A review of evidence against a single mechanism to explain reduced coronary flow as reflected by the presence of ST segment depression and elevation   

J. B. Nasmith¹, J. G. Diodati², C. Pharand^2
1Toronto Western Hospital, University of Toronto, 399 Bathurst Street, Toronto, Ontario, CANADA M5T 2S8
²Hopital du Sacré-Coeur, Université de Montréal,
5400 boul. Gouin ouest, Montréal, Québec, CANADA H4J 1C5.

INTRODUCTION

The presence of ST segment elevation is crucial to the urgent pursuit of arterial reperfusion in acute coronary syndromes. Clinically validated, this modern imperative rests soundly on the classic association between ST elevation and critical transmural ischemia due to proximal coronary occlusion. By contrast, treatment and rational are controversial in acute ischemic events that lack ST elevation.

Popular wisdom attributes absent or depressed ST shifts (non-ST-elevation ischemia) to reductions in coronary flow that are moderate resulting from non critical epicardial stenosis, which cause only modest falls in perfusion pressure.  Subsequent clinical events are believed to result from thrombotic progression to transient total occlusion as in ST elevation events. This paper seeks to   show how evidence contradicts this view and why the mechanisms of coronary resistance during ST depression need reconsideration.

LABORATORY MODELS

Animal models employing moderate coronary stenosis fail to induce ST depression unless tachycardia is employed. While these conditions may correspond to exercise ischemia (and high heart rates during ambulatory monitoring) they bear little resemblance to patients presenting with unstable angina or non-Q-wave MI where ST depression appears at normal or low heart rates.

CLINICAL CONTRADICTIONS

Clinical observations often fail to support the theory that non-ST-elevation ischemic events are just lesser versions of ST elevation pathology. Patients without rather than with ST elevation are older, more often diabetic and have more chronic and diffuse disease. The ST subtypes have entirely different responses to thrombolytic therapy. Finally, the incidence of short- and immediate-term recurrent clinical events differs markedly following the two ECG presentations. Together, these observations have raised the possibility of uniqueness in the histological character of the lesions involved.

Opponents against 2 distinct pathologies argue that collateral vessels promoted by diffuse disease account for subendocardial ischemia and ST depression. They propose that platelet re-activation and cerebral haemorrhage outweigh modest gains by thrombolysis in vessels that were never fully occluded.  And they dismiss early prognostic differences on greater myocardial vulnerability in incomplete infarction rather than distinct  recidivism dwelling within the plaque.

ECG EVIDENCE

Of further note, it is rare for one ST type to convert to the other during the same coronary syndrome. That is, as thrombolysis progressively restores proximal coronary flow, it would seem reasonable by conventional thinking that ST elevation would progress to ST depression as ischemia decreased from transmural to subendocardial before perfusion and repolarization become normal. This is seen in only the most exceptional instances.

Furthermore, in unstable angina patients, recurrent ischemic episodes usually occur with the same ST shift direction as in previous episodes. This contradicts conventional wisdom which presumes that as lesion severity waxes and wanes (the accepted basis of unstable syndromes), ST deflections should reflect critical and then less severe obstructions by switching from positive to negative ST shifts.  The remarkable fidelity to one or to the other ST polarity seems to denote some innate and consistent pathophysiology the culprit lesion rather than just the severity of the stenosis.

RECENT ANGIOGRAPHIC FINDINGS

In recent decades the non-ST-elevation ischemic presentation has become the predominant acute coronary syndrome. Although recurrent chest pain and ST depression and myocardial enzyme release are frequent findings in these patients, acute angiography uncovers culprit vessel stenosis to be surprising modest (70%) and arterial flow to be remarkably robust (TIMI Grade III). 

Despite this, popular management has targeted the anatomy of the proximal stenosis with mechanical strategies.  Without doubt, angiographic images of epicardial defects are visually compelling so that thinking has been steered away from concepts of physiology such as vasomotion in resistance vessels.  Recently, invasive techniques that measure downstream resistance have re-kindled interest in myocardial ischemia due to small vessel pathology.  For example, a recent angiographic study in the acute phase of unstable angina has demonstrated increased small vessel resistance during attacks of chest pain.

In another report, stable angina patients with significant coronary stenosis undergoing atrial pacing demonstrated increased microvascular resistance and ST depression that was decreased by intra coronary adenosine. Lastly, detailed angiographic analysis of coronary artery spasm confirmed that ST elevation corresponded to proximal coronary spasm but that ST depression was seen during small vessel vasoconstriction.

CONCLUSION

The evidence better supports that there may be two perfusion mechanisms at play in the generation of the two ischemic ST phenomena. One entails the classic notion of critical resistance resulting from total or near complete epicardial occlusion, which inflicts critical flow reduction in a transmyocardial distribution with it ST elevation signature.

The second mechanism might result from small vessel vasoconstriction.  If the effect across the ventricular wall were non-uniform, the stage would be set for selective subendocardial hypoperfusion and telltale ST depression. 

The question therefore, arises as to whether an unstable coronary lesion has innate characteristics that dictate either the role of occluder in proximal segments or the role of vasoconstrictor in downstream beds. The latter would rarely plug proximal segments…the stated but rarely substantiated menace that drives the invasive assault on unstable angina in modern practice. If confirmed, newly developed antagonists to the vasomotion component of unstable coronary disease might diminish the need for invasive treatments.  And the ST segment might lead the way.

REFERENCES

[1]  P. Theroux, V. Fuster. “Acute Coronary Syndromes, Unstable Angina and Non-Q-Waves Myocardial Infarction,” Circulation 97, pp. 1195-205, 1998.

[2]  P.W. Armstrong, F. Yuling, W.C. Chang. “Acute Coronary Syndomes in the GUSTO-IIb Trial,” Circulation 98, pp. 1860-68, 1998.

[3] M. Marzilli, G. Sambuceti, S. Fedele, “Coronary Microcirculatory Vasoconstriction During Ischemia in Patients With Unstable Angina,” J Am Coll Cardiol 35, pp. 327-34, 2000.

[4] G. Sambuceti, M. Marzelli, S. Fedele, Paradoxical Increase in Microvascular resistance During Tachycardia Downstream From a Severe Stenosis in Patients With Coronary Artery Disease,” Circulation 103, pp. 2352-60, 2001.

[5] H. Sun, M. Mohri, H. Shimokawa, “Coronary Microvascular Spasm Causes Myocardial Ischemia in Patients With Vasospastic Angina,” J Am Coll Cardiol 39, pp. 847-51, 2002.