Інвазивна діагностика INOCA/АNOCA, коронарний атеросклероз і вазоспастична стенокардія як поєднані причини ішемії міокарда, їх сучасна інвазивна діагностика та лікування
##plugins.themes.bootstrap3.article.sidebar##
TЦя робота ліцензується відповідно до ліцензії Creative Commons Attribution-ShareAlike 4.0 International License.
##plugins.themes.bootstrap3.article.main##
https://orcid.org/0000-0002-8133-9318
Анотація
Мета роботи – оцінити безпечність та ефективність застосування інвазивної провокаційної проби з ацетилхоліном для ендотипування пацієнтів із INOCA/ANOCA та визначити механізми ішемії при поєднанні функціональних розладів із коронарним атеросклерозом, а також розробити персоніфіковані підходи до лікування.
Матеріали і методи. У дослідження залучено 61 пацієнта (досліджувана група А (n=42) та контрольна група Б (n=19)) із симптомами стенокардії та об'єктивними ознаками ішемії міокарда на ЕКГ (насамперед, депресія або елевація сегмента ST під час тесту з дозованим фізичним навантаженням) і за даними проведеної коронарної ангіографії. Сформовані групи є статистично порівнянними за демографічними показниками та факторами серцево-судинного ризику. Не виявлено значущої різниці між групами за віком (p=0,57), статтю (p=0,76), наявністю артеріальної гіпертензії (p=0,68), цукрового діабету (p>0,99) та дисліпідемії (p=0,37). Протокол проведення провокаційної проби передбачав ступінчасте внутрішньокоронарне введення ацетилхоліну під моніторуванням ЕКГ та коронароангіографії.
Результати та обговорення. Переважно механізмом виникнення ішемії без обструкції коронарних артерій (INOCA) є епікардіальний вазоспазм, його було діагностовано у 59,5 % випадків. Ендотеліальна дисфункція виявлена у 26,2 % пацієнтів, а ізольований мікроваскулярний спазм – у 14,3 %. Найчастіше маркером ішемії на ЕКГ була інверсія зубця Т (59,5 %). Доведено високу безпечність методу: небезпечних для життя аритмій (шлуночкова тахікардія/фібриляція шлуночків) не зафіксовано. Виявлені ускладнення (атріовентрикулярні блокади II–III ступенів у 28,6 % пацієнтів досліджуваної групи) мали виключно транзиторний характер. Особливу увагу приділено феномену «подвійного удару» – поєднанню атеросклерозу й вазоспазму, що суттєво обтяжує прогноз пацієнтів.
Висновки. Провокаційна проба з ацетилхоліном дає змогу точно ендотипувати пацієнтів з INOCA та персоніфікувати терапію: призначення блокаторів кальцієвих каналів при вазоспазмі та обов’язкову відміну неселективних бета-блокаторів, що запобігає небажаній вазоконстрикції.
##plugins.themes.bootstrap3.article.details##
Ключові слова:
Посилання
Lindstrom M, DeCleene N, Dorsey H, Fuster V, Johnson CO, LeGrand KE, Mensah GA, Razo C, Stark B, Varieur Turco J, Roth GA. Global Burden of Cardiovascular Diseases and Risks Collaboration, 1990-2021. J Am Coll Cardiol. 2022 Dec 20;80(25):2372-425. https://doi.org/10.1016/j.jacc.2022.11.001
Kunadian V, Chieffo A, Camici PG, Berry C, Escaned J, Maas AHEM, Prescott E, Karam N, Appelman Y, Fraccaro C, Buchanan GL, Manzo-Silberman S, Al-Lamee R, Regar E, Lansky A, Abbott JD, Badimon L, Duncker DJ, Mehran R, Capodanno D, Baumbach A. An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology & Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group. EuroIntervention. 2021;16:1049-69. https://doi.org/10.4244/EIJY20M07_01
Ciccarelli G, Barbato E, Toth GG, et al. Angiography versus hemodynamics to predict the natural history of coronary stenoses: fractional flow reserve versus angiography in multivessel evaluation 2 substudy. Circulation. 2018;137:1475-85. https://doi.org/10.1161/CIRCULATIONAHA.117.028782
Curzen N, Rana O, Nicholas Z, et al. Does routine pressure wire assessment influence management strategy at coronary angiography for diagnosis of chest pain: the RIPCORD study. Circ Cardiovasc Interv. 2014;7:248-55. https://doi.org/10.1161/CIRCINTERVENTIONS.113.000978
Fearon WF, Nishi T, De Bruyne B, et al. Clinical outcomes and cost-effectiveness of fractional flow reserve-guided percutaneous coronary intervention in patients with stable coronary artery disease: three-year follow-up of the FAME 2 trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation). Circulation. 2018;137:480-7. https://doi.org/10.1161/CIRCULATIONAHA.117.031907
Vrints C, Andreotti F, Koskinas KC, Rossello X, Adamo M, Ainslie J, Banning AP, Budaj A, Buechel RR, Chiariello GA, Chieffo A, Christodorescu RM, Deaton C, Doenst T, Jones HW, Kunadian V, Mehilli J, Milojevic M, Piek JJ, Pugliese F, Rubboli A, Semb AG, Senior R, Ten Berg JM, Van Belle E, Van Craenenbroeck EM, Vidal-Perez R, Winther S; ESC Scientific Document Group. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J. 2024 Sep 29;45(36):3415-537. https://doi.org/10.1093/eu7.
Khuddus MA, Pepine CJ, Handberg EM, et al. An intravascular ultrasound analysis in women experiencing chest pain in the absence of obstructive coronary artery disease: a substudy from the National Heart, Lung and Blood Institute-Sponsored Women’s Ischemia Syndrome Evaluation (WISE). J Interv Cardiol. 2010;23:511-19. https://doi.org/10.1111/j.1540-8183.2010.00598.x
Ong P, Camici PG, Beltrame JF, Crea F, et al. International standardization of diagnostic criteria for micro-vascular angina. Int J Cardiol. 2018;250:16-20. https://doi.org/10.1016/j.ijcard.2017.08.068
Mejia-Renteria H, van der Hoeven N, van de Hoef TP, et al. Targeting the dominant mechanism of coronary microvascular dysfunction with intracoronary physiology tests. Int J Cardiovasc Imaging. 2017;33:1041-59. https://doi.org/10.1007/s10554-017-1136-9
Prinzmetal M, Kennamer R, Merliss R, et al. Angina pectoris. A variant form of angina pectoris; preliminary report. Am J Med. 1959;27:375-88. https://doi.org/10.1016/0002-9343(59)90003-8
Beltrame JF, Crea F, Kaski JC, et al. Coronary Vasomotion Disorders International Study Group (COVADIS). International standardization of diagnostic criteria for vasospastic angina. Eur Heart J. 2015;38:2565-8. https://doi.org/10.1093/eurheartj/ehv351
Suda A, Takahashi J, Hao K, et al. Coronary functional abnormalities in patients with angina and nonobstructive coronary artery disease. J Am Coll Cardiol. 2019;74:2350-60. https://doi.org/10.1016/j.jacc.2019.08.1056
Reeh J, Therming CB, Heitmann M, et al. Prediction of obstructive coronary artery disease and prognosis in patients with suspected stable angina. Eur Heart J. 2019;40:1426-35. https://doi.org/10.1093/eurheartj/ehy806
Douglas PS, Hoffmann U, Patel MR, Mark DB, Al-Khalidi HR, Cavanaugh B, et al. Outcomes of anatomical versus functional testing for coronary artery disease. N Engl J Med. 2015;372(14):1291-300. https://doi.org/10.1056/NEJMoa1415516
Pepine CJ, Anderson RD, Sharaf BL, et al. Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia results from the National Heart, Lung and Blood Institute WISE (Women’s Ischemia Syndrome Evaluation) study. J Am Coll Cardiol. 2010;55:2825-32. https://doi.org/10.1016/j.jacc.2010.01.054
Jespersen L, Hvelplund A, Abildstrom SZ, et al. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J. 2012;33:734-44. https://doi.org/10.1093/eurheartj/ehr331
Murthy VL, Naya M, Taqueti VR, et al. Effects of sex on coronary microvascular dysfunction and cardiac outcomes. Circulation. 2014;129:2518-27. https://doi.org/10.1161/CIRCULATIONAHA.113.008507
Sara JD, Widmer RJ, Matsuzawa Y, et al. Prevalence of coronary microvascular dysfunction among patients with chest pain and nonobstructive coronary artery disease. JACC Cardiovasc Interv. 2015;8:1445-53. https://doi.org/10.1016/j.jcin.2015.06.017
Zeiher AM, Schachinger V, Minners J. Long-term cigarette smoking impairs endothelium-dependent coronary arterial vasodilator function. Circulation. 1995;92:1094-100. https://doi.org/10.1161/01.cir.92.5.1094
Mygind ND, Michelsen MM, Pena A, et al. Coronary microvascular function and cardiovascular risk factors in women with angina pectoris and no obstructive coronary artery disease: the iPOWER study. J Am Heart Assoc. 2016;5:e003064. https://doi.org/10.1161/JAHA.115.003064
Chhabra L, Kowlgi NG. Low incidence of diabetes mellitus in coronary micro-vascular dysfunction: an intriguing association. JACC Cardiovasc Interv. 2016;9:395-6. https://doi.org/10.1016/j.jcin.2015.11.017
Schroder J, Mygind ND, Frestad D, et al. Pro-inflammatory biomarkers in women with non-obstructive angina pectoris and coronary microvascular dysfunction. Int J Cardiol Heart Vasc. 2019;24:100370. https://doi.org/10.1016/j.ijcha.2019.100370
Quarta R, Martino G, Romano LR, et al. The Role of Circulating Biomarkers in Patients with Coronary Microvascular Disease. Biomolecules. 2025;15(2):177. https://doi.org/10.3390/biom15020177
Recio-Mayoral A, Rimoldi OE, Camici PG, et al. Inflammation and microvascular dysfunction in cardiac syndrome X patients without conventional risk factors for coronary artery disease. JACC Cardiovasc Imaging. 2013;6:660-7. https://doi.org/10.1016/j.jcmg.2012.12.011
Ishimori ML, Martin R, Berman DS, et al. Myocardial ischemia in the absence of obstructive coronary artery disease in systemic lupus erythematosus. JACC Cardiovasc Imaging. 2011;4:27-33. https://doi.org/10.1016/j.jcmg.2010.09.019
Recio-Mayoral A, Mason JC, Kaski JC, et al. Chronic inflammation and coronary microvascular dysfunction in patients without risk factors for coronary artery disease. Eur Heart J. 2009;30:1837-43. https://doi.org/10.1093/eurheartj/ehp205
Fairweather D. Sex differences in inflammation during atherosclerosis. Clin Med Insights Cardiol. 2014;8s3:49-59. https://doi.org/10.4137/CMC.S17068
Beltrame JF, Sasayama S, Maseri A. Racial heterogeneity in coronary artery vasomotor reactivity: differences between Japanese and Caucasian patients. J Am Coll Cardiol. 1999;33:1442-52. https://doi.org/10.1016/s0735-1097(99)00073-x
Sueda S, Kohno H, Fukuda H, et al. Frequency of provoked coronary spasms in patients undergoing coronary arteriography using a spasm provocation test via intracoronary administration of ergonovine. Angiology. 2004;55:403-11. https://doi.org/10.1177/000331970405500407
Hung MY, Hsu KH, Hung MJ, et al. Interactions among gender, age, hypertension and C-reactive protein in coronary vasospasm. Eur J Clin Invest. 2010;40:1094-103. https://doi.org/10.1111/j.1365-2362.2010.02360.x
Bertrand ME, LaBlanche JM, Tilmant PY, et al. Frequency of provoked coronary arterial spasm in 1089 consecutive patients undergoing coronary arteriography. Circulation. 1982;65:1299-306. https://doi.org/10.1161/01.cir.65.7.1299
Hung MJ, Cherng WJ, Cheng CW, et al. Comparison of serum levels of inflammatory markers in patients with coronary vasospasm without significant fixed coronary artery disease versus patients with stable angina pectoris and acute coronary syndromes with significant fixed coronary artery disease. Am J Cardiol. 2006;97:1429-34. https://doi.org/10.1016/j.amjcard.2005.12.035
Hung MJ, Cheng CW, Yang NI, et al. Coronary vasospasm-induced acute coronary syndrome complicated by life-threatening cardiac arrhythmias in patients without hemodynamically significant coronary artery disease. Int J Cardiol. 2007;117:37-44.https://doi.org/10.1016/j.ijcard.2006.03.055
Aziz A, Hansen HS, Sechtem U, et al. Sex-related differences in vasomotor function in patients with angina and unobstructed coronary arteries. J Am Coll Cardiol. 2017;70:2349-58. https://doi.org/10.1016/j.jacc.2017.09.016
Ong P, Athanasiadis A, Borgulya G, et al. 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. 2012;59:655-62. https://doi.org/10.1016/j.jacc.2011.11.015
Sato K, Kaikita K, Nakayama N, et al. Coronary vasomotor response to intracoronary acetylcholine injection, clinical features, and long-term prognosis in 873 consecutive patients with coronary spasm: analysis of a single-center study over 20 years. J Am Heart Assoc. 2013;2:e000227. https://doi.org/10.1161/JAHA.113.000227
Nobuyoshi M, Abe M, Nosaka H, et al. Statistical analysis of clinical risk factors for coronary artery spasm: identification of the most important determinant. Am Heart J. 1992;124:32-8. https://doi.org/10.1016/0002-8703(92)90917-k
Camici PG, d’Amati G, Rimoldi O. Coronary microvascular dysfunction: mechanisms and functional assessment. Nat Rev Cardiol. 2015;12(1):48-62. https://doi.org/10.1038/nrcardio.2014.160
Escaned J, Flores A, García-Pavía P, et al. Assessment of microcirculatory remodeling with intracoronary flow velocity and pressure measurements: validation with endomyocardial sampling in cardiac allografts. Circulation. 2009;120:1561-8. https://doi.org/10.1161/CIRCULATIONAHA.108.834739
Pries AR, Badimon L, Bugiardini R, et al. Coronary vascular regulation, remodelling, and collateralization: mechanisms and clinical implications on behalf of the working group on coronary pathophysiology and microcirculation. Eur Heart J. 2015;36:3134-46. https://doi.org/10.1093/eurheartj/ehv100
Sorop O, Merkus D, de Beer VJ, et al. Functional and structural adaptations of coronary microvessels distal to a chronic coronary artery stenosis. Circ Res. 2008;102:795-803. https://doi.org/10.1161/CIRCRESAHA.108.172528
Sorop O, van den Heuvel M, van Ditzhuijzen NS, et al. Coronary microvascular dysfunction after long-term diabetes and hypercholesterolemia. Am J Physiol Heart Circ Physiol. 2016;311:H1339-51. https://doi.org/10.1152/ajpheart.00458.2015
Morise AP, Beto R. The specificity of exercise electrocardiography in women grouped by estrogen status. Int J Cardiol. 1997;60:55-65. https://doi.org/10.1016/s0167-5273(97)02953-7
Beltrame JF, Crea F, Kaski JC, et al. Coronary Vasomotion Disorders International Study Group (COVADIS). International standardization of diagnostic criteria for vasospastic angina. Eur Heart J. 2017;38:2565-8. https://doi.org/10.1093/eurheartj/ehv351
Jespersen L, Abildstrom SZ, Hvelplund A, et al. Persistent angina: highly prevalent and associated with long-term anxiety, depression, low physical functioning, and quality of life in stable angina pectoris. Clin Res Cardiol. 2013;102:571-81. https://doi.org/10.1007/s00392-013-0568-z
Brainin P, Frestad D, Prescott E. The prognostic value of coronary endothelial and microvascular dysfunction in subjects with normal or non-obstructive coronary artery disease: a systematic review and meta-analysis. Int J Cardiol. 2018;254:1-9.https://doi.org/10.1016/j.ijcard.2017.10.052
Shaw LJ, Merz CN, Pepine CJ, et al. The economic burden of angina in women with suspected ischemic heart disease: results from the National Institutes of Health-National Heart, Lung, and Blood Institute-sponsored Women’s Ischemia Syndrome Evaluation. Circulation. 2006;114:894-904. https://doi.org/10.1161/CIRCULATIONAHA.105.609990
Jespersen L, Abildstrom SZ, Hvelplund A, et al. Burden of hospital admission and repeat angiography in angina pectoris patients with and without coronary artery disease: a registry-based cohort study. PLoS One. 2014;9:e93170. https://doi.org/10.1371/journal.pone.0093170
Shaw LJ, Shaw RE, Merz CN, et al. Impact of ethnicity and gender differences on angiographic coronary artery disease prevalence and in-hospital mortality in the American College of Cardiology-National Cardiovascular Data Registry. Circulation. 2008;117:1787-801. https://doi.org/10.1161/CIRCULATIONAHA.107.726562
Min JK, Dunning A, Lin FY, et al. Age-and sex-related differences in all-cause mortality risk based on coronary computed tomography angiography findings results from the International Multicenter CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: an International Multicenter Registry) of 23,854 patients without known coronary artery disease. J Am Coll Cardiol. 2011;58:849-60. https://doi.org/10.1016/j.jacc.2011.02.074
Gulati M, Cooper-DeHoff RM, McClure C et al. Adverse cardiovascular outcomes in women with nonobstructive coronary artery disease: a report from the Women’s Ischemia Syndrome Evaluation Study and the St James Women Take Heart Project. Arch Intern Med. 2009;169:843-50. https://doi.org/10.1001/archinternmed.2009.50
Bairey Merz CN, Shaw LJ, Reis SE, Bittner V, Kelsey SF, et al. Insights from the NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation (WISE) study: part II: gender differences in presentation, diagnosis, and outcome with regard to gender-based pathophysiology of atherosclerosis and macrovascular and microvascular coronary disease. J Am Coll Cardiol. 2006;47:S21-9. https://doi.org/10.1016/j.jacc.2004.12.084
Radico F, Zimarino M, Fulgenzi F, et al. Determinants of long-term clinical outcomes in patients with angina but without obstructive coronary artery disease: a systematic review and meta-analysis. Eur Heart J. 2018;39:2135-46. https://doi.org/10.1093/eurheartj/ehy185
Igarashi Y, Tamura Y, Tanabe Y, et al. Angina-linked syncope and lack of calcium antagonist therapy predict cardiac arrest before definitive diagnosis of vasospastic angina. Coron Artery Dis. 1994;5:881-7. https://pubmed.ncbi.nlm.nih.gov/7719520/
Igarashi Y, Tamura Y, Suzuki K, et al. Coronary artery spasm is a major cause of sudden cardiac arrest in survivors without underlying heart disease. Coron Artery Dis. 1993;4:177-85. https://doi.org/10.1097/00019501-199302000-00008
Lanza GA, Sestito A, Sgueglia GA, et al. Current clinical features, diagnostic assessment and prognostic determinants of patients with variant angina. Int J Cardiol. 2007;118:41-7. https://doi.org/10.1016/j.ijcard.2006.06.016
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. Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina: CorMicA Trial. J Am Coll Cardiol. 2018 Dec 11;72(23 Pt A):2841-55. https://doi.org/10.1016/j.jacc.2018.09.006
Ford TJ, Corcoran D, Berry C. Stable coronary syndromes: pathophysiology, diagnostic advances and therapeutic need. Heart. 2018;104:284-92. https://doi.org/10.1136/heartjnl-2017-311446