H. Thomas Aretz

Characterization of Human Atherosclerosis by Optical Coherence Tomography

Background—High-resolution visualization of atherosclerotic plaque morphology may be essential for identifying coronary plaques that cause acute coronary events. Optical coherence tomography (OCT) is an intravascular imaging modality capable of providing cross-sectional images of tissue with a resolution of 10 &mgr;m. To date, OCT imaging has not been investigated in sufficient detail to assess its accuracy for characterizing atherosclerotic plaques. The aim of this study was to establish objective OCT image criteria for atherosclerotic plaque characterization in vitro. Methods and Results—OCT images of 357 (diseased) atherosclerotic arterial segments obtained at autopsy were correlated with histology. OCT image criteria for 3 types of plaque were formulated by analysis of a subset (n=50) of arterial segments. OCT images of fibrous plaques were characterized by homogeneous, signal-rich regions; fibrocalcific plaques by well-delineated, signal-poor regions with sharp borders; and lipid-rich plaques by signal-poor regions with diffuse borders. Independent validation of these criteria by 2 OCT readers for the remaining segments (n=307) demonstrated a sensitivity and specificity ranging from 71% to 79% and 97% to 98% for fibrous plaques, 95% to 96% and 97% for fibrocalcific plaques, and 90% to 94% and 90% to 92% for lipid-rich plaques, respectively (overall agreement, &kgr;=0.83 to 0.84). The interobserver and intraobserver reliabilities of OCT assessment were high (&kgr; values of 0.88 and 0.91, respectively). Conclusions—Objective OCT criteria are highly sensitive and specific for characterizing different types of atherosclerotic plaques. These results represent an important step in validating this new intravascular imaging modality and will provide a basis for the interpretation of intracoronary OCT images obtained from patients.

Visualization of Coronary Atherosclerotic Plaques in Patients Using Optical Coherence Tomography: Comparison With Intravascular Ultrasound

OBJECTIVES The aim of this study was to evaluate the feasibility and the ability of intravascular optical coherence tomography (OCT) to visualize the components of coronary plaques in living patients. BACKGROUND Disruption of a vulnerable coronary plaque with subsequent thrombosis is currently recognized as the primary mechanism for acute myocardial infarction. Although such plaques are considered to have a thin fibrous cap overlying a lipid pool, imaging modalities in current clinical practice do not have sufficient resolution to identify thin (< 65 microm) fibrous caps. Optical coherence tomography is a new imaging modality capable of obtaining cross-sectional images of coronary vessels at a resolution of approximately 10 microm. METHODS The OCT images and corresponding histology of 42 coronary plaques were compared to establish OCT criteria for different types of plaques. Atherosclerotic lesions with mild to moderate stenosis were identified on angiograms in 10 patients undergoing cardiac catheterization. Optical coherence tomography and intravascular ultrasound (IVUS) images of these sites were obtained in all patients without complication. RESULTS Comparison between OCT and histology demonstrated that lipid-rich plaques and fibrous plaques have distinct OCT characteristics. A total of 17 IVUS and OCT image pairs obtained from patients were compared. Axial resolution measured 13 +/- 3 microm with OCT and 98 +/- 19 microm with IVUS. All fibrous plaques, macrocalcifications and echolucent regions identified by IVUS were visualized in corresponding OCT images. Intimal hyperplasia and echolucent regions, which may correspond to lipid pools, were identified more frequently by OCT than by IVUS. CONCLUSIONS Intracoronary OCT appears to be feasible and safe. Optical coherence tomography identified most architectural features detected by IVUS and may provide additional detailed structural information.

In Vivo Characterization of Coronary Atherosclerotic Plaque by Use of Optical Coherence Tomography

Background—The current understanding of the pathophysiology of coronary artery disease is based largely on postmortem studies. Optical coherence tomography (OCT) is a high-resolution (≈10 μm), catheter-based imaging modality capable of investigating detailed coronary plaque morphology in vivo. Methods and Results—Patients undergoing cardiac catheterization were enrolled and categorized according to their clinical presentation: recent acute myocardial infarction (AMI), acute coronary syndromes (ACS) constituting non–ST-segment elevation AMI and unstable angina, or stable angina pectoris (SAP). OCT imaging was performed with a 3.2F catheter. Two observers independently analyzed the images using the previously validated criteria for plaque characterization. Of 69 patients enrolled, 57 patients (20 with AMI, 20 with ACS, and 17 with SAP) had analyzable images. In the AMI, ACS, and SAP groups, lipid-rich plaque (defined by lipid occupying ≥2 quadrants of the cross-sectional area) was observed in 90%, 75%, and 59%, respectively (P=0.09). The median value of the minimum thickness of the fibrous cap was 47.0, 53.8, and 102.6 μm, respectively (P=0.034). The frequency of thin-cap fibroatheroma (defined by lipid-rich plaque with cap thickness ≤65 μm) was 72% in the AMI group, 50% in the ACS group, and 20% in the SAP group (P=0.012). No procedure-related complications occurred. Conclusions—OCT is a safe and effective modality for characterizing coronary atherosclerotic plaques in vivo. Thin-cap fibroatheroma was more frequently observed in patients with AMI or ACS than SAP. This is the first study to compare detailed in vivo plaque morphology in patients with different clinical presentations.

Quantification of Macrophage Content in Atherosclerotic Plaques by Optical Coherence Tomography

Background—Macrophage degradation of fibrous cap matrix is an important contributor to atherosclerotic plaque instability. An imaging technology capable of identifying macrophages in patients could provide valuable information for assessing plaque vulnerability. Optical coherence tomography (OCT) is a new intravascular imaging modality that allows cross-sectional imaging of tissue with a resolution of ≈10 &mgr;m. The aim of this study was to investigate the use of OCT for identifying macrophages in fibrous caps. Methods and Results—OCT images of 26 lipid-rich atherosclerotic arterial segments obtained at autopsy were correlated with histology. Cap macrophage density was quantified morphometrically by immunoperoxidase staining with CD68 and smooth muscle actin and compared with the standard deviation of the OCT signal intensity at corresponding locations. There was a high degree of positive correlation between OCT and histological measurements of fibrous cap macrophage density (r =0.84, P <0.0001) and a negative correlation between OCT and histological measurements of smooth muscle actin density (r =−0.56, P <0.005). A range of OCT signal standard deviation thresholds (6.15% to 6.35%) yielded 100% sensitivity and specificity for identifying caps containing >10% CD68 staining. Conclusions—The high contrast and resolution of OCT enables the quantification of macrophages within fibrous caps. The unique capabilities of OCT for fibrous cap characterization suggest that this technology may be well suited for identifying vulnerable plaques in patients.

Active myocarditis in the spectrum of acute dilated cardiomyopathies: clinical features, histologic correlates, and clinical outcome

We studied the clinical features and course (average follow-up time, 18 months) of 27 patients with acute dilated cardiomyopathy (symptoms for less than 6 months) who were referred for endomyocardial biopsy. Almost 40 per cent of the patients subsequently had a rise in left ventricular ejection fraction (on average, from 0.21 to 0.41) and substantial improvement in heart failure; the remainder died or had chronic dilated cardiomyopathy. Biopsy revealed myocarditis in 18 patients, and this finding was especially common (89 per cent) in patients who had been ill for less than four weeks. But the biopsy specimen was negative in four patients whose clinical features and later course were diagnostic of myocarditis. Nine patients received immunosuppressive drugs, and four improved--a rate that did not differ from the rate of spontaneous improvement. Neither the histologic features of the biopsy specimen nor the clinical features at presentation were clearly correlated with subsequent improvement, whether or not immunosuppressive drugs were given. We conclude that many cases of unexplained dilated cardiomyopathy result from myocarditis. Definitive histologic confirmation depends on the duration of illness. The efficacy of immunosuppressive treatment must still be established.

Effect of antireflux operation on Barrett's mucosa

Regression of Barretts epithelium after antireflux operations remains a controversial topic. We evaluated the effect of antireflux procedures in patients with Barretts esophagus on the regression of columnar epithelium and dysplasia and its potential protective effect on the subsequent development of carcinoma. Of the 241 patients with Barretts esophagus treated at the Lahey Clinic from 1973 to 1989, 37 patients underwent an antireflux operation. Regression was defined as histological evidence of regenerating squamous mucosa that completely or partially replaced the columnar epithelium. Improvement in lower esophageal sphincter pressure to 12 mm Hg or greater occurred in 19 of 26 patients (73%) who had perioperative manometry. Symptomatic relief of esophagitis occurred in 34 of 37 patients (92%). Four patients had partial regression with regenerating squamous mucosa juxtaposed with areas of columnar epithelium. Carcinoma developed in 3 of 37 patients (8.1%). One patient had recurrence of severe symptoms of reflux esophagitis before development of carcinoma. Patients with Barretts esophagus who have undergone a successful antireflux operation with symptomatic relief and evidence of improvement in lower esophageal sphincter pressures rarely show regression of Barretts mucosa and may still be at risk for development of carcinoma. Therefore, the indications for antireflux operation in Barretts esophagus should remain the same as for other patients with gastroesophageal reflux, but yearly endoscopic and histological surveillance should be continued postoperatively.

Porcine coronary imaging in vivo by optical coherence tomography.

OBJECTIVE A high-resolution coronary artery imaging modality has the potential to address important diagnostic and management problems in cardiology. Optical coherence tomography (OCT) is a promising new optical imaging technique with a resolution of approximately 10 microm. The purpose of this study was to use a new OCT catheter to demonstrate the feasibility of performing OCT imaging of normal coronary arteries, intimal dissections, and deployed stents in vivo. METHODS AND RESULTS Normal coronary arteries, intimal dissections, and stents were imaged in five swine with OCT and compared with intravascular ultrasound (IVUS). In the normal coronary arteries, visualization of all of the layers of the vessel wall was achieved with a saline flush, including the intima which was not identified by IVUS. Following dissection, detailed layered structures including intimal flaps, intimal defects, and disruption of the medial wall were visualized by OCT. IVUS failed to show clear evidence of intimal and medial disruption. Finally, the microanatomic relationships between stents and the vessel walls were clearly identified only by OCT. CONCLUSIONS In this preliminary experiment, we have demonstrated that in vivo OCT imaging of normal coronary arteries, intimal dissections, and deployed stents is feasible, and allows identification of clinically relevant coronary artery morphology with high-resolution and contrast.

Morphology of atrial myocardium in human pulmonary veins: A postmortem analysis in patients with and without atrial fibrillation

OBJECTIVES We report an in-depth postmortem morphologic analysis of atrial myocardium in human pulmonary veins (PVs) from patients with and without atrial fibrillation (AF). BACKGROUND Electrophysiologic studies established the critical role of PVs in the initiation of AF. To date, a paucity of data exists about PV morphology as an arrhythmogenic substrate. METHODS Longitudinal tissue-strips of PVs were excised and histologically analyzed from the distal part to just beyond the atriovenous junction in the left atrium from 20 patients, obtained at autopsy. Anatomical measurements, including diameters, lengths, and wall-thicknesses of PVs, obtained at autopsy, were made. RESULTS Histological analysis revealed extension of atrial myocardium into 89% of all PVs. Prevalence of myocardial extension was significantly higher in veins of 6 patients with compared with 14 patients without AF. Other significant differences in the histology of PVs between the two groups were a higher frequency of discontinuity and hypertrophy and a higher degree of fibrosis of the atrial myocardium in the PVs of patients with AF. A marked variation existed in anatomical dimensions of PVs, although no differences were observed between patients with or without AF. CONCLUSIONS Atrial myocardium was more often present in the PVs of patients with compared with patients without AF. In the first group, the atrial myocardium in the PVs was characterized by more severe discontinuity, hypertrophy, and fibrosis. A marked variation in anatomical dimensions of the PVs existed.

Transurethral ultrasound-guided laser-induced prostatectomy (tulip procedure) : a canine prostate feasibility study

We describe the TULIP procedure, a new system to relieve bladder outlet obstruction caused by benign prostatic hyperplasia. This device is composed of a real-time 7.5 MHz ultrasound transducer coupled to a Nd:YAG laser with a 1.064 microns wavelength that fires through an intact intraprostatic balloon. A series of feasibility studies in 21 canine prostate glands was performed with a follow-up time to 3 months. Results indicate that the Nd:YAG laser in the 20 to 40 W range at a pull rate of approximately 1 mm. per second is an effective means of removing substantial amounts of canine benign prostatic hyperplasia. Transurethral ultrasonography was a reliable means of identifying essential landmarks and of controlling the laser. Prostatectomy by laser coagulation necrosis resulted in no bleeding or postoperative obstruction. Intraoperative irrigation fluids were not required, eliminating systemic volume related problems.

Acute pancreatitis after cardiopulmonary bypass

We have described a spectrum of pancreatic surgery after cardiopulmonary bypass. At one end is a subclinical lesion which was manifested only by elevations in serum isoamylase levels (27 percent of patients) and increased ribonuclease levels (13 percent of patients) in asymptomatic patients followed after cardiac surgery. At the other end is a severe and often lethal necrotizing pancreatitis. Acute necrotizing pancreatitis was found at autopsy in 25 percent of 138 patients who died after cardiac surgery, and it correlated strongly with low output, acute tubular necrosis, and infarction of the liver, spleen, or bowel. It was the principal cause of death in 4 percent of these patients. In addition, 24 percent of 38 nonsurgical patients who died from cardiac failure and hypoperfusion had acute pancreatitis at autopsy, whereas acute pancreatitis was not observed in 55 nonsurgical patients who died without a significant period of low output. Acute pancreatitis was recognized postoperatively in 12 patients (0.2 percent). Three had mild pancreatitis, and all responded well to conservative therapy. In nine patients, fulminant necrotizing pancreatitis developed. Their courses were characterized by significant early postoperative hemodynamic compromise, abdominal distention, ileus, fever, and episodes of late vascular instability associated with hypocalcemia. The diagnosis of pancreatitis was usually missed because of the absence of pain, tenderness and hyperamylasemia. The diagnosis was confirmed at laparotomy in eight patients and at autopsy in one. The only two survivors among the nine with severe cases had aggressive mobilization, debridement, and wide drainage of the necrotic pancreas. We suggest that a mild subclinical injury to the pancreas may occur as a consequence of cardiopulmonary bypass and may progress to severe ischemic necrosis if hypoperfusion follows in the postoperative period, the presentation of necrotizing pancreatitis may be atypical in the cardiac surgical patient and should be considered if nonspecific abdominal symptoms are present, and aggressive debridement and drainage may be the optimal treatment for aggressive forms of this disease.