Coronary artery fixation at iso-arterial pressure: impacts on histologic evaluation and clinical management

Highlights

• Quantitative histopathology of perfused coronary artery shows reduced stenosis.

• Perfused coronary artery shows stenosis comparable to angiography.

• Quantitative histopathology of non-perfused histopathology show increased stenosis.

Abstract

Coronary angiography is the standard imaging method for determining the site, extent, and severity of coronary artery disease. Several publications have reported discordance between the degree of coronary artery stenosis determined from post-mortem histologic evaluation and coronary angiography. While the 2-dimensional limitations of coronary angiography are well established, the determination of coronary stenosis based on histologic evaluation of passively fixed samples is also associated with significant biases. In this study, we used patients with chronic coronary artery disease to compare the stenosis severity estimates that were determined using the passive fixation method with those determined using the active fixation method. Our results showed a significant discrepancy between the stenosis in passively fixed coronary arteries when compared with coronary angiography in all major coronary vessels combined (P=.002), and in Cx (P=.045) and CD (P=.026). However, there was no mean difference when compared with perfused (actively fixed) samples when all vessels were combined or examined individually. Iso-physiologic mechanical perfusion (active) fixation yielded significantly reduced coronary artery stenosis means when compared to the passive fixation method in post-mortem evaluations during autopsies. This was evident when all vessels were combined (P=.0001) and assessed individually (Cx (P=.003), LAD (P=.025), LM (P=.056) and RC (P=.007)). Autopsies including cardiac explant patients also showed differences in estimates for all vessels combined (P=.0001) and in Cx (P=.016) and RC (P=.006). In summary, our quantitative histopathology analyses using perfused coronary artery stenosis at physiologic pressure showed significant discrepancies when compared with passive histopathology.

Introduction

Chronic coronary artery disease (CAD) may lead to myocardial ischemia, which is one of the leading causes of mortality in industrialized countries [1], accounting for 7.6 million annual deaths worldwide [2]. It is widely recognized that 75% stenosis in the lumen cross-sectional area (LCSA) is sufficient to reduce the coronary arterial flow that is necessary to meet the myocardial oxygen demands during times of stress and exertion, while a narrowing of 90% causes ischemia at rest [3]. Forensic pathologists consider LCSA stenosis of 75% in at least one major coronary artery to be a sufficient explanatory factor in determining the cause of death of a patient [3], [4], [5].

Coronary angiography (CAG) is still the most widely used method for determining the site, extent and severity of CAD in clinical settings, and is common practice particularly during the preoperative work-up of cardiac surgery patients [6], [7]. Although invasive, this procedure is often relied upon to evaluate patient prognosis and eligibility for surgical procedures, and to guide clinical management and administer treatment, especially since the advent of myocardial revascularization techniques such as percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) [6], [8]. As the degree of stenosis bears such important implications for symptomatology correlation, prognosis prediction, clinical decision-making, treatment options and the determination of cause of death, it is evident that quantification methods should reflect the real “state” of stenosis associated with CAD as much as possible. Moreover, despite significant improvements in imaging techniques since the 1990s, discrepancies between CAG and histopathology are still observed in modern clinical settings [9], [10], [11].

Previous studies have reported substantial discordances when comparing the percentage of coronary artery stenosis determined from quantitative histologic methods to the percentage determined using CAG [6]. In fact, several investigators have reported findings of abnormal coronary arteries that were not visible using CAG, yet were well-established post-operatively or during autopsies [6]. These discrepancies have been a source of concern for cardiac surgeons and cardiologists as they may lead to an inaccurate assessment of a patient's cardiac state before they undergo a surgical procedure. This can have health implications for the patient as well as potential legal implications for the clinician.

Studies have shown that CAG also tends to underestimate the degree of coronary stenosis in comparison to pathological examinations [9], [10], [12], [13], [14], [15], [16]. Conversely, histopathology assessments tend to overestimate the percentage of stenosis, due to the relaxed and undistended state in which coronary arteries are traditionally fixed and examined, but also because pathologists estimate the severity of CAD by examining the internal elastic layer which is not possible through CAG [6].

In this project, we evaluated the impact of passive histopathological fixation (PHP) in the context of post-mortem and post-surgical histopathology analyses of coronary artery stenosis in patients with chronic CAD. We then compared the level of coronary artery stenosis determined using active histopathological fixation (AHP) as opposed to PHP. Finally, we assessed the effect of using AHP compared to in vivo coronary artery stenosis evaluation by CAG.