Skip to main content

Advertisement

SpringerLink
Log in

Koronare mikrovaskuläre Dysfunktion

Klinik, Diagnose, Therapie

Coronary microvascular dysfunction

Clinical aspects, diagnosis and therapy

  • CME Zertifizierte Fortbildung
  • Published:
Der Kardiologe Aims and scope

Zusammenfassung

Wie durch epikardiale Stenosen entsteht auch durch eine koronare mikrovaskuläre Dysfunktion (KMD) ein Missverhältnis zwischen myokardialem Sauerstoffbedarf und -angebot. Die Fehlfunktion liegt auf Ebene der Gefäße mit einem Durchmesser von < 500 μm, und sowohl strukturelle als auch funktionelle Veränderungen der Gefäße sind beschrieben worden. Die zugrunde liegenden Mechanismen sind vielfältig und zum Teil zusammen auftretend, aber noch nicht komplett verstanden und umfassen unter anderem eine chronische Inflammation, Östrogenmangel oder eine genetische/familiäre Prädisposition. Klinisch ist eine KMD häufig bei Patienten mit Angina pectoris und/oder Dyspnoe anzutreffen, die keine relevanten Koronarstenosen oder Myokarderkrankungen aufweisen. Dieses Krankheitsbild wird zurzeit noch zu wenig berücksichtigt. Studien haben nämlich gezeigt, dass eine solche KMD bei ca. 50 % aller Patienten mit Angina pectoris und nicht stenosierten Koronararterien vorliegen kann. Für die Diagnosestellung kommen nichtinvasive Verfahren wie die Kombination aus Koronar-CT und Stress-MRT oder Koronar-CT und PET, aber auch invasive Vasomotionstestungen (koronare Flussreserve mit Adenosin, Acetylcholin-Test) infrage. Bezüglich der Effektivität einer medikamentösen Therapie gibt es bislang nur sehr wenig Evidenz. Die Leitlinie der Europäischen Gesellschaft für Kardiologie (ESC) zum Management der stabilen koronaren Herzkrankheit von 2013 empfiehlt eine Sekundärprophylaxe mit ASS und einem Statin sowie eine β-Blocker- und/oder Kalziumantagonistentherapie. Patienten mit KMD haben ein erhöhtes Risiko für Koronarereignisse und Tod von ca. 1,7 % pro Jahr. Außerdem besteht eine erhöhte Morbidität mit häufigen Vorstellungen in Praxis und Notaufnahme. Die klinische Forschung in diesem Bereich hat eine genauere Charakterisierung der zugrunde liegenden Mechanismen der mikrovaskulären Dysfunktion zum Ziel, um hieraus gezieltere Therapiekonzepte ableiten zu können.

Abstract

Just like epicardial coronary stenosis, coronary microvascular dysfunction (CMD) leads to an imbalance of myocardial oxygen demand and supply. The dysfunction is located at the level of the coronary microcirculation with a vessel diameter of < 500 µm and structural as well as functional alterations have been described. The underlying mechanisms are diverse, frequently overlapping and still incompletely understood. Among others, conditions such as chronic inflammation, estrogen deficiency and genetic predisposition have been reported. A common and often underdiagnosed clinical manifestation of CMD is in patients who have symptoms of angina but no obstructive epicardial coronary artery disease or myocardial disease. The CMD can be diagnosed using non-invasive tools such as the combination of coronary computed tomography (CT) and cardiac imaging stress test or coronary CT and positron emission tomography (PET). In addition, invasive coronary vasomotor assessment (e.g. coronary flow reserve measurements in response to adenosine or acetylcholine provocation testing) are also suitable. There are still very few data regarding the effectiveness of pharmacological treatments for CMD. The current European Society of Cardiology (ESC) guidelines on the management of stable coronary artery disease suggest using aspirin and statins as well as beta blockers and/or calcium channel blockers. Patients with CMD have an elevated risk for coronary events and death of approximately 1.7 % per year. Moreover, there is an increased morbidity with frequent presentations in practice and emergency admissions. Clinical research efforts should aim at a better characterization of the underlying mechanisms in patients with CMD in order to develop tailored treatment approaches.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3

Literatur

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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Rosano GM, Collins P, Kaski JC et al (1995) Syndrome X in women is associated with oestrogen deficiency. Eur Heart J 16:610–614

    CAS  PubMed  Google Scholar 

  3. Fedele F, Mancone M, Chilian WM et al (2013) Role of genetic polymorphisms of ion channels in the pathophysiology of coronary microvascular dysfunction and ischemic heart disease. Basic Res Cardiol 108:387

    Article  PubMed Central  PubMed  Google Scholar 

  4. Schannwell CM, Steiner S, Strauer BE (2005) Hypertensive mikrovaskuläre Erkrankung. Herz 30:26–36

    Article  PubMed  Google Scholar 

  5. Camici PG, Crea F (2007) Coronary microvascular dysfunction. N Engl J Med 356:830–840

    Article  CAS  PubMed  Google Scholar 

  6. Crea F, Camici PG, Bairey Merz CN (2014) Coronary microvascular dysfunction: an update. Eur Heart J 35:1101–1111

    Article  PubMed  Google Scholar 

  7. Patel MR, Peterson ED, Dai D et al (2010) Low diagnostic yield of elective coronary angiography. N Engl J Med 362:886–895

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Jespersen L, Hvelplund A, Abildstrøm SZ et al (2012) Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J 33:734–744

    Article  PubMed  Google Scholar 

  9. Reis SE, Holubkov R, Conrad Smith AJ et al (2001) 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 141:735–741

    Article  CAS  PubMed  Google Scholar 

  10. Ong P, Athanasiadis A, Borgulya G et al (2012) 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 59:655–662

    Article  CAS  PubMed  Google Scholar 

  11. Sambuceti G, Parodi O, Marcassa C et al (1993) Alteration in regulation of myocardial blood flow in one-vessel coronary artery disease determined by positron emission tomography. Am J Cardiol 72:538–543

    Article  CAS  PubMed  Google Scholar 

  12. Pupita G, Maseri A, Kaski JC et al (1990) Myocardial ischemia caused by distal coronary-artery constriction in stable angina pectoris. N Engl J Med 323:514–520

    Article  CAS  PubMed  Google Scholar 

  13. Ong P, Athanasiadis A, Perne A et al (2014) Coronary vasomotor abnormalities in patients with stable angina after successful stent implantation but without in-stent restenosis. Clin Res Cardiol 103:11–19

    Article  PubMed  Google Scholar 

  14. Ong P, Athanasiadis A, Mahrholdt H et al (2012) Increased coronary vasoconstrictor response to acetylcholine in women with chest pain and normal coronary arteriograms (cardiac syndrome X). Clin Res Cardiol 101:673–681

    Article  CAS  PubMed  Google Scholar 

  15. Kajander S, Joutsiniemi E, Saraste M et al (2010) Cardiac positron emission tomography/computed tomography imaging accurately detects anatomically and functionally significant coronary artery disease. Circulation 122:603–613

    Article  CAS  PubMed  Google Scholar 

  16. Achenbach S, Marwan M, Ropers D et al (2010) Coronary computed tomography angiography with a consistent dose below 1 mSv using prospectively electrocardiogram-triggered high-pitch spiral acquisition. Eur Heart J 31:340–346

    Article  PubMed  Google Scholar 

  17. Task Force Members, Montalescot G, Sechtem U et al (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 34:2949–3003

    Article  Google Scholar 

  18. Galiuto L, Sestito A, Barchetta S et al (2007) Noninvasive evaluation of flow reserve in the left anterior descending coronary artery in patients with cardiac syndrome X. Am J Cardiol 99:1378–1383

    Article  PubMed  Google Scholar 

  19. Ong P, Athanasiadis A, Borgulya G et al (2014) Clinical usefulness, angiographic characteristics and safety evaluation of intracoronary acetylcholine provocation testing among 921 consecutive caucasian patients with unobstructed coronary arteries. Circulation 129:1723–1730

    Article  CAS  PubMed  Google Scholar 

  20. Noto TJ Jr, Johnson LW, Krone R et al (1991) Cardiac catheterization 1990: a report of the Registry of the Society for Cardiac Angiography and Interventions (SCA&I). Cathet Cardiovasc Diagn 24:75–83

    Article  PubMed  Google Scholar 

  21. Vermeltfoort IA, Raijmakers PG, Riphagen II et al (2010) Definitions and incidence of cardiac syndrome X: review and analysis of clinical data. Clin Res Cardiol 99:475–481

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Pauly DF, Johnson BD, Anderson RD et al (2011) 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 162:678–684

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Kayikcioglu M, Payzin S, Yavuzgil O et al (2003) Benefits of statin treatment in cardiac syndrome-X1. Eur Heart J 24:1999–2005

    Article  CAS  PubMed  Google Scholar 

  24. Lanza GA, Colonna G, Pasceri V, Maseri A (1999) Atenolol versus amlodipine versus isosorbide-5-mononitrate on anginal symptoms in syndrome X. Am J Cardiol 84:854–856

    Article  CAS  PubMed  Google Scholar 

  25. Ozçelik F, Altun A, Ozbay G (1999) Antianginal and anti-ischemic effects of nisoldipine and ramipril in patients with syndrome X. Clin Cardiol 22:361–365

    Article  PubMed  Google Scholar 

  26. Russo G, Di Franco A, Lamendola P et al (2013) Lack of effect of nitrates on exercise stress test results in patients with microvascular angina. Cardiovasc Drugs Ther 27:229–234

    Article  CAS  PubMed  Google Scholar 

  27. Albertsson PA, Emanuelsson H, Milsom I (1996) Beneficial effect of treatment with transdermal estradiol-17-beta on exercise-induced angina and ST segment depression in syndrome X. Int J Cardiol 54:13–20

    Article  CAS  PubMed  Google Scholar 

  28. Chen JW, Lee WL, Hsu NW et al (1997) Effects of short-term treatment of nicorandil on exercise-induced myocardial ischemia and abnormal cardiac autonomic activity in microvascular angina. Am J Cardiol 80:32–38

    Article  CAS  PubMed  Google Scholar 

  29. Rogacka D, Guzik P, Wykretowicz A et al (2000) Effects of trimetazidine on clinical symptoms and tolerance of exercise of patients with syndrome X: a preliminary study. Coron Artery Dis 11:171–177

    Article  CAS  PubMed  Google Scholar 

  30. Jadhav S, Ferrell W, Greer IA et al (2006) 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 48:956–963

    Article  CAS  PubMed  Google Scholar 

  31. Mehta PK, Goykhman P, Thomson LE et al (2011) Ranolazine improves angina in women with evidence of myocardial ischemia but no obstructive coronary artery disease. JACC Cardiovasc Imaging 4:514–522

    Article  PubMed  Google Scholar 

  32. Ong P, Konopka N, Mahrholdt H et al (2013) ABSTRACT: P478 – 4-year follow-up of patients with stable angina, unobstructed coronary arteries and proof of coronary artery spasm: the ACOVA study follow-up. Clin Res Cardiol 102(Suppl 1). doi:10.1007/s00392-013-1100-1

  33. Shaw LJ, Merz CN, Pepine CJ et al (2006) 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 114:894–904

    Article  PubMed  Google Scholar 

  34. Jespersen L, Abildstrøm SZ, Hvelplund A, Prescott E (2013) 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 102:571–581

    Article  PubMed  Google Scholar 

  35. Jespersen L, Abildstrøm SZ, Hvelplund A et al (2013) Symptoms of angina pectoris increase the probability of disability pension and premature exit from the workforce even in the absence of obstructive coronary artery disease. Eur Heart J 34:3294–3303

    Article  PubMed  Google Scholar 

  36. Lamendola P, Lanza GA, Spinelli A et al (2010) Long-term prognosis of patients with cardiac syndrome X. Int J Cardiol 140:197–199

    Article  PubMed  Google Scholar 

  37. Halcox JP, Schenke WH, Zalos G et al (2002) Prognostic value of coronary vascular endothelial dysfunction. Circulation 106:653–658

    Article  PubMed  Google Scholar 

  38. Pepine CJ, Anderson RD, Sharaf BL et al (2010) 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 55:2825–2832

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Jespersen L, Hvelplund A, Abildstrøm SZ et al (2012) Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J 33:734–744

    Article  PubMed  Google Scholar 

  40. Johnson BD, Shaw LJ, Pepine CJ et al (2006) Persistent chest pain predicts cardiovascular events in women without obstructive coronary artery disease: results from the NIH-NHLBI-sponsored Women’s Ischaemia Syndrome Evaluation (WISE) study. Eur Heart J 27:1408–1415

    Article  PubMed  Google Scholar 

Download references

Danksagung

Die Autoren danken Frau S. Nägele für organisatorische Unterstützung beim Erstellen des Manuskriptes.

Einhaltung ethischer Richtlinien

Interessenkonflikt. P. Ong und U. Sechtem geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

Author information

Authors and Affiliations

  1. Abteilung für Kardiologie, Zentrum für Innere Medizin III, Robert-Bosch-Krankenhaus, Auerbachstr. 110, 70376, Stuttgart, Deutschland

    P. Ong & U. Sechtem

Authors
  1. P. Ong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. U. Sechtem
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. Ong.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ong, P., Sechtem, U. Koronare mikrovaskuläre Dysfunktion. Kardiologe 9, 187–196 (2015). https://doi.org/10.1007/s12181-014-0616-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12181-014-0616-6

Schlüsselwörter

Keywords

Search

Navigation