Microvascular angina due to coronary microvascular dysfunction: pathophysiological mechanisms, diagnostic and treatment aspects
Abstract
The diagnosis of myocardial ischemia caused by coronary microvascular dysfunction (CMD), particularly the diagnosis of microvascular angina, has gained more prominence in recent decades. Despite patients with such a diagnosis having a higher risk of adverse cardiovascular events, including myocardial infarction, stroke, the onset and progression of heart failure, and death, there are currently no unified guidelines for the diagnosis and treatment of this nosology, and the management strategy for this group of patients largely remains empirical. The aim of this review is to examine the mechanisms underlying microvascular dysfunction, diagnostic criteria, and treatment methods for myocardial ischemia associated with microvascular dysfunction.
References
Likoff W., Segal B.L., Kasparian H. Paradox of normal selective coronary arteriograms in patients considered to have unmistakable coronary heart disease. N. Engl. J. Med. 1967; 276 (19): 1063–1066. DOI: 10.1056NEJM196705112761904
Kemp H., Vokonas P., Cohn P., Gorlin R. The anginal syndrome associated with normal coronary arteriograms. Report of a six year experience. Am. J. Med. 1973; 54 (6): 735–742. DOI: 10.1016/0002-9343(73)90060-0
Montalescot G., Sechtem U., Achenbach S., Andreotti F., Arden C., Budaj A. et al. 2013 ESC guidelines on the management of stable coronary artery disease. Eur. Heart J. 34 (38): 2949–3003. DOI: 10.1093/eurheartj/eht296
Knuuti J., Wijns W., Saraste A., Capodanno D., Barbato E., Funck-Brentano C. et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur. Heart J. 2019; 41 (3): 407–477. DOI: 10.1093/eurheartj/ehz425
Canu M., Khouri C., Marliere S., Vautrin E., Piliero N., Ormezzano O. et al. Prognostic significance of severe coronary microvascular dysfunction post-PCI in patients with STEMI: A systematic review and meta-analysis. PLoS One. 2022; 17 (5): e0268330. DOI: 10.1371/journal.pone.0268330
Feenstra R., Boerhou C., Woudstra J., Vink C., Wittekoek M., de Waard G. Presence of coronary endothelial dysfunction, coronary vasospasm, and adenosine-mediated vasodilatory disorders in patients with ischemia and nonobstructive coronary arteries. Circ. Cardiovasc. Interv. 2022; 15 (8): e012017. DOI: 10.1161/CIRCINTERVENTIONS.122.012017
Gdowski M., Murthy V., Doering M., Monroy-Gonzalez A., Slart R., Brown D.L. Association of isolated coronary microvascular dysfunction with mortality and major adverse cardiac events: a systematic review and meta-analysis of aggregate data. J. Am. Heart Assoc. 2020; 9 (9): e014954. DOI: 10.1161/JAHA.119.014954
Tomanek R. Structure–Function of the Coronary Hierarchy. Coronary Vasculature (Springer US). 2013; 59–81. DOI: 10.1007/978-1-4614-4887-7_4
Chen W., Ni M., Huang H., Cong H., Fu X., Gao W. et al. Chinese expert consensus on the diagnosis and treatment of coronary microvascular diseases (2023 Edition). Med. Comm. 2023; 4 (6): e438. DOI: 10.1002/mco2.438
Булаева Н.И., Голухова Е.З. Эндотелиальная дисфункция и оксидативный стресс: роль в развитии кардиоваскулярной патологии. Креативная кардиология. 2013; 7 (1): 14–22.
Camici P., Tschöpe C., Di Carli M., Rimoldi O., Van Linthout S. Coronary microvascular dysfunction in hypertrophy and heart failure. Cardiovasc. Res. 2020; 116 (4): 806–816. DOI: 10.1093/cvr/cvaa023
Guo Z., Yang Z., Song Z., Li Z., Xiao Y., Zhang Y. et al. Inflammation and coronary microvascular disease: relationship, mechanism and treatment. Front. Cardiovasc. Med. 2024; 11: 1280734. DOI: 10.3389/fcvm.2024.1280734
Godo S., Suda A., Takahashi J., Yasuda S., Shimokawa H. Coronary microvascular dysfunction. Arterioscler. Thromb. Vasc. Biol. 2021; 41(5): 1625–1637. DOI: 10.1161/ATVBAHA.121.316025
Vancheri F., Longo G., Vancheri S., Henein M. Coronary microvascular dysfunction. J. Clin. Med. 2020; 9 (9): 2880. DOI: 10.3390/jcm9092880
Reinstadler S., Stiermaier T., Fuernau G., de Waha S., Desch S., Metzler B. et al. The challenges and impact of microvascular injury in ST- elevation myocardial infarction. Expert Rev. Cardiovasc. Ther. 2016; 14 (4): 431–443. DOI: 10.1586/14779072.2016.1135055
Петросян К.B., Абросимов А.В., Гончарова Е.С. Физиологическая оценка показателей коронарного кровотока в современной стратегии интервенционного лечения ишемической болезни сердца. Грудная и сердечно-сосудистая хирургия. 2024; 66 (3): 270–281. DOI: 10.24022/0236-2791-2024-66-3-270-281
Голухова Е.З., Петросян К.В., Абросимов А.В., Булаева Н.И., Гончарова Е.С., Бердибеков Б.Ш. Влияние оценки фракционного и моментального резерва кровотока на клинические исходы чрескожного коронарного вмешательства: систематический обзор, метаанализ и анализ методом метарегрессии. Российский кардиологический журнал. 2023; 28 (1S): 5325. DOI: 10.15829/1560-4071-2023-5325
Aldiwani H., Mahdai S., Alhatemi G., Bairey Merz C. Microvascular angina: diagnosis and management. Eur/ Cardiol. 2021; 16: e46. DOI: 10.15420/ecr.2021.15
Vrints C., Andreotti F., Koskinas K., Rossello X., Adamo M., Ainslie J. et al. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur. Heart J. 2024; 45 (36): 3415–3537. DOI: 10.1093/eurheartj/ehae177
Ong P., Camici P., Beltrame J., Crea F., Shimokawa H., Sechtem U. et al. International standardization of diagnostic criteria for microvascular angina. Int. J. Cardiol. 2018; 250: 16–20. DOI: 10.1016/j.ijcard.2017.08.068
Schroder J., Michelsen M., Mygind N., Suhrs H., Bove K, Bechsgaard D. et al. Coronary flow velocity reserve predicts adverse prognosis in women with angina and no obstructive coronary artery disease: results from the iPOWER study. Eur. Heart J. 2021; 42 (3): 228–239. DOI: 10.1093/eurheartj/ehaa944
Celermajer D., Sorensen K., Gooch V., Spiegelhalter D., Miller O., Sullivan I. et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992; 340 (8828): 1111–1115. DOI: 10.1016/0140-6736(92)93147-f
Голухова Е.З., Асланиди И.П., Шурупова И.В., Шахова А.А., Румянцева М.Г., Трифонова Т.А., Суркова Н.А. Регионарные показатели перфузии и кровотока миокарда по данным количественной позитронно-эмиссионной томографии как индикаторы многососудистого поражения коронарного русла у больных ишемической болезнью сердца. Грудная и сердечно-сосудистая хирургия. 2023; 65 (2): 161–172. DOI: 10.24022/0236-2791-2023-65-2-161-172
Голухова Е.З., Шурупова И.В., Дорофеев А.В., Рычина И.Е., Трифонова Т.А., Болдырева К.М. Характеристика глобального миокардиального кровотока и коронарного резерва по данным динамической стресс-компьютерной томографии у пациентов с ишемической болезнью сердца. Грудная и сердечно-сосудистая хирургия. 2024; 66 (5): 655–665. DOI: 10.24022/0236-2791-2024-66-5-655-667
Murthy V., Naya M., Taqueti V., Foster C., Gaber M., Haine J. et al. Effects of sex on coronary microvascular dysfunction and cardiac outcomes. Circulation. 2014; 129 (24): 2518–2527. DOI: 10.1161/CIRCULATIONAHA.113.008507
Zhou W., Lee J., Leung S., Lai A., Lee T., Chiang J. et al. Long-term prognosis of patients with coronary microvascular disease using stress perfusion cardiac magnetic resonance. JACC Cardiovasc. Imaging. 2021; 14 (3): 602–611. DOI: 10.1016/j.jcmg.2020.09.034
Thomson L., Wei J., Agarwal M., Haft-Baradaran A., Shufelt C., Mehta P.K. et al. Cardiac magnetic resonance myocardial perfusion reserve index is reduced in women with coronary microvascular dysfunction: A national heart, lung, and blood institute-sponsored study from the women’s ischemia syndrome evaluation. Circ. Cardiovasc. Imaging. 2015; 8 (4): 10.1161/CIRCIMAGING.114.002481 e002481. DOI: 10.1161/CIRCIMAGING.114.002481
Suzuki S., Kaikita K., Yamamoto E., Jinnouchi H., Tsujita K. Role of acetylcholine spasm provocation test as a pathophysiological assessment in nonobstructive coronary artery disease. Cardiovasc. Interv. Ther. 2021; 36 (1): 52–53. DOI: 10.1007/s12928-020-00720-z
Beltrame J., Crea F., Kaski J. C., Ogawa H., Ong P., Sechtem U. et al. International standardization of diagnostic criteria for vasospastic angina. Eur. Heart J. 2017; 38 (33): 2565–2568. DOI: 10.1093/eurheartj/ehv351
Suda A., Takahashi J., Hao K., Kikuchi Y., Shindo T., Ikeda S. et al. Coronary functional abnormalities in patients with angina and nonobstructive coronary artery disease. J. Am. Coll. Cardiol. 2019; 74 (19): 2350–2360. DOI: 10.1016/j.jacc.2019.08.1056
Taqueti V. Coronary microvascular dysfunction in vasospastic angina: provocative role for the microcirculation in macrovessel disease prognosis. J. Am. Coll. Cardiol. 2019; 74 (19): 2361–2364. DOI: 10.1016/j.jacc.2019.09.042
Bairey Merz C., Pepine C., Shimokawa H., Berry C. Treatment of coronary microvascular dysfunction. Cardiovasc. Res. 2020; 116 (4): 856–870. DOI: 10.1093/cvr/cvaa006
Sütsch G., Oechslin E., Mayer I., Hess O.M. Effect of diltiazem on coronary flow reserve in patients with microvascular angina. Int. J. Cardiol. 1995; 52 (2): 135–143. DOI: 10.1016/0167-5273(95)02458-9
Janse T., Konst R., de Vos A., Paradies V., Teerenstra S., van den Oord S. et al. Efficacy of diltiazem to improve coronary vasomotor dysfunction in ANOCA: The EDIT-CMD Randomized Clinical Trial. JACC Cardiovasc. Imaging. 2022; 15 (8): 1473–1484. DOI: 10.1016/j.jcmg.2022.03.012
Ling H., Fu S., Xu M., Wang B., Li B., Li Y. et al. Ranolazine for improving coronary microvascular function in patients with nonobstructive coronary artery disease: a systematic review and meta-analysis with a trial sequential analysis of randomized controlled trials. Quant Imaging Med. Surg. 2024; 14 (2): 1451–1465. DOI: 10.21037/qims-23-1029
Kofler T., Hess S., Moccetti F., Pepine C., Attinger A., Wolfrum M. et al. Efficacy of ranolazine for treatment of coronary microvascular dysfunction – a systematic review and meta-analysis of randomized trials. CJC Open. 2020; 3 (1): 101–108. DOI: 10.1016/j.cjco.2020.09.005
Leonova I., Boldueva S., Zakharova O., Gaykovayam L. Trimetazidine improves symptoms and reduces microvascular dysfunction in patients with microvascular angina. Eur. Heart J. 2017; 38 (1): ehx501.P887. DOI: 10.1093/eurheartj/ehx501.P887
Durante W., Behnammanesh G., Peyton K. Effects of sodium-glucose co-transporter 2 inhibitors on vascular cell function and arterial remodeling. Int. J. Mol. Sci. 2021; 22 (16): 8786. DOI: 10.3390/ijms22168786
Peyton K., Behnammanesh G., Durante G., Durante W. Canagliflozin inhibits human endothelial cell inflammation through the induction of heme oxygenase-1. Int. J. Mol. Sci. 2022; 23 (15): 8777. DOI: 10.3390/ijms23158777
Shin E., Lee J., Yoo S., Park Y., Hong Y., Kim M.H. et al. A randomised, multicentre, double blind, placebo controlled trial to evaluate the efficacy and safety of cilostazol in patients with vasospastic angina. Heart. 2014; 100 (19): 1531–1536. DOI: 10.1136/heartjnl-2014-305986
Ohyama K., Matsumoto Y., Takanami K., Ota H., Nishimiya K., Sugisawa J. et al. Coronary adventitial and perivascular adipose tissue inflammation in patients with vasospastic angina. J. Am. Coll. Cardiol. 2018; 71 (4): 414–425. DOI: 10.1016/j.jacc.2017.11.046
Mohri M., Shimokawa H., Hirakawa Y., Masumoto A., Takeshita A. Rho-kinase inhibition with intracoronary fasudil prevents myocardial ischemia in patients with coronary microvascular spasm. J. Am. Coll. Cardiol. 2003; 41 (1): 15–19. DOI: 10.1016/s0735-1097(02)02632-3
Алиева А.М., Чиркова Н.Н., Пинчук Т.В., Андреева О.Н., Пивоваров В.Ю. Эндотелины и сердечно-сосудистая патология. Российский кардиологический журнал. 2014; 11: 83–87. DOI: 10.15829/1560-4071-2014-11-83-87
Reriani M., Raichlin E., Prasad A., Mathew V., Pumper G., Nelson R. et al. Long-term administration of endothelin receptor antagonist improves coronary endothelial function in patients with early atherosclerosis. Circulation. 2010; 122 (10): 958–966. DOI: 10.1161/CIRCULATIONAHA.110.967406
Ikonomidis I., Lekakis J., Nikolaou M., Paraskevaidis I., Andreadou I., Kaplanoglou T. et al. Inhibition of interleukin-1 by anakinra improves vascular and left ventricular function in patients with rheumatoid arthritis. Circulation. 2008; 117 (20): 2662–2669. DOI: 10.1161/CIRCULATIONAHA.107.731877
Ridker P., Everett B., Thuren T., MacFadyen J., Chang W., Ballantyne C. et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med. 2017; 377 (12): 1119–1131. DOI: 10.1056/NEJMoa1707914
Deussen A., Ohanyan V., Jannasch A., Yin L., Chilian W. Mechanisms of metabolic coronary flow regulation. J. Mol. Cell. Cardiol. 2012; 52 (4): 794–801. DOI: 10.1016/j.yjmcc.2011.10.001
Crea F., Gaspardone A., Araujo L., Da Silva R., Kaski J. C., Davies G., Maseri A. Effects of aminophylline on cardiac function and regional myocardial perfusion: implications regarding its antiischemic action. Am. Heart J. 1994; 127 (4 Pt 1): 817–824. DOI: 10.1016/0002-8703(94)90548-7