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Coronary Microembolization—Its Role in acute coronary syndromes and interventions

Koronate Mikroembolisierung — Bedeutung bei akuten koronaren Syndromen und bei interventionellen Eingriffen

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Abstract

The diagnosis coronary artery disease is classically based on patient’s symptoms and morphology, as analyzed by angiography. The importance of risk factors for the development of coronary atherosclerosis and disturbance of coronary vasomotion is clearly established. However, micorembolization of the coronary circulation has also to be taken into account. Microembolization may occur as a single or as multiple, repetitive events, and it may induce inflammatory responses. Spontaneous microembolization may occur, when the fibrous cap of an atheroma or fibroatheroma (Stary IV and Va) ruptures and the lipid pool with or without additional thrombus formation is washed out of the atheroma into the microcirculation. Such events with progressive thrombus formation are known as cyclic flow variations. Plaque rupture occurs more frequenty than previously assumed, i. e. in 9% of patients without known heart disease suffering a traffic accident and in 22% of patients with hypertension and diabetes. Also, in patients dying from sudden death microembolization is frequently found. Patients with stable and unstable angina show not only signs of coronary plaque rupture and thrombus formation, but also microemboli and microinfarcts, the only difference between those with stable and unstable angina being the number of events. Appreciation of microembolization may help to better understand the pathogenesis of ischemic cardiomyopathy, diabetic cardiomyopathy and acute coronary syndromes, in particular in patients with normal coronary angiograms, but plaque rupture detected by intravascular ultrasound. Also, the benefit from glycoprotein IIb/IIIa receptor antagonist is better understood, when not only the prevention of thrombus formation in the epicardial atherosclerotic plaque, but also that of microemboli is taken into account. Microembolization also occurs during PTCA, inducing elevations of troponin T and I and elevations of the ST segment in the EKG. Elevated baseline coronary blood flow velocity, as a potential consequence of reactive hyperemia in myocardium surrounding areas of microembolization, is more frequent in patients with high frequency rotablation than in patients with stenting and in patients with PTCA. The hypothesis of iatrogenic microembolization during coronary interventions is now supported by the use of aspiration and filtration devices, where particles with a size of up to 700μm have been retrieved.

In the experiment, microembolization is characterized by perfusion-contraction mismatch, as the proportionate reduction of flow and function seen with an epicardial stenosis is lost and replaced by contractile dysfunction in the absence of reduced flow.

The analysis of the coronary microcirculation, in addition to that of the morphology and function of epicardial coronary arteries, and in particular appreciation of the concept of microembolization will further improve the understanding of the pathophysiology and clinical symptoms of coronary artery disease.

Zusammenfassung

Die klassische Diagnose der koronaren Herzerkrankung stützt sich auf die Symptome, die Morphologie der Koronargefäße und die Bewertung der koronaren Vasomotion. Sowohl für die Entwicklung der Koronarsklerose als auch für die gestörte Vasomotion ist die Bedeutung der Risikofaktoren analysiert und gewichtet worden. In die Betrachtung der Pathogenese der koronaren Herzerkrankung muß jedoch die Mikroembolisierung des Myokards, die als Einzelereignis oder in multiplen Episoden auftreten kann, neu aufgenommen werden. Die Ereignisse können während des Lebens repetitiv und periodisch entstehen und Entzündungstreaktion auslösen oder verstärken. Spontan sind diese Mikroembolisierungen zu beobachten, wenn die fibröse Kappe im Stadium des Atheroms oder Fibroatheroms (Stary IV und Va) einreißt und der Lipidkern mit oder ohne Thrombusbildung embolisiert. Diese Effekte können bei eine Koronarstenose durch progressive Thrombusbildungen, die sich wieder ablösen und neu aufbauen können, verstärkt werden. Plaquerupturen sind häufiger als vermutet und sind auch bei Gesunden zu beobachten. Sie werden in 9% der Unfallopfer ohne manifeste Herzerkrankungen, aber in 22% bei Patienten mit Hypertonie und Diabetes aufgedeckt. Bei Patienten mit plötzlichem Herztod werden regelmäßig periphere Mikroembolisierungen nachgewiesen. Patienten mit stabiler und unstabiler Angina pectoris unterscheiden sich nur in der Zahl der Mikroinfarkte. Dies bedeutet, daß die koronare Herzerkrankung in ihrer Vielfalt besser verstanden wird, wenn auch die Möglichkeit einer Mikroembolisierung mit berücksichtigt wird, so für die Erklärung einer ischämischen Kardiomyopathie, einer diabetischen Kardiomyopathie, der akuten Koronarsyndrome, zum Beispiel mit normalem Koronarogramm. Das Verständnis der Mikroembolisierungen öffnet auch neue Perspektiven in der Strategie zur Stabilisierung einer vulnerablen Plaque, da bei der Plaqueruptur nicht nur die Möglichkeit der inkompletten oder kompletten Thrombusbildung. sondern auch die Verhinderung einer Mikroembolisierung diskutiert werden muß. Der therapeutische Benefit, insbesondere des Glykoprotein-IIb/IIIa-Rezeptor Antagonisten Abxicimab (Rheo Pro®), beruht auf einer Blockade der Bildung von Thromben, aufgepfropft auf atherosklerotischen Plaques und/oder Mikroembolien. Es wird vermutet, daß auch periinterventionell Mikroembolisierungen auftreten und Mikroinfarkte auslösen können, die zu CK−, Troponin-T-und/oder-I-Erhöhung und EKG-Veränderungen führen könen. Als Hinweis auf eine mögliche Mikroembolisierung ist der Nachweis einer erhöhten basalen Flußgeschwindigkeit nach Intervention gewertet worden, da er experimentell nach Mikroembolisierung beschrieben worden ist. Diese Hypothese ist durch die Verwendung von Aspirations- und Filtersystemen nun bewiesen worden. Überraschend zahlreich waren die aufgefangenen Partikel, die bis zu 700 μm Länge aufwiesen. Die Bedeutung der Mikroembolisierung wird dazu führen, daß bei nachgewiesenen Thromben oder Plaquerupturen neue interventionelle Techniken genutzt werden, um eine Mikroembolisierung zu verhindern. Neben dem Einsatz von Filtersystemen stehen auch Graft-Stents zur Verfügung.

Die Analyse der Morphologie und Funktion epikardialer Gefäße wird durch die Betrachtung der mikrovaskulären Strombahn ergänzt und vervollständigt das Bild der Koronaren Herzerkrankung.

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Authors and Affiliations

  1. Department of Cardiology, Division of Internal Medicine, University, Hufelandstraße 55, D-45122, Essen, Germany

    Raimund Erbel MD, FACC, FESC (Professor of Medicine/Cardiology)

  2. Department of Pathophysiology, Division of Internal Medicine, University Essen, Germany

    Gerd Heusch

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  1. Raimund Erbel MD, FACC, FESC
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  2. Gerd Heusch
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Correspondence to Raimund Erbel MD, FACC, FESC.

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Supported by the German Research Foundation E-155/4-2.

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Erbel, R., Heusch, G. Coronary Microembolization—Its Role in acute coronary syndromes and interventions. Herz 24, 558–575 (1999). https://doi.org/10.1007/BF03044228

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