Virmani R

Pathologic assessment of the vulnerable human coronary plaque

Despite significant strides towards an understanding of the initiation and progression of atherosclerosis and the influence of risk factors, coronary heart disease remains the principal killer in the western world.1 If progress in the field is to continue in the 21st century, one must focus on high risk patients with lesions that are vulnerable to thrombosis together with the triggering mechanisms that cause plaques to rupture at a precise location and time. Although animal studies have helped define the molecular mechanisms of atherosclerosis, a convincing model of plaque rupture still does not exist. Therefore, the development of future treatments targeted against plaque instability is contingent upon our ability to confidently recognise precursor lesions likely to thrombose; this will be primarily achieved via improved imaging modalities. Insights into the mechanisms of coronary thrombosis extend from detailed analyses of underlying plaque morphologies in necropsy specimens from sudden death victims.2,3 In 50–75% of these cases, the culprit lesion (fatal plaque) shows a coronary thrombus whereas the remainder without thrombi exhibit stable coronary plaques with > 75% cross sectional area luminal narrowing.4 The major cause of acute coronary thrombosis is plaque rupture, and the precursor lesion has been termed vulnerable plaque (fig 1) or, as defined by our laboratory, the thin cap fibroatheroma (TCFA). In this review, we will critically analyse the pathology of plaque rupture with emphasis on its relation to TCFAs and healed plaque ruptures to gain a better understanding of the lesion most responsible for coronary morbidity and mortality. Figure 1  A non-haemodynamically limiting thin cap fibroatheroma. (A) Low power view of a thin cap fibroatheroma (TCFA) with a relatively large eccentric necrotic core (NC) and an overlying thin fibrous cap (< 65 μm); the greyish material in the lumen is barium gelatin (Movat pentachrome, ×20). (B) Image of …

Drug eluting stents: are human and animal studies comparable?

Animal models of stenting probably predict human responses as the stages of healing are remarkably similar. What is characteristically different is the temporal response to healing, which is substantially prolonged in humans. The prevention of restenosis in recent clinical trials of drug eluting stents may represent a near absent or incomplete phase of intimal healing. Continued long term follow up of patients with drug eluting stents for major adverse cardiac events and angiographic restenosis is therefore imperative.

Identification of Intraplaque Hemorrhage on MR Angiography Images: A Comparison of Contrast-Enhanced Mask and Time-of- Flight Techniques

BACKGROUND AND PURPOSE: MRA is widely used to measure carotid narrowing. Standard CE- and TOF-MRA techniques use highly T1-weighted gradient-echo sequences that can detect T1 short blood products, so they have the potential to identify IPH, an indicator of plaque rupture. We sought to determine the accuracy and reliability of these MRA sequences to detect IPH. MATERIALS AND METHODS: 3D TOF and CE carotid MRA scans were obtained at 3T on 15 patients (age range, 58–86 years; 13 men) scheduled for CEA. The source images from the precontrast (mask) CE-MRA and the TOF sequences were reviewed by 2 independent readers for IPH presence (identified as hyperintense signal intensity compared with adjacent muscle). CEA specimens were stained with antibody against glycophorin A and Mallory stain to detect IPH and were correlated with MR images. RESULTS: Nine of 15 CEA specimens (61 of 144 MR images) contained IPH confirmed by histology. Compared with TOF, CE-MRA mask demonstrated greater sensitivity, specificity, PPV, and NPV for IPH detection. The accuracy for correctly identifying IPH by using CE-MRA mask images and TOF images was 94% and 84%, respectively. Inter- and intraobserver agreement for IPH detection was excellent by mask images (κ = 0.91 and κ = 0.94, respectively) and TOF images (κ = 0.77 and κ = 0.84, respectively). CONCLUSIONS: CE-MRA mask images are highly accurate and reliable for identifying IPH, more so than the TOF sequence, and can potentially provide valuable information about risk for rupture.

Drug-eluting stent pathology--should we still be cautious?

The current FDA-approved drug-eluting stents (DESs; CYPHER® [Cordis, Miami Lakes, FL] and TAXUS® [Boston Scientific, Natick, MA]) have been associated with late stent thrombosis (LST; defined as thrombosis occurring >30 days following implantation). The mechanisms predictive of LST are, however, poorly understood. While CYPHER® and TAXUS® stents use different drug coatings, both effectively reduce restenosis. Pathologic studies are the best methods for detailed analysis of morphologic changes that occur following placement of DESs. We initially reported that both CYPHER® and TAXUS® stents produce delayed arterial healing evidenced by incomplete endothelialization and persistent fibrin deposition when compared with baremetal stents (BMSs) of similar implant duration. Several pathologic risk factors were identified, and later we reported that lack of endothelial strut coverage was the best single correlate of thrombosis. We also observed heterogeneity of healing in the stents with late thrombus. Underlying lesion anatomy and plaque morphology are important but frequently overlooked factors that can influence healing following DES implantation. In our own pathologic series, the incidence of stent thrombosis in bifurcation DES was higher than that for BMS for implants older than 30 days. These lesions also result in greater delayed arterial healing probably related to the flow disturbance at these locations. Healing is also affected by underlying plaque morphology, such as thin-cap fibroatheroma or ruptured plaques, which frequently underlie acute myocardial infarction (AMI). Stent strut penetration of the necrotic core is commonly observed at autopsy. Our pathologic studies have revealed a significantly higher incidence of LST in patients with AMI than in patients with stable plaque following DES implantation. We have also observed greater and more-uniform arterial healing in patients with stable lesions (i.e. fibroatheroma with or without calcification) than in AMI patients, emphasizing the importance of patient selection. Although two pivotal studies showed similar rates of stent thrombosis in AMI patients treated with DESs versus BMSs, the limited duration of follow-up (i.e. 1 year) precludes any definitive conclusion about the safety of this practice as most of these patients are receiving long-term antiplatelet therapy. A more recent clinical study has demonstrated that AMI is an independent risk factor for LST and associated with raised mortality risk. Given these findings, bifurcation and AMI stenting should be avoided to minimize the risk of LST with DESs. As the time course of complete healing with DES is unknown, the optimum duration of antiplatelet treatment remains to be determined. Even so, some cases of very LST (i.e. beyond 1 year) have been reported despite antiplatelet therapy, emphasizing the complexity of this issue. Clinicians must, therefore, concentrate on minimizing risk, which includes being aware of the anatomic features associated with greater risk of LST. Another complication reported in patients with DES is a localized hypersensitivity reaction in the underlying coronary artery. Our observations indicate that this phenomenon is limited to the use of the CYPHER® stent. Conversely, extensive fibrin deposition with or without stent malapposition is a more frequent finding with the TAXUS® stent. Hypersensitivity to CYPHER® stents invariably results in LST, whereas excessive fibrin deposition may or may not be associated with LST. The specific drugs and polymers used are likely to be responsible for these adverse reactions. DESs are a major innovation in interventional cardiology. We have no doubt that DESs are an effective treatment for the prevention of restenosis and can be safely used when patients are properly selected. There is, however, room for improvement. Thus, with the next generation of DESs, greater attention will be given to strut thickness, polymer choice, drug dose, and release kinetics—all of which are currently being pursued vigorously. Drug-eluting stent pathology—should we still be cautious?

Total anomalous origin of the coronary circulation from the right pulmonary artery

Origin of both coronary arteries from a branch of the pulmonary artery is rare and has not been reported as a cause of sudden unexpected death. We report autopsy findings of a 14-day male infant in previously good health who died suddenly. From the proximal right pulmonary artery arose a single coronary artery, which branched into the right and left main coronary arteries. The right proximal coronary artery coursed between the aorta and pulmonary trunk, and the left main traveled along the anterior proximal aorta. The distal course of the coronary circulation was normal. There was concentric subendocardial healing myocardial infarction. No other congenital anomalies were identified. Total anomalous origin of the coronary arteries from the pulmonary trunk or artery should be considered in cases of sudden unexpected death in infants.

Mitral valve laceration and papillary muscle rupture secondary to percutaneous balloon aortic valvuloplasty

Abstract Percutaneous balloon aortic valvuloplasty (PBAV) has been used successfully as a palliative treatment in patients with critical aortic stenosis.1,2 These patients are often elderly and are not candidates for aortic valve replacement.3 Alternatively, PBAV has been used as a temporizing measure in patients with aortic stenosis and other medical conditions that need more urgent treatment.4 The procedure is typically performed by retrograde heart catheterization; however, anterograde transeptal PBAV has been reported, and may have a lower incidence of bleeding and arterial damage.5 This report describes mitral valve laceration and papillary muscle rupture associated with anterograde transeptal PBAV, a complication not previously reported.

The value of MRA images for identifying intraplaque hemorrhage in carotid plaque

Introduction MR angiography (MRA) has become a standard workup for carotid atherosclerosis, using either contrast-enhanced (CE) or time-of-flight (TOF) techniques. This provides a measure of narrowing but does not identify plaque components that indicate risk of rupture, such as the presence of intraplaque hemorrhage (IPH). CE and TOF techniques employ highly T1-weighted 3D gradient-echo sequences, and have the potential to detect IPH because of T1 short blood products.