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Treatment of Angina Pectoris Associated with Coronary Microvascular Dysfunction

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Abstract

Treatment of angina pectoris associated with coronary microvascular dysfunction is challenging as the underlying mechanisms are often diverse and overlapping. Patients with type 1 coronary microvascular dysfunction (i.e. absence of epicardial coronary artery disease and myocardial disease) should receive strict control of their cardiovascular risk factors and thus receive statins and ACE-inhibitors in most cases. Antianginal medication consists of ß-blockers and/or calcium channel blockers. Second line drugs are ranolazine and nicorandil with limited evidence. Despite individually titrated combinations of these drugs up to 30 % of patients have refractory angina. Rho-kinase inhibitors and endothelin-receptor antagonists represent potential drugs that may prove useful in these patients in the future.

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References

  1. Camici PG, Crea F. Coronary microvascular dysfunction. N Engl J Med. 2007;356:830–40.

    Article  CAS  PubMed  Google Scholar 

  2. Lanza GA, Camici PG, Galiuto L, Niccoli G, Pizzi C, di Monaco a, Sestito a, novo S, Piscione F, Tritto I, Ambrosio G, Bugiardini R, Crea F, Marzilli M, Gruppo di studio di Fisiopatologia Coronarica e Microcircolazione, Società Italiana di Cardiologia. Methods to investigate coronary microvascular function in clinical practice. J Cardiovasc Med (Hagerstown). 2013;14:1–18.

    Article  Google Scholar 

  3. Lamendola P, Lanza GA, Spinelli A, Sgueglia GA, Di Monaco A, Barone L, Sestito A, Crea F. Long-term prognosis of patients with cardiac syndrome X. Int J Cardiol. 2010;140:197–9.

    Article  PubMed  Google Scholar 

  4. Reis SE, Holubkov R, Conrad smith AJ, Kelsey SF, Sharaf BL, Reichek N, Rogers WJ, Merz CN, Sopko G, Pepine CJ. WISE investigators. Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: results from the NHLBI WISE study. Am Heart J. 2001;141:735–41.

    Article  CAS  PubMed  Google Scholar 

  5. Ong P, Athanasiadis A, Borgulya G, Mahrholdt H, Kaski JC, Sechtem U. 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.

    Article  CAS  PubMed  Google Scholar 

  6. Pasceri V, Lanza GA, Buffon A, Montenero AS, Crea F, Maseri A. Role of abnormal pain sensitivity and behavioral factors in determining chest pain in syndrome X. J Am Coll Cardiol. 1998;31:62–6.

    Article  CAS  PubMed  Google Scholar 

  7. Lanza GA, Giordano A, Pristipino C, Calcagni ML, Meduri G, Trani C, Franceschini R, Crea F, Troncone L, Maseri A. Abnormal cardiac adrenergic nerve function in patients with syndrome X detected by [123I]metaiodobenzylguanidine myocardial scintigraphy. Circulation. 1997;96:821–6.

    Article  CAS  PubMed  Google Scholar 

  8. Granger DN, Rodrigues SF, Yildirim A, Senchenkova EY. Microvascular responses to cardiovascular risk factors. Microcirculation. 2010;17:192–205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Vermeltfoort IA1, Raijmakers PG, Riphagen II, Odekerken DA, Kuijper AF, Zwijnenburg A, Teule GJ. Definitions and incidence of cardiac syndrome X: review and analysis of clinical data. Clin Res Cardiol. 2010;99:475–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Beltrame JF, Crea F, Kaski JC, Ogawa H, Ong P, Sechtem U, Shimokawa H, Bairey Merz CN; Coronary Vasomotion Disorders International Study Group (COVADIS). International standardization of diagnostic criteria for vasospastic angina. Eur Heart J. 2015

  11. Members TF, Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A, Bugiardini R, Crea F, Cuisset T, Di Mario C, Ferreira JR, Gersh BJ, Gitt AK, Hulot JS, Marx N, Opie LH, Pfisterer M, Prescott E, Ruschitzka F, Sabaté M, Senior R, Taggart DP, van der Wall EE, Vrints CJ, ESC Committee for Practice Guidelines, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Document Reviewers, Knuuti J, Valgimigli M, Bueno H, Claeys MJ, Donner-Banzhoff N, Erol C, Frank H, Funck-Brentano C, Gaemperli O, Gonzalez-Juanatey JR, Hamilos M, Hasdai D, Husted S, James SK, Kervinen K, Kolh P, Kristensen SD, Lancellotti P, Maggioni AP, Piepoli MF, Pries AR, Romeo F, Rydén L, Simoons ML, Sirnes PA, Steg PG, Timmis A, Wijns W, Windecker S, Yildirir A, Zamorano JL. 2013 ESC guidelines on the management of stable coronary artery disease: the task force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013;34:2949–3003.

    Article  Google Scholar 

  12. Pizzi C, Manfrini O, Fontana F, Bugiardini R. Angiotensin-converting enzyme inhibitors and 3-hydroxy-3-methylglutaryl coenzyme a reductase in cardiac syndrome X: role of superoxide dismutase activity. Circulation. 2004;109:53–8.

    Article  CAS  PubMed  Google Scholar 

  13. Chen JW1, Hsu NW, Wu TC, Lin SJ, Chang MS. Long-term angiotensin-converting enzyme inhibition reduces plasma asymmetric dimethylarginine and improves endothelial nitric oxide bioavailability and coronary microvascular function in patients with syndrome X. Am J Cardiol. 2002;90:974–982.

  14. Pauly DF, Johnson BD, Anderson RD, Handberg EM, Smith KM, Cooper-DeHoff RM, Sopko G, Sharaf BM, Kelsey SF, Merz CN, Pepine CJ. 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). Am Heart J. 2011;162:678–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kayikcioglu M, Payzin S, Yavuzgil O, Kultursay H, Can LH, Soydan I. Benefits of statin treatment in cardiac syndrome-X. Eur Heart J. 2003;24:1999–2005.

    Article  CAS  PubMed  Google Scholar 

  16. Fábián E, Varga A, Picano E, Vajo Z, Rónaszéki A, Csanády M. Effect of simvastatin on endothelial function in cardiac syndrome X patients. Am J Cardiol. 2004;94:652–5.

    Article  PubMed  Google Scholar 

  17. Zhang X1, Li Q, Zhao J, Li X, Sun X, Yang H, Wu Z, Yang J. Effects of combination of statin and calcium channel blocker in patients with cardiac syndrome X. Coron Artery Dis. 2014;25:40–4.

    Article  PubMed  Google Scholar 

  18. Lanza GA, Colonna G, Pasceri V, Maseri A. Atenolol versus amlodipine versus isosorbide-5-mononitrate on anginal symptoms in syndrome X. Am J Cardiol. 1999;84:854–6.

    Article  CAS  PubMed  Google Scholar 

  19. Sen N, Tavil Y, Erdamar H, Yazici HU, Cakir E, Akgül EO, Bilgi C, Erbil MK, Poyraz F, Okyay K, Turfan M, Cemri M. Nebivolol therapy improves endothelial function and increases exercise tolerance in patients with cardiac syndrome X. Anadolu Kardiyol Derg. 2009;9:371–9.

    PubMed  Google Scholar 

  20. Russo G, Di Franco A, Lamendola P, Tarzia P, Nerla R, Stazi A, Villano A, Sestito A, Lanza GA, Crea F. Lack of effect of nitrates on exercise stress test results in patients with microvascular angina. Cardiovasc Drugs Ther. 2013;27:229–34.

    Article  CAS  PubMed  Google Scholar 

  21. Villano A, Di Franco A, Nerla R, Sestito A, Tarzia P, Lamendola P, Di Monaco A, Sarullo FM, Lanza GA, Crea F. Effects of ivabradine and ranolazine in patients with microvascular angina pectoris. Am J Cardiol. 2013;112:8–13.

    Article  CAS  PubMed  Google Scholar 

  22. Mehta PK, Goykhman P, Thomson LE, Shufelt C, Wei J, Yang Y, Gill E, Minissian M, Shaw LJ, Slomka PJ, Slivka M, Berman DS, Bairey Merz CN. Ranolazine improves angina in women with evidence of myocardial ischemia but no obstructive coronary artery disease. JACC Cardiovasc Imaging. 2011;4:514–22.

    Article  PubMed  Google Scholar 

  23. Bairey Merz CN, Handberg EM, Shufelt CL, Mehta PK, Minissian MB, Wei J, Thomson LE, Berman DS, Shaw LJ, Petersen JW, Brown GH, Anderson RD, Shuster JJ, Cook-Wiens G, Rogatko A, Pepine CJ. A randomized, placebo-controlled trial of late Na current inhibition (ranolazine) in coronary microvascular dysfunction (CMD): impact on angina and myocardial perfusion reserve. Eur Heart J. 2016;37:1504–13.

    Article  PubMed  Google Scholar 

  24. Jadhav S, Ferrell W, Greer IA, Petrie JR, Cobbe SM, Sattar N. Effects of metformin on microvascular function and exercise tolerance in women with angina and normal coronary arteries: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol. 2006;48:956–63.

    Article  CAS  PubMed  Google Scholar 

  25. Chen JW, Lee WL, Hsu NW, Lin SJ, Ting CT, Wang SP, Chang MS. Effects of short-term treatment of nicorandil on exercise-induced myocardial ischemia and abnormal cardiac autonomic activity in microvascular angina. Am J Cardiol. 1997;80:32–8.

    Article  CAS  PubMed  Google Scholar 

  26. Kühl JT, George RT, Mehra VC, Linde JJ, Chen M, Arai AE, Di Carli M, Kitagawa K, Dewey M, Lima JA, Kofoed KF. Endocardial-epicardial distribution of myocardial perfusion reserve assessed by multidetector computed tomography in symptomatic patients without significant coronary artery disease: insights from the CORE320 multicentre study. Eur Heart J Cardiovasc Imaging 2015.

  27. Reriani M, Raichlin E, Prasad A, Mathew V, Pumper GM, Nelson RE, Lennon R, Rihal C, Lerman LO, Lerman A. Long-term administration of endothelin receptor antagonist improves coronary endothelial function in patients with early atherosclerosis. Circulation. 2010;122:958–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Fukumoto Y, Mohri M, Inokuchi K, Ito A, Hirakawa Y, Masumoto A, Hirooka Y, Takeshita A, Shimokawa H. Anti-ischemic effects of fasudil, a specific rho-kinase inhibitor, in patients with stable effort angina. J Cardiovasc Pharmacol. 2007;49:117–21.

    Article  CAS  PubMed  Google Scholar 

  29. Shimokawa H, Sunamura S, Satoh K. RhoA/rho-kinase in the cardiovascular system. Circ Res. 2016;118:352–66.

    Article  CAS  PubMed  Google Scholar 

  30. Murthy VL, Naya M, Taqueti VR, Foster CR, Gaber M, Hainer J, Dorbala S, Blankstein R, Rimoldi O, Camici PG, Di Carli MF. Effects of sex on coronary microvascular dysfunction and cardiac outcomes. Circulation. 2014;129:2518–27.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors are grateful to Sabine Nägele for excellent secretarial support.

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Authors and Affiliations

  1. Department of Cardiology, Robert-Bosch-Krankenhaus, 110, 70376, Stuttgart, Germany

    Peter Ong, Anastasios Athanasiadis & Udo Sechtem

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  1. Peter Ong
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  3. Udo Sechtem
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Correspondence to Peter Ong.

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Ong, P., Athanasiadis, A. & Sechtem, U. Treatment of Angina Pectoris Associated with Coronary Microvascular Dysfunction. Cardiovasc Drugs Ther 30, 351–356 (2016). https://doi.org/10.1007/s10557-016-6676-z

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  • DOI: https://doi.org/10.1007/s10557-016-6676-z

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