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EXPEDITED PUBLICATION

Relationship of Thrombus Healing to Underlying Plaque Morphology in Sudden Coronary Death

Miranda C.A. Kramer, MD^_*, Saskia Z.H. Rittersma, MD, PhD^_*, Robbert J. de Winter, MD, PhD^_*, Elena R. Ladich, MD, David R. Fowler, MD, You-Hui Liang, MD, Robert Kutys, MS, PA, Naima Carter-Monroe, MD, Frank D. Kolodgie, PhD, Allard C. van der Wal, MD, PhD and Renu Virmani, MD^,_*

^_* Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
CVPath Institute, Gaithersburg, Maryland
Department of Pathology, University of Maryland, Baltimore, Maryland

Manuscript received July 30, 2009; revised manuscript received September 3, 2009, accepted September 7, 2009.

^_* Reprint requests and correspondence: Dr. Renu Virmani, Medical Director, President, CVPath Institute, 19 Firstfield Road, Gaithersburg, Maryland 20878 (Email: rvirmani{at}cvpath.org).

Objectives: The aim of this study was to assess differences in thrombus healing between ruptured and eroded plaques, given the natural difference in lesion substrate and that thrombi might exist days to weeks before the presentation of sudden coronary death.

Background: Although the ability to distinguish ruptures and erosions remains a major clinical challenge, in-hospital patients dying with acute myocardial infarction establish that erosions account for 25% of all deaths, where women experience a higher incidence compared with men.

Methods: Coronary lesions with thrombi (ruptures, n = 65; erosions, n = 50) received in consultation from the Medical Examiner's Office from 111 sudden death victims were studied. Thrombus healing was classified as early (<1 day) or late stage characterized in phases of lytic (1 to 3 days), infiltrating (4 to 7 days), or healing (>7 days). Morphometric analysis included vessel dimensions, necrotic core size, and macrophage density.

Results: Late-stage thrombi were identified in 79 of 115 (69%) culprit plaques. Women more frequently had erosion with a greater prevalence of late-stage thrombi (44 of 50, 88%) than ruptures (35 of 65, 54%, p < 0.0001). The internal elastic lamina area and percent stenosis were significantly smaller in erosions compared with ruptures (p < 0.0001 and p = 0.02), where plaque burden was greater (p = 0.008). Although macrophage infiltration in erosions was significantly less than ruptures (p = 0.03), there was no established relationship with thrombus organization. Other parameters of thrombus length and occlusive versus nonocclusive showed no association with healing.

Conclusions: Approximately two-thirds of coronary thrombi in sudden coronary deaths are organizing, particularly in young individuals—especially women, who perhaps might require a different strategy of treatment.

Key Words: erosion • pathology • sudden coronary death • thrombosis • women

Abbreviations and Acronyms   AMI = acute myocardial infarction   H&E = hematoxylin and eosin (staining)   IEL = internal elastic lamina   LAD = left anterior descending coronary artery   LCx = left circumflex coronary artery   MI = myocardial infarction   PCI = percutaneous coronary intervention   RCA = right coronary artery   SCD = sudden coronary death   SMC = smooth muscle cell   STEMI = ST-segment elevation myocardial infarction