Download Coronary microembolization

Journal of the American College of Cardiology
© 2000 by the American College of Cardiology
Published by Elsevier Science Inc.
Vol. 36, No. 1, 2000
ISSN 0735-1097/00/$20.00
PII S0735-1097(00)00708-7
BRIEF REVIEW
Coronary Microembolization
Raimund Erbel, MD, FESC, FACC,* Gerd Heusch, MD, FESC, FACC†
Essen, Germany
A series of recent studies identified coronary microembolization as a potential cause of regional myocardial contractile
dysfunction in the absence of an atherosclerotic obstruction
of an epicardial coronary artery that could account for such
dysfunction. This review attempts to provide evidence for
coronary microembolization and analyzes its sources and
consequences.
EVIDENCE FROM POSTMORTEM HISTOLOGY
Experimental platelet and coagulation thrombi with embolization into the coronary microcirculation and subsequent
microinfarction and lethal arrhythmias in the laboratory
animal were described more than three decades ago (1).
Subsequently, microembolization and microinfarcts were
also identified at autopsy of patients with acute coronary
syndromes who had died of sudden cardiac death (2,3).
Atherosclerotic material, including cholesterol crystals,
formed the core and source of thrombi in the microcirculation. Often there was evidence for multiple, recurrent
microinfarcts secondary to atherosclerotic thrombemboli,
particularly in patients with prodromal unstable angina
(2,4,5). Intramyocardial thrombemboli were identified at
autopsy in 15% of patients with ischemic heart disease who
died out of the hospital (3).
EXPERIMENTAL
PATHOPHYSIOLOGY
OF MICROEMBOLIZATION
microembolized area is not reduced, but may actually be
enhanced, secondary to an adenosine-related hyperemia of
the myocardium surrounding the embolized microregions
(11,12). Comparing an epicardial stenosis to microembolization with microspheres of 42 ␮m diameter at identical
degrees of contractile dysfunction, we have recently demonstrated perfusion-contraction mismatch secondary to microvascular obstruction, with severe contractile dysfunction
and no detectable decrease in regional blood flow (13,14).
The profound contractile dysfunction could not be related
to the amount of infarcted myocardium. Therefore, the
mechanical disadvantage from multiple microinfarcts (Fig.
1) with multiple border zones to nonischemic myocardium
appears to be greater than that of a single infarct of the same
volume. Importantly, the inflammatory response to microembolization is also greater than that to inflow reduction,
and inflammatory mediators may contribute to the observed
contractile dysfunction.
Cyclic flow variations are a typical phenomenon in
severely stenotic coronary arteries, with the progressive flow
reduction reflecting the formation of platelet aggregates and
its rapid restoration, reflecting dislodgement of platelet
emboli into the microcirculation (15,16).
CLINICAL EVIDENCE
New imaging techniques, in particular coronary angioscopy
and intravascular ultrasound, have facilitated the detection
of epicardial coronary plaque rupture and ulceration (17–
21). Plaque ulceration, previously often misinterpreted as
With acute coronary arterial inflow reduction by an epicardial coronary artery stenosis, contractile function in the
dependent myocardium is rapidly reduced (6). Within a few
minutes, a new steady state of perfusion-contraction matching (7,8) develops in which regional myocardial function is
reduced in proportion to regional myocardial blood flow,
and such perfusion-contraction matching can be maintained
over several hours (9) and may be the pathophysiological
substrate of hibernating myocardium (10). Experimental
microvascular obstruction by intracoronary injection of inert
particles also induces regional contractile dysfunction, and
the amount of dysfunction is proportionate to the number of
injected particles (11,12). In contrast to an epicardial coronary arterial inflow reduction, baseline blood flow into the
From the *Departments of Cardiology and †Pathophysiology, University of Essen
Medical School, Essen, Germany. The author’s studies were supported by the
German Research Foundation (E 155/4-2) and the IFORES grant 107509-0 of the
University of Essen Medical School, Essen, Germany.
Figure 1. Experimental microinfarct with inflammatory response in a
myocardial area perfused by a small artery that has been embolized with
microspheres of 42 ␮m in diameter. Calibration 50 ␮m.
Erbel et al.
Coronary Microembolization
JACC Vol. 36, No. 1, 2000
July 2000:22–24
23
velocity (33,37,38), reminiscent of the reactive hyperemia
seen with experimental microembolization (11,12).
The best available clinical evidence for microembolization
is probably from use of aspiration and filtration devices, that
is, “ex iuvantibus,” which can retrieve surprisingly large
pieces of plaque debris and thrombotic material and prevent
it from being embolized into the microcirculation (39,40).
In conclusion, putting the available pathologic “anatomic,
experimental” pathophysiologic and clinical evidence together, we propose the following scheme (Fig. 2) of plaque
rupture/thrombosis/microembolization, that ultimately induces the clinical consequences of arrhythmias “up to
sudden death” and, most notably, contractile dysfunction.
Figure 2. Schematic presentation of epicardial plaque fissuring/plaque
rupture/thrombosis inducing embolization of atherosclerotic and thrombotic material into the microcirculation, resulting in arrhythmias, micronecrosis, contractile dysfunction and reduced coronary reserve (modified
from reference 41).
coronary aneurysm (17), is frequently found in patients with
unstable and stable angina (22,23) but also occasionally in
patients with a normal coronary angiogram (24). Apparently, plaque rupture and ulceration are frequent events and
part of the general atherosclerotic process, as confirmed at
autopsy (22,23). The material that is washed out of the
plaque cannot only induce local thrombus formation in the
immediate coronary arterial segment but is also dislodged
into the microcirculation and can cause thrombemboli there
(2). The elevations in creatine kinase (CK), troponin T and
I, which are regarded as signs of micronecrosis in patients
with unstable angina, may just be the consequences of such
microembolization (25,26). Conversely, the efficacy of glycoprotein IIb/IIIa receptor antagonists in this scenario and
in acute myocardial infarction (26) may not only reflect
resolution of the thrombus overlying the ruptured epicardial
plaque but also that of the thrombemboli in the microcirculation (27). Interestingly, as in the above experimental
studies, inflammatory responses are also found in patients
with unstable angina (28), in patients with successful percutaneous transluminal coronary angioplasty (29) and in
documented cases of microembolization (30).
Not only in spontaneous plaque rupture and ulceration,
but also during coronary interventions, microembolization
is, in fact, induced, again leading to myocardial micronecrosis, as reflected by elevated CK and troponin (31,32) as
well as by electrocardiogram changes (32) and to reduced
coronary reserve, as documented with myocardial perfusion
measurements (33). The incidence of such “infarctlets” is
higher in those undergoing rotational atherectomy/
revascularization than it is in those undergoing balloon
angioplasty (34,35). Cyclic flow variations, as seen in animal
experiments (15,16), are a sign predicting immediate complications after angioplasty (36). Interestingly, patients
without normalization of coronary reserve after balloon
angioplasty often have elevated baseline coronary flow
Reprint requests and correspondence: Prof. Dr. Gerd Heusch,
Abteilung fuer Pathophysiologie, Zentrum fuer Innere Medizin,
Universitaetsklinikum Essen, Hufelandstr. 55, 45122 Essen, Germany. E-mail: [email protected].
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