Sergio Waxman

Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation.

OBJECTIVES The purpose of this document is to make the output of the International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT) Standardization and Validation available to medical and scientific communities, through a peer-reviewed publication, in the interest of improving the diagnosis and treatment of patients with atherosclerosis, including coronary artery disease. BACKGROUND Intravascular optical coherence tomography (IVOCT) is a catheter-based modality that acquires images at a resolution of ~10 μm, enabling visualization of blood vessel wall microstructure in vivo at an unprecedented level of detail. IVOCT devices are now commercially available worldwide, there is an active user base, and the interest in using this technology is growing. Incorporation of IVOCT in research and daily clinical practice can be facilitated by the development of uniform terminology and consensus-based standards on use of the technology, interpretation of the images, and reporting of IVOCT results. METHODS The IWG-IVOCT, comprising more than 260 academic and industry members from Asia, Europe, and the United States, formed in 2008 and convened on the topic of IVOCT standardization through a series of 9 national and international meetings. RESULTS Knowledge and recommendations from this group on key areas within the IVOCT field were assembled to generate this consensus document, authored by the Writing Committee, composed of academicians who have participated in meetings and/or writing of the text. CONCLUSIONS This document may be broadly used as a standard reference regarding the current state of the IVOCT imaging modality, intended for researchers and clinicians who use IVOCT and analyze IVOCT data.

Three-Dimensional Coronary Artery Microscopy by Intracoronary Optical Frequency Domain Imaging

OBJECTIVES We present the first clinical experience with intracoronary optical frequency domain imaging (OFDI) in human patients. BACKGROUND Intracoronary optical coherence tomography (OCT) is a catheter-based optical imaging modality that is capable of providing microscopic (approximately 7-microm axial resolution, approximately 30-microm transverse resolution), cross-sectional images of the coronary wall. Although the use of OCT has shown substantial promise for imaging coronary microstructure, blood attenuates the OCT signal, necessitating prolonged, proximal occlusion to screen long arterial segments. OFDI is a second-generation form of OCT that is capable of acquiring images at much higher frame rates. The increased speed of OFDI enables rapid, 3-dimensional imaging of long coronary segments after a brief, nonocclusive saline purge. METHODS Volumetric OFDI images were obtained in 3 patients after intracoronary stent deployment. Imaging was performed in the left anterior descending and right coronary arteries with the use of a nonocclusive saline purge rates ranging from 3 to 4 ml/s and for purge durations of 3 to 4 s. After imaging, the OFDI datasets were segmented using previously documented criteria and volume rendered. RESULTS Good visualization of the artery wall was obtained in all cases, with clear viewing lengths ranging from 3.0 to 7.0 cm at pullback rates ranging from 5 to 20 mm/s. A diverse range of microscopic features were identified in 2 and 3 dimensions, including thin-capped fibroatheromas, calcium, macrophages, cholesterol crystals, bare stent struts, and stents with neointimal hyperplasia. There were no complications of the OFDI procedure. CONCLUSIONS Our results demonstrate that OFDI is a viable method for imaging the microstructure of long coronary segments in patients. Given its ability to provide microscopic information in a practical manner, this technology may be useful for studying human coronary pathophysiology in vivo and as a clinical tool for guiding the management of coronary artery disease.

In vivo validation of a catheter-based near-infrared spectroscopy system for detection of lipid core coronary plaques: initial results of the SPECTACL study.

OBJECTIVES To determine whether catheter-based near-infrared spectroscopy (NIRS) signals obtained with a novel catheter-based system from coronaries of patients are similar to those from autopsy specimens and to assess initial safety of NIRS device. BACKGROUND An intravascular NIRS system for detection of lipid core-containing plaques (LCP) has been validated in human coronary autopsy specimens. The SPECTACL (SPECTroscopic Assessment of Coronary Lipid) trial was a parallel first-in-human multicenter study designed to demonstrate the applicability of the LCP detection algorithm in living patients. METHODS Intracoronary NIRS was performed in patients undergoing percutaneous coronary intervention. Acquired spectra were blindly compared with autopsy NIRS signals with multivariate statistics. To meet the end point of spectral similarity, at least two-thirds of the scans were required to have >80% of spectra similar to the autopsy spectra. RESULTS A total of 106 patients were enrolled; there were no serious adverse events attributed to NIRS. Spectroscopic data could not be obtained in 17 (16%) patients due to technical limitations, leaving 89 patients for analysis. Spectra from 30 patients were unblinded to test the calibration of the LCP detection algorithm. Of the remaining 59 blinded cases, after excluding 11 due to inadequate data, spectral similarity was demonstrated in 40 of 48 spectrally adequate scans (83% success rate, 95% confidence interval: 70% to 93%, median spectral similarity/pullback: 96%, interquartile range 10%). The LCP was detected in 58% of 60 spectrally similar scans from both cohorts. CONCLUSIONS This intravascular NIRS system safely obtained spectral data in patients that were similar to those from autopsy specimens. These results demonstrate the feasibility of invasive detection of coronary LCP with this novel system. (SPECTACL: SPECTroscopic Assessment of Coronary Lipid; NCT00330928).

Detection and treatment of vulnerable plaques and vulnerable patients: novel approaches to prevention of coronary events.

There is growing interest in the possibility that identification and treatment of vulnerable plaques and vulnerable patients can enhance the progress made against coronary artery disease. Innovations in medical therapy—statins and other agents—and novel interventional cardiology techniques—eg, drug-eluting stents—have significantly decreased the morbidity and mortality caused by coronary atherosclerosis. However, coronary events continue to be the leading cause of death in the United States, accounting for >479 000 deaths (1 in 5) in 2003.1 Improved preventive measures are needed because, for many individuals, sudden coronary death is the first sign of the disorder. And even those who survive an acute coronary syndrome remain at high risk. After successful treatment of the initial culprit lesion by a percutaneous coronary intervention (PCI), the risk of a coronary event from a new lesion is ≈10% in the following year and 5% in each of the subsequent 4 years2,3 (Figure 1). Figure 1. Occurrence of coronary events (revascularization, death, MI, acute coronary syndromes, or congestive heart failure) after PCI in 4 studies of bare-metal stents. In addition to events resulting from stented lesions (solid line), many events are caused by nontarget (vulnerable) plaques (dashed line). Modified from Cutlip et al2 with permission from the American Heart Association. Copyright 2004. These substantial levels of ongoing morbidity and mortality have led to heightened interest in new methods to prevent coronary events. For primary prevention, the effort has focused on plasma markers and noninvasive testing to identify vulnerable individuals. For secondary prevention, interest has focused on vulnerable patients and the vulnerable plaques they may possess that might be identified and treated during the catheterization for their initial event. ### Definitions of the Vulnerable Plaque and the Vulnerable Patient The terminology to describe vulnerability has become relatively standardized.4–10 The term “vulnerable plaque” is used to designate a plaque at high risk of disruption leading …

Detection of high-risk atherosclerotic plaque: report of the NHLBI Working Group on current status and future directions.

The leading cause of major morbidity and mortality in most countries around the world is atherosclerotic cardiovascular disease, most commonly caused by thrombotic occlusion of a high-risk coronary plaque resulting in myocardial infarction or cardiac death, or embolization from a high-risk carotid plaque resulting in stroke. The lesions prone to result in such clinical events are termed vulnerable or high-risk plaques, and their identification may lead to the development of pharmacological and mechanical intervention strategies to prevent such events. Autopsy studies from patients dying of acute myocardial infarction or sudden death have shown that such events typically arise from specific types of atherosclerotic plaques, most commonly the thin-cap fibroatheroma. However, the search in human beings for vulnerable plaques before their becoming symptomatic has been elusive. Recently, the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study demonstrated that coronary plaques that are likely to cause future cardiac events, regardless of angiographic severity, are characterized by large plaque burden and small lumen area and/or are thin-cap fibroatheromas verified by radiofrequency intravascular ultrasound imaging. This study opened the door to identifying additional invasive and noninvasive imaging modalities that may improve detection of high-risk atherosclerotic lesions and patients. Beyond classic risk factors, novel biomarkers and genetic profiling may identify those patients in whom noninvasive imaging for vulnerable plaque screening, followed by invasive imaging for risk confirmation is warranted, and in whom future pharmacological and/or device-based focal or regional therapies may be applied to improve long-term prognosis.

Late coronary stent thrombosis: Early vs. late stent thrombosis in the stent era

The incidence of coronary stent thrombosis is < 1%–2% in recent studies, with the highest‐risk period considered to be the first 30 days following stent implantation. Recently, stent thrombosis after 30 days has been reported in patients undergoing brachytherapy with stenting. We reviewed the incidence of stent thrombosis causing myocardial infarction in nonbrachytherapy patients at our institution between 1 January 1996 and 30 November 1999. A case control methodology was employed with a 1:3 ratio of stent thrombosis to control patients. Of 1,191 patients undergoing coronary stenting, acute (< 24 hr) plus subacute (1–30 days) stent thrombosis occurred in 0.92% (11 of 1,191 patients). A further 0.76% (9 of 1,191 patients) developed late stent thrombosis after 30 days. There were no clinical or angiographic features at the time of the initial procedure that were associated with stent thrombosis as an entire group compared with control group, but early (acute and subacute) stent thrombosis patients had a smaller final stent minimal lumen diameter and longer stent length compared with patients who had late stent thrombosis or controls. Late stent thrombosis occurs in nonbrachytherapy patients and is almost as frequent as early stent thrombosis. Further studies are required to determine whether longer‐term poststent pharmacological treatment may decrease or prevent this complication. Cathet Cardiovasc Intervent 2002;55:142–147.

Clinical Characteristics of Tako-Tsubo Cardiomyopathy

Tako-tsubo cardiomyopathy (TTC) is increasingly diagnosed in the United States, especially in the Caucasian population. To evaluate the clinical features and outcome of patients with TTC, we evaluated 34 patients (32 women and 2 men) 22 to 88 years of age (mean 66 +/- 14) who fulfilled the following criteria: (1) akinesia or dyskinesia of the apical and/or midventricular segments of the left ventricle with regional wall motion abnormalities that extended beyond the distribution of a single epicardial vessel and (2) absence of obstructive coronary artery disease. Twenty-five patients (74%) presented with chest pain, 20 patients (59%) presented with dyspnea, and 8 patients (24%) presented with cardiogenic shock. Twenty-two patients (65%) had ST-segment elevation and 14 patients (41%) had T-wave inversion on presentation. Twenty-five patients (74%) reported a preceding stressful event. Cardiac biomarkers were often mildly increased, with a mean troponin I (peak) of 13.9 +/- 24. Mean +/- SD left ventricular ejection fractions were 28 +/- 10% at time of presentation and 51 +/- 14 at time of follow-up (p <0.0001). Two patients (6%) died during the hospital stay. Average duration of hospital stay was 6.6 +/- 6.2 days. In conclusion, TTC is common in postmenopausal women with preceding physical or emotional stress. It predominantly involves the apical portion of the left ventricle and patients with this condition have a favorable outcome with appropriate medical management. The precise cause remains unclear.

Angioscopic Predictors of Early Adverse Outcome After Coronary Angioplasty in Patients With Unstable Angina and Non–Q-Wave Myocardial Infarction

BACKGROUND Clinical and angiographic criteria have a limited ability to predict adverse outcome in patients with unstable angina who are undergoing percutaneous transluminal coronary angioplasty (PTCA). We investigated whether the use of angioscopy can improve prediction of early adverse outcome after PTCA. METHODS AND RESULTS Angioscopic characterization of the culprit lesion was performed before PTCA in 32 patients with unstable angina and 10 with non-Q-wave infarction. Seven patients (17%) had an adverse outcome (myocardial infarction, repeat PTCA, or need for coronary artery bypass graft surgery) within 24 hours after PTCA. Six of 18 patients with a yellow culprit lesion had an adverse outcome compared with 1 of 24 in whom the culprit lesion was white (P = .03). Six of 20 patients with plaque disruption suffered an adverse outcome compared with 1 of 22 with nondisrupted plaques (P = .04). Six of 17 patients with intraluminal thrombus had an adverse outcome, whereas only 1 of 25 patients without thrombus suffered an adverse outcome (P = .01). Yellow color, disruption, and thrombus at the culprit lesion site were associated with an eightfold increase in risk of adverse outcome after PTCA. The prediction of PTCA outcome based on characteristics of the plaque that were identifiable by angioscopy was superior to that estimated by the use of angiographic variables. CONCLUSIONS In patients with unstable angina and non-Q-wave infarction, angioscopic features of disruption, yellow color, or thrombus at the culprit lesion site can identify patients at high risk of early adverse outcome after PTCA. Angioscopy was superior to angiography for prediction of PTCA outcome.

Effect of autonomic nervous system dysfunction on the circadian pattern of myocardial ischemia in diabetes mellitus

OBJECTIVES The aim of this study was to determine the prevalence and characteristics of ambulatory myocardial ischemia in patients with diabetes mellitus and to delineate the relation between the presence and severity of autonomic nervous system dysfunction and the incidence and time of onset of myocardial ischemia. BACKGROUND Conflicting data exist with regard to the circadian pattern of myocardial infarction and other cardiovascular events, such as ambulatory ischemia, in diabetes. METHODS We performed ambulatory electrocardiographic monitoring in 60 patients with diabetes and coronary artery disease. Autonomic nervous system testing was performed in a subgroup of 25 patients with myocardial ischemia after discontinuation of all antianginal medications. RESULTS Thirty-eight of 60 patients had evidence of ambulatory ischemia; 91% of all ischemic episodes were asymptomatic. The 25 patients with ambulatory ischemia who underwent autonomic nervous system testing had a peak incidence of ischemia between 6 AM and noon (46 of 133 ischemic episodes, p < 0.007), compared with the other three 6-h periods. Fifteen of the 25 patients had no or mild autonomic nervous system dysfunction and demonstrated a similar peak incidence of ischemia between 6 AM and noon (p = 0.0009). However, the 10 patients with moderate to severe autonomic nervous system dysfunction did not experience a morning peak of ischemia, and the number of ischemic episodes was distributed evenly throughout the day (p = 0.4). CONCLUSIONS Silent ischemia is highly prevalent among patients with diabetes and coronary artery disease. Time of onset of ischemia in diabetic patients follows a circadian distribution, with a peak incidence in the morning hours. However, patients with significant autonomic nervous system dysfunction did not demonstrate such a peak, suggesting that alterations in sympathovagal balance may have an effect on the circadian pattern of cardiovascular events.

Transatrial Access to the Normal Pericardial Space A Novel Approach for Diagnostic Sampling, Pericardiocentesis, and Therapeutic Interventions

BACKGROUND A nonsurgical means to access the normal pericardial space could provide opportunities for diagnostic sampling and therapeutic interventions. Because there are currently no approved nonsurgical methods to accomplish this, we tested a new approach in large animals. METHODS AND RESULTS A catheter system was employed in a percutaneous approach from a femoral vein to pierce the right atrial appendage. Pericardial access was confirmed by placement of a radiopaque guidewire visible under fluoroscopy (6 dogs, 13 pigs). In 7 of the pigs, pericardial tamponade, produced by injection of saline or heparinized blood into the pericardial space through this route, was confirmed by fluoroscopy and hemodynamic evidence. The feasibility and safety of this access route were tested with multiple repetitions in all 19 animals. At the end of each of the 17 acute experiments, direct inspection after thoracotomy revealed no hemopericardium, laceration, or bleeding on catheter withdrawal. In 24-hour survival studies performed in 2 of the 6 dogs, the animals exhibited no behavioral signs of discomfort or untoward consequences on recovery from anesthesia. Histology revealed only a small (approximately 1-mm) fibrinous plug at the site of puncture. CONCLUSIONS The percutaneous approach via the right atrial appendage provides a rapid, safe route to access the normal pericardial space for diagnostic sampling and to alleviate high-volume and low-volume (<200 mL) pericardial effusions. The access route is potentially useful for selective administration of therapeutic agents, growth factors, gene vectors, and cardioactive and vasoactive agents to the heart.