Updates in the management of patients with non-obstructive coronary artery disease
DOI:
https://doi.org/10.52692/1857-0011.2024.1-78.16Keywords:
Non-obstructive coronary artery disease, microvascular angina, vasospastic anginaAbstract
A large majority (up to 70%) of patients undergoing coronary angiography because of angina and signs of myocardial ischemia do not have obstructive coronary arteries. The studies carried out in the last decades have shown that microvascular coronary dysfunction (CMD) and epicardial vasospasm are the basic pathophysiological mechanisms of non-obstructive coronary artery disease (CAD), and depending on the underlying mechanism, three clinical endotypes are differentiated: microvascular angina, vasospastic and mixed. Correct diagnosis and endotype-specific treatment of non-obstructive CAD is shown to be associated with a better quality of life and a more favorable long-term prognosis. Patients with non- obstructive CAD require a strict control of their cardiovascular risk factors. Statins and ACE inhibitors have beneficial effects in most patients. First-line anti-anginal treatment are beta-blockers and/or calcium channel blockers, depending on the underlying mechanism (microvascular or vasospastic coronary dysfunction). Second-line drugs are ivabradine, ranolazine, and nicorandil. Rho-kinase inhibitors and endothelin receptor antagonists represent potential drugs for the treatment of these patients in the future.
References
Ballantyne, C.M.; Raichlen, J.S.; Nicholls, S.J.; Erbel, R.; Tardif, J.C.; Brener, S.J.; Cain, V.A.; and Nissen, S.E. Effect of Rosuvastatin Therapy on Coronary Artery Stenoses Assessed by Quantitative Coronary Angiography. Circulation, 117, 19 (2008), 2458–2466.
Beltrame, J.F.; Crea, F.; Kaski, J.C.; Ogawa, H.; Ong, P.; Sechtem, U.; Shimokawa, H.; and Merz, C.N.B. International standardization of diagnostic criteria for vasospastic angina. European Heart Journal, 38, 33 (2017), 2565–2568.
Beltrame, J.F.; Limaye, S.B.; and Horowitz, J.D. The Coronary Slow Flow Phenomenon – A New Coronary Microvascular Disorder. Cardiology, 97, 4 (2002), 197– 202.
Brainin, P.; Frestad, D.; and 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. International Journal of Cardiology, 254, (2018), 1–9.
Cattaneo, M.; Porretta, A.P.; and Gallino, A. Ranolazine: Drug overview and possible role in primary microvascular angina management. International Journal of Cardiology, 181, (2015), 376–381.
Crea, F.; and Lanza, G.A. Treatment of microvascular angina: the need for precision medicine. European heart journal, 37, 19 (2016), 1514–1516.
Erdamar, H.; Sen, N.; Tavil, Y.; Yazici, H.U.; Turfan, M.; Poyraz, F.; Topal, S.; Okuyan, H.; Cemri, M.; and Cengel, A. The effect of nebivolol treatment on oxidative stress and antioxidant status in patients with cardiac syndrome-X. Coronary Artery Disease, 20, 3 (2009), 238–244.
Everaars, H.; de Waard, G.A.; Driessen, R.S.; Danad, I.; van de Ven, P.M.; Raijmakers, P.G.; Lammertsma, A.A.; van Rossum, A.C.; Knaapen, P.; and van Royen, N. Doppler Flow Velocity and Thermodilution to Assess Coronary Flow Reserve: A Head-to-Head Comparison With [15O]H2O PET. JACC: Cardiovascular Interventions, 11, 20 (2018), 2044–2054.
Fearon, W.F.; Balsam, L.B.; Farouque, H.M.O.; Robbins, R.C.; Fitzgerald, P.J.; Yock, P.G.; and Yeung, A.C. Novel Index for Invasively Assessing the Coronary Microcirculation. Circulation, 107, 25 (2003), 3129–3132.
Ford, T.J.; and Berry, C. How to Diagnose and Manage Angina Without Obstructive Coronary Artery Disease: Lessons from the British Heart Foundation CorMicA Trial. Interventional Cardiology Review, 14, 2 (2019), 76.
Ford, T.J.; Stanley, B.; Sidik, N.; Good, R.; Rocchiccioli, P.; McEntegart, M.; Watkins, S.; Eteiba, H.; Shaukat, A.; Lindsay, M.; Robertson, K.; Hood, S.; McGeoch, R.; McDade, R.; et al. 1-Year Outcomes ofAngina Management Guided by Invasive Coronary Function Testing (CorMicA). Cardiovascular Interventions, 13, 1 (2020), 33–45.
Guarini, G.; Huqi, A.; Morrone, D.; Capozza, P.; Todiere, G.; and Marzilli, M. Pharmacological approaches to coronary microvascular dysfunction. Pharmacology & Therapeutics, 144, 3 (2014), 283–302.
Jespersen, L.; Abildstrøm, S.Z.; Hvelplund, A.; and Prescott, E. Persistent angina: Highly prevalent and associated with long-term anxiety, depression, low physical functioning, and quality of life in stable angina pectoris. Clinical Research in Cardiology, 102, 8 (2013), 571–581.
Jespersen, L.; Hvelplund, A.; Abildstrøm, S.Z.; Pedersen, F.; Galatius, S.; Madsen, J.K.; Jørgensen, E.; Kelbæk, H.; and Prescott, E. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. European Heart Journal, 33, 6 (2012), 734–744.
Kaski, J.C.; Crea, F.; Gersh, B.J.; and Camici, P.G. Reappraisal of Ischemic Heart Disease. Circulation, 138, 14 (2018), 1463–1480.
Kikuchi, Y.; Yasuda, S.; Aizawa, K.; Tsuburaya, R.; Ito, Y.; Takeda, M.; Nakayama, M.; Ito, K.; Takahashi, J.; and Shimokawa, H. Enhanced Rho-Kinase Activity in Circulating Neutrophils of Patients With Vasospastic Angina: A Possible Biomarker for Diagnosis and Disease Activity Assessment. Journal of the American College of Cardiology, 58, 12 (2011), 1231–1237.
Knuuti, J.; Wijns, W.; Saraste, A.; Capodanno, D.; Barbato, E.; Funck-Brentano, C.; Prescott, E.; Storey, R.F.; Deaton, C.; Cuisset, T.; Agewall, S.; Dickstein, K.; Edvardsen, T.; Escaned, J.; et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes: The Task Force for the diagnosis and management of chronic coronary syndromes of the European Society of Cardiology (ESC). European Heart Journal, 41, 3 (2020), 407–477.
Kunadian, V.; Chieffo, A.; Camici, P.G.; Berry, C.; Escaned, J.; Maas, A.H.E.M.; Prescott, E.; Karam, N.; Appelman, Y.; Fraccaro, C.; Buchanan, G.L.; Manzo-Silberman, S.; Al-Lamee, R.; Regar, E.; et al. 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. EuroIntervention, 16, 13 (2021), 1049–1069.
Matsuda, Y.; Akita, H.; Terashima, M.; Shiga, N.; Kanazawa, K.; and Yokoyama, M. Carvedilol improves endothelium-dependent dilatation in patients with coronary artery disease. American Heart Journal, 140, 5 (2000), 753–759.
Mejía-Rentería, H.; van der Hoeven, N.; van de Hoef, T.P.; Heemelaar, J.; Ryan, N.; Lerman, A.; van Royen, N.; and Escaned, J. Targeting the dominant mechanism of coronary microvascular dysfunction with intracoronary physiology tests. The International Journal of Cardiovascular Imaging 2017 33:7, 33, 7 (2017), 1041–1059.
Merz, C.N.B.; Pepine, C.J.; Walsh, M.N.; Fleg, J.L.; Camici, P.G.; Chilian, W.M.; Clayton, J.A.; Cooper, L.S.; Crea, F.; Carli, M. Di; Douglas, P.S.; Galis, Z.S.; Gurbel, P.; Handberg, E.M.; et al. Ischemia and No Obstructive Coronary Artery Disease (INOCA). Circulation, 135, 11 (2017), 1075–1092.
Min, J.K.; Dunning, A.; Lin, F.Y.; Achenbach, S.; Al-Mallah, M.; Budoff, M.J.; Cademartiri, F.; Callister, T.Q.; Chang, H.J.; Cheng, V.; Chinnaiyan, K.; Chow, B.J.W.; Delago, A.; Hadamitzky, M.; 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. Journal of the American College of Cardiology, 58, 8 (2011), 849–860.
Mohri, M.; Shimokawa, H.; Hirakawa, Y.; Masumoto, A.; and Takeshita, A. Rho-kinase inhibition with intracoronary fasudil prevents myocardial ischemia in patients with coronary microvascular spasm. Journal of the American College of Cardiology, 41, 1 (2003), 15–19.
Murai, T.; Yonetsu, T.; Kanaji, Y.; Usui, E.; Hoshino, M.; Hada, M.; Hamaya, R.; Kanno, Y.; Lee, T.; and Kakuta, T. Prognostic value of the index of microcirculatory resistance after percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndrome. Catheterization and Cardiovascular Interventions, 92, 6 (2018), 1063–1074.
Neumann, F.J.; Sechtem, U.; Banning, A.P.; Bonaros, N.; Bueno, H.; Bugiardini, R.; Chieffo, A.; Crea, F.; Czerny, M.; Delgado, V.; Dendale, P.; Knuuti, J.; Wijns, W.; Flachskampf, F.A.; et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromesThe Task Force for the diagnosis and management of chronic coronary syndromes of the European Society of Cardiology (ESC). European Heart Journal, 41, 3 (2020), 407–477.
Nihei, T.; Takahashi, J.; Hao, K.; Kikuchi, Y.; Odaka, Y.; Tsuburaya, R.; Nishimiya, K.; Matsumoto, Y.; Ito, K.; Miyata, S.; Sakata, Y.; and Shimokawa, H. Prognostic impacts of Rho-kinase activity in circulating leucocytes in patients with vasospastic angina. European Heart Journal, 39, 11 (2018), 952–959.
Nobuyoshi, M.; Abe, M.; Nosaka, H.; Kimura, T.; Yokoi, H.; Hamasaki, N.; Shindo, T.; Kimura, K.; Nakamura, T.; Nakagawa, Y.; Shiode, N.; Sakamoto, A.; Kakura, H.; Iwasaki, Y.; et al. Statistical analysis of clinical risk factors for coronary artery spasm: Identification of the most important determinant. American Heart Journal, 124, 1 (1992), 32–38.
Noel Bairey Merz, C.; Handberg, E.M.; Shufelt, C.L.; Mehta, P.K.; Minissian, M.B.; Wei, J.; Thomson, L.E.J.; Berman, D.S.; Shaw, L.J.; Petersen, J.W.; Brown, G.H.; David Anderson, R.; Shuster, J.J.; Cook-Wiens, G.; et al. A randomized, placebo-controlled trial of late Na current inhibition (ranolazine) in coronary microvascular dysfunction (CMD): impact on angina and myocardial perfusion reserve. European Heart Journal, 37, (2016), 1504–1513.
Ong, P.; Athanasiadis, A.; and Sechtem, U. Pharmacotherapy for coronary microvascular dysfunction. European Heart Journal - Cardiovascular Pharmacotherapy, 1, 1 (2015), 65–71.
Ong, P.; Athanasiadis, A.; and Sechtem, U. Pharmacotherapy for coronary microvascular dysfunction. European Heart Journal - Cardiovascular Pharmacotherapy, 1, 1 (2015), 65–71.
Ong, P.; Camici, P.G.; Beltrame, J.F.; Crea, F.; Shimokawa, H.; Sechtem, U.; Kaski, J.C.; and Bairey Merz, C.N. International standardization of diagnostic criteria for microvascular angina. International Journal of Cardiology, 250, (2018), 16–20.
Panting, J.R.; Gatehouse, P.D.; Yang, G.-Z.; Grothues, F.; Firmin, D.N.; Collins, P.; and Pennell, D.J. Abnormal Subendocardial Perfusion in Cardiac Syndrome X Detected by Cardiovascular Magnetic Resonance Imaging. New England Journal of Medicine, 346, 25 (2002), 1948–1953.
Patel, M.R.; Peterson, E.D.; Dai, D.; Brennan, J.M.; Redberg, R.F.; Anderson, H.V.; Brindis, R.G.; and Douglas, P.S. 1056/NEJMoa0907272) was updated on. N Engl J Med, 362, 10 (2010), 886–95.
Patel, M.R.; Peterson, E.D.; Dai, D.; Brennan, J.M.; Redberg, R.F.; Anderson, H.V.; Brindis, R.G.; and Douglas, P.S. Low Diagnostic Yield of Elective Coronary Angiography. https://doi.org/10.1056/NEJMoa0907272, 362, 10 (2010), 886–895.
Pauly, D.F.; Johnson, B.D.; Anderson, R.D.; Handberg, E.M.; Smith, K.M.; Cooper-Dehoff, R.M.; Sopko, G.; Sharaf, B.M.; Kelsey, S.F.; Merz, C.N.B.; and Pepine, C.J. In women with symptoms of cardiac ischemia, nonobstructive coronary arteries, and microvascular dysfunction, angiotensin-converting enzyme inhibition is associated with improved microvascular function: A double-blind randomized study from the National Heart, Lung and Blood Institute Women’s Ischemia Syndrome Evaluation (WISE). American Heart Journal, 162, 4 (2011), 678–684.
Pepine, C.J.; Anderson, R.D.; Sharaf, B.L.; Reis, S.E.; Smith, K.M.; Handberg, E.M.; Johnson, B.D.; Sopko, G.; and Bairey Merz, C.N. 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. Journal of the American College of Cardiology, 55, 25 (2010), 2825–2832.
Pijls, N.H.J.; De Bruyne, B.; Smith, L.; Aarnoudse, W.; Barbato, E.; Bartunek, J.; Bech, G.J.W.; and Van De Vosse, F. Coronary Thermodilution to Assess Flow Reserve. Circulation, 105, 21 (2002), 2482–2486.
Pijls, N.H.J.; Klauss, V.; Siebert, U.; Powers, E.; Takazawa, K.; Fearon, W.F.; Escaned, J.; Tsurumi, Y.; Akasaka, T.; Samady, H.; and De Bruyne, B. Coronary Pressure Measurement After Stenting Predicts Adverse Events at Follow-Up. Circulation, 105, 25 (2002), 2950– 2954.
Radico, F.; Cicchitti, V.; Zimarino, M.; and De Caterina, R. Angina Pectoris and Myocardial Ischemia in the Absence of Obstructive Coronary Artery Disease: Practical Considerations for Diagnostic Tests. JACC: Cardiovascular Interventions, 7, 5 (2014), 453–463.
Rahman, H.; Corcoran, D.; Aetesam-Ur-Rahman, M.; Hoole, S.P.; Berry, C.; and Perera, D. Diagnosis of patients with angina and non-obstructive coronary disease in the catheter laboratory. Heart, 105, 20 (2019), 1536–1542.
Reriani, M.; Raichlin, E.; Prasad, A.; Mathew, V.; Pumper, G.M.; Nelson, R.E.; Lennon, R.; Rihal, C.; Lerman, L.O.; and Lerman, A. Long-term administration of endothelin receptor antagonist improves coronary endothelial function in patients with early atherosclerosis. Circulation, 122, 10 (2010), 958–966.
Ridker, P.M.; MacFadyen, J.; Libby, P.; and Glynn, R.J. Relation of Baseline High-Sensitivity C-Reactive Protein Level to Cardiovascular Outcomes With Rosuvastatin in the Justification for Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER). The American Journal of Cardiology, 106, 2 (2010), 204–209.
Robertson, R.M.; Wood, A.J.J.; Vaughn, W.K.; and Robertson, D. Exacerbation of vasotonic angina pectoris by propranolol. Circulation, 65, 2 (1982), 281–285.
Russo, G.; Di Franco, A.; Lamendola, P.; Tarzia, P.; Nerla, R.; Stazi, A.; Villano, A.; Sestito, A.; Lanza, G.A.; and Crea, F. Lack of effect of nitrates on exercise stress test results in patients with microvascular angina. Cardiovascular Drugs and Therapy, 27, 3 (2013), 229– 234.
Sara, J.D.; Widmer, R.J.; Matsuzawa, Y.; Lennon, R.J.; Lerman, L.O.; and Lerman, A. Prevalence of Coronary Microvascular Dysfunction Among Patients With Chest Pain and Nonobstructive Coronary Artery Disease. (2015).
Shimokawa, H.; Sunamura, S.; and Satoh, K. RhoA/ Rho-Kinase in the Cardiovascular System. Circulation Research, 118, 2 (2016), 352–366.
Skalidis, E.I.; Hamilos, M.I.; Chlouverakis, G.; Zacharis, E.A.; and Vardas, P.E. Ivabradine improves coronary flow reserve in patients with stable coronary artery disease. Atherosclerosis, 215, 1 (2011), 160–165.
Suda, A.; Takahashi, J.; Hao, K.; Kikuchi, Y.; Shindo, T.; Ikeda, S.; Sato, K.; Sugisawa, J.; Matsumoto, Y.; Miyata, S.; Sakata, Y.; and Shimokawa, H. Coronary Functional Abnormalities in Patients With Angina and Nonobstructive Coronary Artery Disease. Journal of the American College of Cardiology, 74, 19 (2019), 2350– 2360.
Sugano, Y.; Anzai, T.; Yagi, T.; and Noma, S. Impact of high-density lipoprotein cholesterol level in patients with variant angina pectoris. International Journal of Cardiology, 140, 2 (2010), 175–181.
Timmis, A.; Townsend, N.; Gale, C.P.; Torbica, A.; Lettino, M.; Petersen, S.E.; Mossialos, E.A.; Maggioni, A.P.; Kazakiewicz, D.; May, H.T.; De Smedt, D.; Flather, M.; Zuhlke, L.; Beltrame, J.F.; et al. European society of cardiology: Cardiovascular disease statistics 2019. European Heart Journal, 41, 1 (2020), 12–85.
Villano, A.; Di Franco, A.; Nerla, R.; Sestito, A.; Tarzia, P.; Lamendola, P.; Di Monaco, A.; Sarullo, F.M.; Lanza, G.A.; and Crea, F. Effects of Ivabradine and Ranolazine in Patients With Microvascular Angina Pectoris. The American Journal of Cardiology, 112, 1 (2013), 8–13.
Virani, S.S.; Newby, L.K.; Arnold, S. V.; Bittner, V.; Brewer, L.P.C.; Demeter, S.H.; Dixon, D.L.; Fearon, W.F.; Hess, B.; Johnson, H.M.; Kazi, D.S.; Kolte, D.; Kumbhani, D.J.; LoFaso, J.; et al. 2023 AHA/ACC/ACCP/ASPC/ NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Journal of the American College of Cardiology, 82, 9 (2023), 833–955.
Wessel, T.R.; Arant, C.B.; McGorray, S.P.; Sharaf, B.L.; Reis, S.E.; Kerensky, R.A.; Von Mering, G.O.; Smith, K.M.; Pauly, D.F.; Handberg, E.M.; Mankad, S.; Olson, M.B.; Johnson, B.D.; Merz, C.N.B.; et al. Coronary microvascular reactivity is only partially predicted by atherosclerosis risk factors or coronary artery disease in women evaluated for suspected ischemia: Results from the NHLBI Women’s Ischemia Syndrome Evaluation (WISE). Clinical Cardiology, 30, 2 (2007), 69–74.
Widmer, R.J.; Samuels, B.; Samady, H.; Price, M.J.; Jeremias, A.; Anderson, R.D.; Jaffer, F.A.; Escaned, J.; Davies, J.; Prasad, M.; Grines, C.; and Lerman, A. The functional assessment of patients with non-obstructive coronary artery disease: expert review from an international microcirculation working group. EuroIntervention, 14, 16 (2019), 1694–1702.
Williams, B.; Mancia, G.; Spiering, W.; Rosei, E.A.; Azizi, M.; Burnier, M.; Clement, D.L.; Coca, A.; de Simone, G.; Dominiczak, A.F.; Kahan, T.; Mahfoud, F.; Redon, J.; Ruilope, L.M.; et al. 2018 ESC/ESH Guidelines for the Management of Arterial Hypertension : The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension*. Manual of Hypertension of the European Society of Hypertension, (2019), 543–627.
Zhang, X.; Li, Q.; Zhao, J.; Li, X.; Sun, X.; Yang, H.; Wu, Z.; and Yang, J. Effects of combination of statin and calcium channel blocker in patients with cardiac syndrome X. Coronary Artery Disease, 25, 1 (2014), 40–44.
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