may be likely to have coronary microvascular dysfunction, although mixed results have been reported. The aim of this study was to evaluate coronary microvascular function in detail using novel invasive physiologic indices, such as resistive reserve ratio (RRR) and microvascular resistance reserve (MRR). A total of 45 patients undergoing intracoronary acetylcholine (ACh) provocation test and invasive coronary circulatory evaluation using a thermodilution method were prospectively included. VSA was diagnosed as angiographic vasospasm accompanied by chest pain and/or ischemic electrocardiographic changes by intracoronary injection of ACh. Coronary circulation was assessed with physiologic indices including fractional flow reserve, resting and hyperemic mean transit time (Tmn), coronary flow reserve (CFR), basal resistance index, index of microcirculatory resistance (IMR), RRR, and MRR. Of 45 patients, 23 (51.1%) were diagnosed as having VSA. Patients with positive ACh test had longer resting Tmn (slower coronary flow velocity), higher basal resistance index, and greater RRR and MRR than those without, while fractional flow reserve, CFR, and IMR did not differ significantly between the two groups. In conclusion, although conventional measures such as CFR and IMR failed to show significant differences, RRR and MRR, novel invasive coronary physiologic indices, provided counterintuitive insights that coronary microvascular dilation function was better preserved in patients with VSA than those without.
Similar content being viewed by others
References
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 135:1075–1092
Ford TJ, Stanley B, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, Yii E, Sidik N, McCartney P, Corcoran D, Collison D, Rush C, McConnachie A, Touyz RM, Oldroyd KG, Berry C (2018) Stratified medical therapy using invasive coronary function testing in angina: the CorMicA Trial. J Am Coll Cardiol 72:2841–2855
Kunadian V, Chieffo A, Camici PG, Berry C, Escaned J, Maas AHEM, Prescott E, Karam N, Appelman Y, Fraccaro C, Louise Buchanan G, Manzo-Silberman S, Al-Lamee R, Regar E, Lansky A, Abbott JD, Badimon L, Duncker DJ, Mehran R, Capodanno D, Baumbach A (2020) An EAPCI expert consensus document on ischaemia with non-obstructive coronary arteries in collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology and Microcirculation endorsed by Coronary Vasomotor Disorders International Study Group. Eur Heart J 41:3504–3520
Saito Y, Kitahara H, Nishi T, Fujimoto Y, Kobayashi Y (2019) Decreased resting coronary flow and impaired endothelial function in patients with vasospastic angina. Coron Artery Dis 30:291–296
Suda A, Takahashi J, Hao K, Kikuchi Y, Shindo T, Ikeda S, Sato K, Sugisawa J, Matsumoto Y, Miyata S, Sakata Y, Shimokawa H (2019) Coronary functional abnormalities in patients with angina and nonobstructive coronary artery disease. J Am Coll Cardiol 74:2350–2360
Pirozzolo G, Martínez Pereyra V, Hubert A, Guenther F, Sechtem U, Bekeredjian R, Mahrholdt H, Ong P, Seitz A (2021) Coronary artery spasm and impaired myocardial perfusion in patients with ANOCA: predictors from a multimodality study using stress CMR and acetylcholine testing. Int J Cardiol 343:5–11
Takagi A, Arai K, Hosaka M, Komatsu Y, Gunnji K, Tanimoto K, Ishizuka N, Tsurumi Y, Hagiwara N (2008) Noninvasive prediction of angiographic spasm provocation using trans-thoracic Doppler echocardiography in patients with coronary spastic angina. Circ J 72:1640–1644
Yamanaga K, Tsujita K, Komura N, Kaikita K, Sakamoto K, Miyazaki T, Saito M, Ishii M, Tabata N, Akasaka T, Sato K, Horio E, Arima Y, Kojima S, Tayama S, Nakamura S, Hokimoto S, Ogawa H (2015) Single-wire pressure and flow velocity measurement for quantifying microvascular dysfunction in patients with coronary vasospastic angina. Am J Physiol Heart Circ Physiol 308:H478–H484
Ford TJ, Yii E, Sidik N, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, McCartney P, Corcoran D, Collison D, Rush C, Stanley B, McConnachie A, Sattar N, Touyz RM, Oldroyd KG, Berry C (2019) Ischemia and no obstructive coronary artery disease: prevalence and correlates of coronary vasomotion disorders. Circ Cardiovasc Interv 12:e008126
Konst RE, Damman P, Pellegrini D, Hartzema-Meijer MJ, van Uden BJC, Jansen TPJ, Brandsma J, Vart P, Gehlmann H, Maas AHEM, van Royen N, Elias-Smale SE (2021) Vasomotor dysfunction in patients with angina and nonobstructive coronary artery disease is dominated by vasospasm. Int J Cardiol 333:14–20
Maznyczka AM, Oldroyd KG, Greenwood JP, McCartney PJ, Cotton J, Lindsay M, McEntegart M, Rocchiccioli JP, Good R, Robertson K, Eteiba H, Watkins S, Shaukat A, Petrie CJ, Murphy A, Petrie MC, Berry C (2020) Comparative significance of invasive measures of microvascular injury in acute myocardial infarction. Circ Cardiovasc Interv 13:e008505
Lee SH, Lee JM, Park J, Choi KH, Hwang D, Doh JH, Nam CW, Shin ES, Hoshino M, Murai T, Yonetsu T, Mejía-Rentería H, Kakuta T, Escaned J, International Collaboration of Comprehensive Physiologic Assessment Investigators (2020) Prognostic implications of resistive reserve ratio in patients with coronary artery disease. J Am Heart Assoc 9:e015846
Toya T, Ahmad A, Corban MT, Ӧzcan I, Sara JD, Sebaali F, Escaned J, Lerman LO, Lerman A (2021) Risk stratification of patients with nonobstructive coronary artery disease using resistive reserve ratio. J Am Heart Assoc 10:e020464
De Bruyne B, Pijls NHJ, Gallinoro E, Candreva A, Fournier S, Keulards DCJ, Sonck J, Van’t Veer M, Barbato E, Bartunek J, Vanderheyden M, Wyffels E, De Vos A, El Farissi M, Tonino PAL, Muller O, Collet C, Fearon WF (2021) Microvascular resistance reserve for assessment of coronary microvascular function: JACC technology corner. J Am Coll Cardiol 78:1541–1549
Jansen TPJ, Konst RE, Elias-Smale SE, van den Oord SC, Ong P, de Vos AMJ, van de Hoef TP, Paradies V, Smits PC, van Royen N, Damman P (2021) Assessing microvascular dysfunction in angina with unobstructed coronary arteries: JACC review topic of the week. J Am Coll Cardiol 78:1471–1479
Saito Y, Kitahara H, Nishi T, Fujimoto Y, Kobayashi Y (2020) Systemic endothelial dysfunction in patients with vasospastic and microvascular angina: serum uric acid as a marker of reactive hyperemia index. Coron Artery Dis 31:565–566
JCS Joint Working Group (2014) Guidelines for diagnosis and treatment of patients with vasospastic angina (Coronary Spastic Angina) (JCS 2013). Circ J 78:2779–2801
Suzuki S, Kaikita K, Yamamoto E, Jinnouchi H, Tsujita K (2021) Role of acetylcholine spasm provocation test as a pathophysiological assessment in nonobstructive coronary artery disease. Cardiovasc Interv Ther 36:39–51
Matsumoto T, Saito Y, Saito K, Tateishi K, Kato K, Kitahara H, Kobayashi Y (2021) Relation between cancer and vasospastic angina. Adv Ther 38:4344–4353
Tateishi K, Saito Y, Kitahara H, Shoji T, Kadohira T, Nakayama T, Fujimoto Y, Kobayashi Y (2018) Safety and usefulness of acetylcholine provocation test in patients with no culprit lesions on emergency coronary angiography. Int J Cardiol 269:27–30
Saito Y, Kitahara H, Shoji T, Tokimasa S, Nakayama T, Sugimoto K, Fujimoto Y, Kobayashi Y (2017) Relation between severity of myocardial bridge and vasospasm. Int J Cardiol 248:34–38
Saito Y, Kitahara H, Shoji T, Tokimasa S, Nakayama T, Sugimoto K, Fujimoto Y, Kobayashi Y (2016) Intracoronary acetylcholine provocation testing—omission of the 20-µg dose is feasible in patients without coronary artery spasm in the other coronary artery. Circ J 80:1820–1823
Sueda S, Kohno H (2020) Transitional changes of acetylcholine spasm provocation test procedures. Cardiovasc Interv Ther 35:321–326
Kawase Y, Matsuo H, Akasaka T, Shiono Y, Tanaka N, Amano T, Kozuma K, Nakamura M, Yokoi H, Kobayashi Y, Ikari Y (2019) Clinical use of physiological lesion assessment using pressure guidewires: an expert consensus document of the Japanese Association of Cardiovascular Intervention and Therapeutics. Cardiovasc Interv Ther 34:85–96
Nishi T, Kitahara H, Saito Y, Nishi T, Nakayama T, Fujimoto Y, Matsumiya G, Kobayashi Y (2018) Invasive assessment of microvascular function in patients with valvular heart disease. Coron Artery Dis 29:223–229
Yong AS, Layland J, Fearon WF, Ho M, Shah MG, Daniels D, Whitbourn R, Macisaac A, Kritharides L, Wilson A, Ng MK (2013) Calculation of the index of microcirculatory resistance without coronary wedge pressure measurement in the presence of epicardial stenosis. JACC Cardiovasc Interv 6:53–58
van ‘t Veer M, Adjedj J, Wijnbergen I, Tóth GG, Rutten MC, Barbato E, van Nunen LX, Pijls NH, De Bruyne B (2016) Novel monorail infusion catheter for volumetric coronary blood flow measurement in humans: in vitro validation. EuroIntervention 12:701–707
Fearon WF, Kobayashi Y (2017) Invasive assessment of the coronary microvasculature: the index of microcirculatory resistance. Circ Cardiovasc Interv 10:e005361
Layland J, Carrick D, McEntegart M, Ahmed N, Payne A, McClure J, Sood A, McGeoch R, MacIsaac A, Whitbourn R, Wilson A, Oldroyd K, Berry C (2013) Vasodilatory capacity of the coronary microcirculation is preserved in selected patients with non-ST-segment-elevation myocardial infarction. Circ Cardiovasc Interv 6:231–236
Lee JM, Jung JH, Hwang D, Park J, Fan Y, Na SH, Doh JH, Nam CW, Shin ES, Koo BK (2016) Coronary flow reserve and microcirculatory resistance in patients with intermediate coronary stenosis. J Am Coll Cardiol 67:1158–1169
Sueda S (2020) Pharmacological spasm provocation testing in 2500 patients: provoked spasm incidence, complications and cardiac events. Heart Vessels 35:1368–1377
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 38:2565–2568
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Saito, Y., Nishi, T., Kato, K. et al. Resistive reserve ratio and microvascular resistance reserve in patients with coronary vasospastic angina. Heart Vessels 37, 1489–1495 (2022). https://doi.org/10.1007/s00380-022-02051-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00380-022-02051-w