It Takes Time to Heal a Broken Heart
To the Editor:
The excellent article “Coronary Angioscopic Findings in the Infarct-Related Vessel Within 1 Month of Acute Myocardial Infarction: Natural History and the Effect of Thrombolysis” by Eric Van Belle and coworkers1 in the January 6/13, 1998, issue of Circulation takes on special significance today. Although managed care (MC) stands at the forefront of decision making, MC must not be allowed to cancel the significance of the biology of healing. Their article demonstrates that the vascular lesion responsible for myocardial infarction requires a longer time for healing than has been appreciated by most modern cardiologists.
Although previous studies had already demonstrated that acute infarction of the cardiac muscle requires weeks, not days, to heal,2 modern textbooks of clinical cardiology provide little emphasis for that essential process. Nuclear changes begin in infarcting muscle within hours and continue for at least 10 days. Necrosis and phagocytosis of muscle fibers persist for ≥3 weeks. Neutrophiles and basophiles continue to proliferate for 2 to 3 weeks, at which time macrophages come in and proliferate for >6 weeks.
Now Van Belle and colleagues have demonstrated angioscopically that “healing of the infarct-related [arterial] lesion requires more than 1 month and that an ‘unstable’ yellow plaque with adherent thrombus is common during that period … [and] may partly explain the unique behavior of recent infarct-related lesions, which are more prone to occlude than other lesions.”
These new angioscopic findings reinforce the need for essential attention to the time required for healing and provide explanation for the substantial number of deaths that occur after the first 2 days after coronary occlusion.3 4 Early discharge conceals a substantial number of patients with infarct who are destined to die after intrahospital study (41% to 60%). Early discharge deprives them of the potential life-saving benefits of early detection of dysrhythmia and timely treatment by control of pump failure (including intra-aortic balloon pumping, management of recurrent infarction, and cardioversion with cardiopulmonary resuscitation); such lives could have been salvaged if the patient had been under adequate surveillance with life-saving equipment, whether in hospital or otherwise. Family survivors are often hard pressed to accept these later deaths, and managing physicians may be at a loss to explain their occurrence after the elaborate treatments provided in the hospital period. This important angioscopic study can help!
- Copyright © 1999 by American Heart Association
Van Belle E, Lablanche J-M, Bauters C, Renaud N, McFadden EP, Bertrand ME. Coronary angioscopic findings in the infarct-related vessel within 1 month of acute myocardial infarction: natural history and the effect of thrombolysis. Circulation. 1998;97:26–33.
Wehrmacher WH. Pain in the Chest. Springfield, Ill: Charles C Thomas, Publisher; 1964:152.
Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2: Second International Study of Infarct Survival. Lancet. 1988;2:349–360.
Brodie BR, Stuckey T, Hansen CJ, Muncy DB, Weintraub RA, Kelly TA, Berry JJ. Timing and mechanism of death determined clinically after primary angioplasty for acute myocardial infarction. Am J Cardiol. 1997;79:1586–1591.
We welcome the opportunity to respond to the letter from Drs Wehrmacher and Lewis regarding our article in which we showed that the majority of infarct-related lesions had angioscopic evidence of instability, a complex surface with thrombus, when studied during the first month after myocardial infarction.R1
We agree with them that “the vascular lesion responsible for myocardial infarction requires a longer time for healing that has been appreciated by most modern cardiologists.” This may explain the tendency of infarct-related arteries to reocclude and the high frequency of adverse thrombotic events observed late (>10 days) after acute myocardial infarction (MI). As they suggest, part of the solution may be to monitor patients for a longer period of time in order to treat them appropriately when such an adverse event occurs. However, from a practical standpoint, it is not possible to keep these patients in the hospital for the time required for the culprit lesion to heal (>1 month).
Ultimately, the ideal solution would be to prevent the occurrence of thrombotic events. Our observation of persistent “plaque instability” for weeks after acute MI provides a new potential target to achieve this goal. This could be accomplished either by (1) passivation of the plaque during the time period required for healing or (2) acceleration of the healing process itself. Plaque passivation could be achieved by drugs designed to eliminate thrombus from the unstable plaque. Although the results of the EPIC trialR2 demonstrated proof of the concept of plaque passivation using glycoprotein IIb/IIIa antagonists, it is likely that such a short duration of intravenous treatment will be insufficient to prevent late thrombus formation and related events after MI. The development of oral forms of glycoprotein IIb/IIIa antagonists will open new perspectives, and it will be important to test these drugs in this setting. Acceleration of the healing process could be achieved by mechanical means. Indeed, implantation of a stent, by virtue of its scaffolding properties, may mechanically seal the ulcerated segment and exclude the thrombus from the lumen, leading to “mechanical healing.” The recent demonstration of a reduction in late vessel occlusion of the infarct-related lesion by stent implantationR3 tends to validate this theory and supports the use of stents in this situation. Importantly, the results of the EPISTENT trial,R4 by showing a benefit of abciximab used in conjunction with stent implantation, lead us to expect that the combination of the pharmacological and mechanical approaches will provide additive effects.
Overall, our observation of persistent plaque instability for weeks after the occurrence of MI should encourage prospective studies to evaluate strategies designed to target the “unstable plaque” to prevent late thrombotic events. Whether a therapeutic strategy leading to a decrease of late vessel occlusion after MI improves late cardiac survival will also require investigation.
Van Belle E, Lablanche JM, Bauters C, Renaud N, McFadden EP, Bertrand ME. Coronary angioscopic findings in the infarct related vessel within 1 month of acute myocardial infarction: natural history and effect of thrombolysis. Circulation. 1998;97:26–33.
The EPIC Investigators. Prevention of ischemic complications in high-risk angioplasty by a chimeric monoclonal antibody c7E3 Fab fragment directed against the platelet glycoprotein IIb/IIIa receptor. N Engl J Med. 1994;330:956–961.
Bauters C, Lablanche JM, Van Belle E, Niculescu R, Meurice T,Mc Fadden EP, Bertrand ME. Effects of coronary stenting on restenosis and occlusion after angioplasty of the culprit vessel in patients with recent myocardial infarction. Circulation. 1997;96:2854–2858.
The EPISTENT Investigators. Randomised placebo-controlled and balloon-angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein IIb/IIIa blockade. Lancet. 1998;352:87–92.