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Clin. Cardiol. 24, 353–354 (2001)
Key words: response variability, thrombolytic therapy, ST-segment-elevation, myocardial infarction, multivessel coronary thrombosis
Anyone who has taken care of a patient with an ST-segment-elevation myocardial infarction and treated the patient with thrombolytic therapy will remember that not all patients respond the way we would like them to respond. Ideally, the ST segment should return to baseline, and the patient should become pain free. When this happens, we congratulate ourselves for limiting the infarction size and preserving myocardium. Unfortunately, this does not happen in every case--the question is why not? I am certain there are multiple explanations. One might be that the drug did not reach the clot that occluded the artery, or that the clot burden was so great that the dose of the drug was not enough to penetrate the entire clot. Another possibility relates to pharmacogenetics, since every patient will not respond the same way to every drug given. This is quite clear when results of large clinical trials--which are generally average results--are analyzed. In every clinical trial there are hyperresponders and nonresponders to any given drug, including thrombolytic therapy. Thus, if the patient fails to respond (improve) to a thrombolytic drug within 30 or 40 minutes, one might consider adding another dose, recognizing that the risk of bleeding may increase. However, since the goal is to get the artery open as soon as possible and reperfuse ischemic myocardium, that judgement must be based on the overall condition of the patient--for example, consider a patient in cardiogenic shock due to an anterior myocardial infarction versus a patient with a stable inferior infarction.
What prompted me to write this editorial was an article in the Italian Heart Journal by Garbo and colleagues on thrombosis of multiple coronary arteries in patients with acute myocardial infarction.1
Admittedly, I had not given much thought to multivessel coronary artery thrombosis until I read this article. The authors present four cases of multivessel thrombotic obstruction of the coronary arteries documented at coronary angiography and subsequently treated with coronary angioplasty. They speculate on the mechanism of multiple-vessel coronary thrombosis and hypothesize that in some patients with evolving "large myocardial infarctions" the size of the infarction may be related to multivessel thrombotic obstruction, possibly due to decreased cardiac output and poor perfusion of other vessels at risk. Another hypothesis is that the inflammatory process associated with acute coronary syndromes and coronary artery thrombus may not be limited to one blood vessel, thus setting up some sort of systemic prothrombotic condition with resultant multiple thromboses. However, the authors freely admit that the cause of acute coronary occlusion of multiple coronary vessels remains elusive and speculative. They also admit that the number of patients who have this problem is unknown and that occurrence is perhaps infrequent.
At any rate, these four cases and the subsequent discussion made me think a bit about our current obsession of focusing on the culprit vessel that may be producing symptoms and causing electrocardiographic changes that one can attack with both thrombolytic therapy and angioplasty.
In an accompanying editorial, Burke and Virmani indicate that multiple acute thrombosis at autopsy varies from 25–50% of lethal acute thrombi.2 However, others have reported considerably fewer multiple coronary thrombi (i.e., less than 10%) in sudden cardiac death patients. Falk, in another accompanying editorial commenting on the reason for multiple-site thrombosis, speculates that several possibilities exist: "(1) activation of smoldering inflammation and plaques with synchronized increase in thrombogenicity; (2) simultaneous triggering of rupture-prone plaques; and (3) simultaneous thrombosis on thrombosis-prone plaques, precipitated by a systemic thrombophilic state." He further suggests that since "atherosclerosis is a systemic disease it needs systemic treatment" and concludes that "a target lesion based approach alone will not eliminate the threat posed by all other existing coronary plaques and their overall risk determines prognosis in the long term."3
What does all of this mean for those of us who see patients with acute myocardial infarction? First, the information made me think about how important it is to use thrombolytic therapy in these patients even though one might opt for acute emergent angioplasty. It has always been my bias that the patient should receive thrombolytic therapy prior to angioplasty if the catheterization laboratory is not immediately available. If the ST segments return to baseline and the patient becomes pain free and the vessels demonstrate TIMI-3 flow, perhaps one can relax (although some believe that angioplasty/stent is good therapy even in this circumstance). If these conditions do not occur, angioplasty of the culprit lesion is certainly warranted. However, we need to begin thinking about the possibility of multiple-site coronary thromboses in patients who are slow responders to thrombolytic therapy. Although it may be a rare clinical finding, we should challenge the single-culprit-vessel concept in patients with unstable coronary artery disease, since, as many have pointed out, this is a systemic disease that needs systemic treatment and a target-lesion-based approach will not limit the threat posed by all other existing coronary plaques.
C. Richard Conti, M.D., M.A.C.C.
Editor-in-Chief
References