Unstable Clinical Presentation Research Articles

Atraumatic rupture of the spleen caused by Plasmodium falciparum, challenge in UN peacekeeping operations - a case report

Introduction. Unlike traumatic rupture of the spleen, which is the most common consequence of blunt abdominal trauma and is well documented in the literature, and unlike the atraumatic rupture of the spleen, which is less common but al-so well described, spontaneous rupture of the spleen in a patient with malaria is a rare complication, with a potentially fatal outcome. Case report. A soldier aged 46 years, was hospitalized, with the clinical picture of abdominal colic and diarrhea, previously treated for a primary attack of acute malaria. During hospitalization, deterioration of health condition occurred, with the development of a clinical picture of an acute abdomen due to spontaneous rupture of the spleen which was successfully resolved by splenectomy. Conclusion. Splenectomy is the method of choice for patients with unstable clinical presentation due to atraumatic rupture of the spleen.

Ventricular Tachycardia.

This scenario was developed to educate emergency medicine residents on the diagnosis and management of ventricular tachycardia (VT) that is refractory to single dose anti-arrhythmic management. Electrical storm, defined as three or more episodes of sustained VT, ventricular fibrillation, or appropriate shocks from an implantable cardioverter defibrillator within 24 hours,1 has a mortality rate up to 14% in the first 48 hours.2 Ventricular tachycardia may present in a heterogenous fashion, not only with stable versus unstable clinical presentations, but also with different electrocardiographic morphologies and etiologies.1 Understanding how to rapidly diagnose, treat, and utilize second or third-line treatments is vital in the setting of refractory ventricular tachycardia rather than relying on the success of first-line agents. Appreciation for what medications are readily available in your crash cart and medication dispensing cabinet is critical for timely management for refractory ventricular tachycardia. At the conclusion of the simulation session, learners will be able to: 1) identify the different etiologies of VT, including structural heart disease, acute ischemia, and acquired or congenital QT syndrome; 2) describe confounding factors of VT, such as electrolyte abnormalities and sympathetic surge; 3) describe how to troubleshoot an unsuccessful synchronized cardioversion, including checking equipment connections, increasing delivered energy, and changing pad placement; 4) compare and contrast treatments of VT based on suspected underlying etiology; 5) describe reasons to activate the cardiac catheterization lab other than occlusive myocardial infarction; and 6) identify appropriate disposition of the patient to the cardiac catheterization lab. This session was conducted using high-fidelity simulation, followed by a debriefing session and lecture on the diagnosis, differential diagnosis, and management of VT. Debriefing methods may be left to the discretion of participants, but the authors have utilized advocacy-inquiry techniques. This scenario may also be run as an oral board case. Our residents are provided a survey at the completion of the debriefing session so they may rate different aspects of the simulation, as well as provide qualitative feedback on the scenario. The local institution's simulation center's electronic feedback form is based on the Center of Medical Simulation's Debriefing Assessment for Simulation in Healthcare (DASH) Student Version Short Form3 with the inclusion of required qualitative feedback if an element was scored less than a 6 or 7. Twelve learners completed a feedback form. This session received 6 and 7 scores (consistently effective/very good and extremely effective/outstanding, respectively) other than three isolated 5 scores. The lowest average score was 6.67 for "Before the simulation, the instructor set the stage for an engaging learning experience." The highest average score was 7 for "The instructor helped me see how to improve or how to sustain good performance." The form also includes an area for general feedback about the case at the end. Illustrative examples of feedback include: "Excellent care and debrief." Specific scores are available upon request. This is a cost-effective method for reviewing VT diagnosis and management. The case may be modified for appropriate audiences, such as describing what medications may be readily available in a free-standing emergency department or pre-hospital setting. Medical simulation, ventricular tachycardia, cardiac emergencies, dysrhythmias, cardiology, emergency medicine.

Acute ischemic events are frequent after primary coronary stenting.

The purpose of this study was to assess the incidence, predictors, and presentation of target vessel failure (TVF) after primary stenting for ST-segment elevation myocardial infarction (MI) as opposed to elective stenting. A total of 8237 consecutive patients undergoing urgent or elective percutaneous coronary intervention (PCI) were enrolled in our database and followed for a median of 1234 days (interquartile range 782-1688 days). Any acute ischemic event attributed to the obstruction of the stented vessel was considered as TVF. Stent thrombosis was classified according to the Academic Research Consortium, whereas restenosis and new culprit lesion were defined as obstructions within or outside stent boundaries, respectively. Unstable clinical presentation required urgent hospital admission or caused unexplained sudden death. Multivariable analyses were performed with Cox proportional hazards regression models. TVF occurred in 4.2% of our population. A measurable proportion of patients had to be re-admitted to hospital: 1.6% because of stent thrombosis, 1.5% because of restenosis, and 0.3% because of new culprit lesion. Ten (0.1%) patients were found victims of sudden death. De-novo lesions showed less TVF [hazard ratio (HR) 0.22, 95% confidence interval (CI) 0.16-0.30, P < 0.0001]. Primary PCI was associated with increased risk of TVF (HR 1.83, 95% CI 1.43-2.36, P < 0.0001), stent thrombosis (HR 2.59, 95% CI 1.80-3.72, P < 0.0001), and MI (HR 2.16, 95% CI 1.61-2.91, P < 0.0001). The events appeared earlier after primary PCI with more than 50% within the first month; after the first year, further occurrences were similar in both groups. Finally, the use of everolimus-eluting stents suggested the best safety profile. The present study shows that acute ischemic events are frequent after primary PCI and occur earlier compared with elective PCI. Particular attention should be directed towards optimal stent selection and implantation technique.

Hybrid strategy for unstable patients with severe carotid and cardiac disease requiring surgery

Concurrent severe carotid and cardiac disease is a challenging situation where staged surgery is probably the most common strategy. However, in patients with an unstable clinical presentation, the best approach is still a matter of debate. The aim of the study was to report in-hospital and midterm outcome in patients who received carotid artery stenting and synchronous cardiac surgery. From June 1998 to July 2012, 54 consecutive patients who were treated at a high-volume university medical center with this hybrid approach were included in the study. All of the patients received carotid angioplasty while being administered aspirin and regular unfractionated heparin. Then, all of the patients were immediately transferred to the operating room for coronary and/or cardiac valve surgery. All of the patients were administered aspirin and clopidogrel once bleeding was ruled out, after surgery. There were 5 in-hospital surgical related deaths, and no patient suffered a stroke or required carotid urgent re-intervention. At follow-up (55 ± 28 months; range 1-144 months), there were no new neurological deficits, while one additional death occurred. In this series, synchronous carotid stenting and cardiac surgery were feasible with an acceptable complication rate in a high-surgical-risk population, which could not undergo staged procedures.

New diagnosis without new treatments

The improvement of our investigative and diagnostic capability allows us to recognize early stage or mostly stable diseases in asymptomatic individuals and to treat those patients based on research conducted on more severe and acute conditions. Our main concern is avoiding not to treat a patient because of a missed diagnosis, so that we can avoid regrets and legal troubles. Usually, we do not take into account the opposite risk: overtreatment induced by overdiagnosis. For example, the increased number of diagnoses of pulmonary embolism did not reduce the incidence of death, but increased the number of bleeding from subsequent anticoagulation therapy. Similarly, the widespread detection of troponin increased the number of diagnoses of myocardial infarction solely on the basis of Lab values. In both cases we apply therapeutic strategies that have been proven effective in patients with more advanced and unstable clinical presentations with the risk of doing more harm than benefit. To be reassured by doing more, we risk to do worse.

Abstract T P94: Association Between Carotid Expansive Remodeling Determined by Long-axis High-resolution MRI and Unstable Clinical Presentation

Background and Purpose: Accumulating evidence from recent vascular biology studies has demonstrated that not only luminal narrowing but also plaque characteristics have large impact on the risk of ischemic events. The impact of expansive remodeling (ER) in atherosclerotic arterial disease on unstable clinical presentation has been extensively investigated in coronary circulation. The purpose of the present study was to investigate the association between carotid ER determined by MRI and cerebral ischemic events. Methods: Among prospectively collected data for patients with carotid artery (CA) stenosis scheduled for carotid endarterectomy (CEA) or carotid stenting, 122 CAs in 119 patients were identified. Excluding 22 CAs (contraindicated for MRI due to pacemaker implantation: 2, near-occlusion: 8, inadequate MRI due to poor image quality: 6, restenosis after CEA or CAS: 6), 100 CAs were finally analyzed in this study. The study included 50 symptomatic (73.6 ± 8.9 years; 6 female; %stenosis, 68.5± 21.3; 34 CEA) and 50 asymptomatic lesions (72.0 ± 5.9 years; 5 female; %stenosis, 79.4 ± 8.85; 15 CEA). ER ratio was calculated by dividing the maximal outside diameter at atherosclerotic plaque near the carotid bulb by the maximal outside diameter of the normal internal CA distal to the plaque with use of long-axis high-resolution MRI. Results: In 25 patients with unilateral carotid atherosclerosis, the ER ratio of atherosclerotic CA (1.68±0.40) was significantly greater (p&lt;.01) than that of the normal physiological expansion at a carotid bulb (1.36±0.15). The ER ratio of symptomatic CAs (1.93±0.44) was significantly greater (p&lt;0.0001) than that of asymptomatic CAs (1.63±0.30). When the cutoff value was set as 1.88, sensitivity and specificity were 0.6 and 0.78, respectively. The ER ratio of symptomatic CAs was consistently high regardless of % luminal stenosis. Conclusions: ER ratio measured with MRI might help to establish more accurate risk stratification for future cerebral ischemic events.

Zotarolimus-eluting stent-induced hypersensitivity pneumonitis

Zotarolimus-eluting stent-induced hypersensitivity pneumonitis

Longitudinal heterogeneity of coronary artery distensibility in plaques related to acute coronary syndrome

How coronary distensibility contributes to stable or unstable clinical manifestations remains obscure. We postulated that the heterogeneous plaque distensibility is associated with unstable clinical presentations in patients with acute coronary syndrome (ACS). Seventeen and 19 ACS-related and -unrelated lesions, respectively, were visualized using intravascular ultrasound imaging with simultaneous intracoronary pressure recording. Systolic and diastolic lumen cross-sectional areas were measured at the lesion site and at five evenly spaced sites between the proximal and distal reference sites. The coronary distensibility index and stiffness index β were calculated for each site and averaged for each coronary segment. Maximal distensibility index, standard deviation and the difference between maximal and minimal distensibility indices within each segment were significantly higher in the ACS-related than -unrelated plaques (5.6 ± 2.3 vs. 3.7 ± 1.8, p < 0.001, 2.1 ± 0.9 vs. 1.1 ± 0.6, p < 0.001 and 5.3 ± 2.3 vs. 2.8 ± 1.5, p < 0.001, respectively). Moreover, the difference in the distensibility index between the lesion site of ACS-related plaques and the immediate proximal site was significantly larger (2.88 ± 2.35 vs. 1.17 ± 1.44, p = 0.022) than that in ACS-unrelated plaques. Coronary artery distensibility is longitudinally more heterogeneous in ACS-related than-unrelated plaques, especially between the lesion and the immediate proximal site.

Sex difference in long-term clinical outcome after sirolimus-eluting stent implantation

Coronary stenting in women has been associated with worse results in terms of morbidity, mortality, and restenosis rate in the bare-metal stent era, possibly due to higher risk profile and smaller coronary vessels. Although drug-eluting stents have equalized clinical results, no data are available on long-term outcomes between sexes. To evaluate the role of sex in acute, mid-term, and long-term clinical outcome after sirolimus-eluting stent (SES) implantation. We retrospectively evaluated 1186 patients, 970 (81.8%) male and 216 (18.2%) female, treated with SES implantation between April 2002 and December 2005. Women were older (P=0.049), more likely to have hypertension (43.5 vs. 33.7%, P=0.006), single-vessel disease (63.9 vs. 42.5%, P=0.03), and unstable angina (16.6% vs. 9.2%, P=0.001) and more frequently received small (≤ 2.75 mm) vessel stenting (39.3 vs. 28.2%, P=0.001). The two groups were similar for lesion and procedural characteristics. Overall, the stent thrombosis rate was 0.4% (0.5% in women vs. 0.3% in men, P=not significant). At 6-month follow-up, no significant difference in major adverse cardiac event was observed. Long-term follow-up (median time 33.2 months), available in 180 (83.3%) women and 720 (75%) men, showed higher angina recurrence rate (17.7 vs. 11%, P=0.013), percutaneous coronary re-intervention (16.1 vs. 8.7%, P=0.001) and target vessel revascularization (3.9 vs. 0.9%, P=0.001) in women compared with men. Late stent thrombosis, need for coronary artery bypass grafting, and mortality were similar in both groups. No sex difference was observed in acute and 6-month outcome after SES implantation despite older age, more unstable clinical presentation, and more frequent small vessel stenting in women. However, long-term clinical follow-up (up to 5 years) in women showed higher symptom recurrence and target vessel revascularization rate but no difference in overall major adverse cardiac events.

Comparison of ruptured coronary plaques in patients with unstable and stable clinical presentation

It remains uncertain why some plaque ruptures trigger acute coronary syndrome (ACS), whereas others do not. We investigated the anatomic features and tissue factor (TF) expression at the sites of plaque rupture in 42 patients presenting with ACS (n=23) or stable angina (n=19). Intravascular ultrasound examination was performed before directional coronary atherectomy. Specimens were stained with antibodies against TF, CD68 positive phagocytic cells, and smooth muscle cells; and intravascular ultrasound and immunohistochemistry results were compared. Baseline demographic and clinical characteristics, as well as vessel and lumen sizes at both reference and lesion sites, were comparable in the two groups. However, the remodeling index and plaque burden at lesion sites were significantly greater in the ACS than in the stable angina group. The TF-immunopositive areas were significantly greater in the ACS than in the stable angina group (0.07%; IQR [0.02-0.16%] vs. 0.02%; IQR [0.01-0.05%], P=0.022), whereas the proportions of CD68-positive and smooth muscle cell areas were similar. There was a significant correlation between areas positive for TF and those positive for CD68 (r=0.83, P<0.001). In conclusion, ruptured plaques in patients with ACS show stronger TF expression, a greater plaque burden, and a higher remodeling index than do plaques in those with stable angina, suggesting that both lesion morphology and local thrombogenicity are related to clinical symptoms after plaque rupture.

Collagenase matrix metalloproteinase-8 expressed in atherosclerotic carotid plaques is associated with systemic cardiovascular outcome

Atherosclerotic plaque rupture and subsequent thrombus formation are the major cause of acute cardiovascular events. Local plaque markers may facilitate detection of the vulnerable plaque and help identify the patient at risk for cardiovascular events. Matrix metalloproteinases (MMPs) are prevalent in the arterial wall throughout the arterial system and are associated with local plaque destabilization. We hypothesized that local MMP plaque levels are predictive for atherosclerotic cardiovascular events in other vascular territories. Atherosclerotic plaques were obtained from 543 patients undergoing carotid endarterectomy (CEA). Plaques were analysed for the presence of macrophages, lipid-core, smooth muscle cells, collagen, calcification, and presence of plaque haemorrhage. MMP-2, MMP-8, and MMP-9 levels were assessed within the plaque. Following CEA, all patients underwent follow-up during 3 years. The primary outcome was defined as the composite of vascular death, non-fatal vascular event, and surgical or percutaneous vascular intervention. In contrast with MMP-2 plaque levels, MMP-8 and MMP-9 levels in the plaque were associated with an unstable carotid plaque composition and clinical presentation at baseline. Increased plaque MMP-8 level (>4.58) was associated with an increased risk for the occurrence of secondary manifestations of atherosclerotic disease during follow-up [hazard ratio = 1.76, 95% CI (1.25-2.48)] (P= 0.001), whereas plaque MMP-2 and MMP-9 levels were not predictive for systemic cardiovascular events. In contrast with MMP-2, increased carotid MMP-8 and MMP-9 plaque levels are associated with an unstable plaque phenotype. High collagenase MMP-8 levels in the carotid plaque are associated with the occurrence of systemic cardiovascular outcome during follow-up.

Volumetric evaluation of coronary plaque in patients presenting with acute myocardial infarction or stable angina pectoris—a multislice computerized tomography study

We hypothesized that unstable clinical presentation of coronary artery disease is associated with distinct characteristics of culprit lesions identifiable by multislice computed tomography (MSCT). Patients with non-ST-elevation myocardial infarction (NSTEMI) (n = 57) or stable angina (SA) pectoris (n = 19) were studied. Coronary culprit lesions in patients with NSTEMI and symptomatic lesions in patients with SA were evaluated with 64-slice MSCT and a volumetric plaque imaging tool. Plaque volumes of lipid, fibrous tissue, or calcification according to signal intensity were determined. Plaque burden, mean signal intensity of the lesions, relative volumetric distribution of plaque components, and remodeling index were measured. Volumetric plaque burden of study lesions were similar in the 2 patient groups (P = .38). Mean signal intensity of study lesions were lower in patients with NSTEMI compared with patients with SA (74 [66-97] Hounsfield units vs 99 [77-154] Hounsfield units, P = .02). The volume of plaque occupied by calcified material was lower in patients with NSTEMI compared with patients with SA (15 mm(3) [3-58 mm(3)] vs 42 mm(3) [18-82 mm(3)], P = .045). In patients with NSTEMI, the lipid-rich plaque subtype was more frequent than in patients with SA, and the calcified plaque subtype was less frequent in patients with NSTEMI than in patients with SA (P = .032). Positive remodeling was observed in 19% of patients with NSTEMI, whereas this was absent in patients with SA (P = .04). Volumetric measurements with MSCT revealed that coronary culprit lesions in acute coronary syndrome frequently display low mean plaque signal intensity values, lipid-rich plaque subtype, and positive remodeling.

In vivo association between positive coronary artery remodelling and coronary plaque characteristics assessed by intravascular optical coherence tomography

Positive coronary arterial remodelling has been shown to be associated with unstable coronary syndromes and ex vivo histological characteristics of plaque vulnerability such as a large lipid core and high macrophage content. The aim of this study is to evaluate the in vivo association between coronary artery remodelling and underlying plaque characteristics identified by optical coherence tomography (OCT). OCT is a unique imaging modality capable of characterizing these important morphological features of vulnerable plaque. OCT and intravascular ultrasound imaging was performed at corresponding sites in patients undergoing catheterization. OCT plaque characteristics for lipid content, fibrous cap thickness, and macrophage density were derived using previously validated criteria. Thin-cap fibroatheroma (TCFA) was defined as lipid-rich plaque (two or more quadrants) with fibrous cap thickness <65 microm. Remodelling index (RI) was calculated as the ratio of the lesion to the reference external elastic membrane area. A total of 54 lesions from 48 patients were imaged. Positive remodelling compared with absent or negative remodelling was more commonly associated with lipid-rich plaque (100 vs. 60 vs. 47.4%, P = 0.01), a thin fibrous cap (median 40.2 vs. 51.6 vs. 87 microm, P = 0.003) and the presence of TCFA (80 vs. 38.5 vs. 5.6%, P < 0.001). Fibrous cap macrophage density was also higher in plaques with positive remodelling showing a positive linear correlation with the RI (r = 0.60, P < 0.001). Coronary plaques with positive remodelling exhibit characteristic features of vulnerable plaque. This may explain the link between positive remodelling and unstable clinical presentations.

Do the extent and direction of arterial remodelling predict subsequent progression of coronary atherosclerosis? A serial intravascular ultrasound study

Objective: Despite the link between positive coronary remodelling and acute ischaemic events, no data exist about the impact of arterial remodelling on subsequent progression of coronary atherosclerosis. The objective of...

Impact of Stable Versus Unstable Coronary Artery Disease on 1-Year Outcome in Elective Patients Undergoing Multivessel Revascularization With Sirolimus-Eluting Stents: A Subanalysis of the ARTS II Trial

Impact of Stable Versus Unstable Coronary Artery Disease on One-Year Outcome in Elective Patients Undergoing Multivessel Revascularization With Sirolimus-Eluting Stents: A Subanalysis of the ARTS II Study Marco Valgimigli, Keith Dawkins, Carlos Macaya, Bernard de Bruyne, Emmanuel Teiger, Jean Fajadet, Richardt Gert, Stefano De Servi, Angelo Ramondo, Kristel Wittebols, Hans-Peter Stoll, Tessa A. M. Rademaker, Patrick W. Serruys We sought to address the impact of clinical presentation on outcome when 607 patients with multivessel disease in whom sirolimus-eluting stents were implanted, of whom 221 (36%) presented with unstable angina, were considered as part of a subanalysis of the ARTS II study. The actual cumulative rate of death, myocardial infarction, cerebrovascular accident, and repeat revascularization (i.e., major adverse cardiac and cerebrovascular events) was similar at both 30 days and 1 year in patients with unstable as compared with stable angina patients. After adjustment for baseline and procedural characteristics, the clinical presentation failed to be identified as an independent predictor of major adverse cardiac and cerebrovascular events (hazard ratio 0.94, 95% confidence interval 0.41 to 2.12, p = 0.88). We sought to evaluate the impact of unstable coronary artery disease (CAD) on short- and mid-term outcomes in patients with multivessel disease treated by multiple sirolimus-eluting stents (SES) as part of ARTS II (Arterial Revascularization Therapies Study Part II). The differential safety/efficacy profile of SES when implanted in patients with unstable angina (UA) in comparison with stable angina (SA) undergoing multivessel intervention is largely unknown. Between February 2003 and November 2003, 607 patients at 45 participating centers were treated; 221 of them (36%) presented with UA. At 30 days, the cumulative rate of death, myocardial infarction—defined as any creatine kinase (CK)/CK-myocardial band elevation beyond the upper limit of normal—cerebrovascular accident, and repeat revascularization (i.e., major adverse cardiac and cerebrovascular events [MACCEs]) was 19.9% in both groups. Angiographic subacute stent occlusion was documented in 1 (0.5%) and 4 (1%) patients in the UA and SA groups, respectively. At 1 year, the cumulative incidence of MACCEs was 27.1% in the UA and 24.9% in the SA group (p = 0.56). Two late occlusions occurred, both in the SA group. After adjustment for baseline and procedural characteristics, the presence of UA was not identified as an independent predictor of MACCE (hazard ratio 0.94; 95% confidence interval 0.41 to 2.12; p = 0.88). These findings remained consistent after increasing the CK/CK-myocardial band threshold to define periprocedural myocardial infarction up to at least 3 or 5 times the upper limit of normal. In ARTS II, an unstable clinical presentation did not exert a negative impact on short- and mid-term outcome after SES implantation for multivessel disease. (ARTS II Trial; http://clinicaltrials.gov/ct/show/NCT00235170?order=1 ; NCT00235170).

Characterizing the spectrum of in-stent restenosis: Implications for contemporary treatment

Reports addressing treatment of in-stent restenosis (ISR) are principally derived from clinical trials. To characterize the spectrum of ISR in an unselected population, and to explore clinical and angiographic factors determining management. During a prespecified six-month period before the introduction of drug-eluting stents, consecutive cases of ISR that were identified during clinically driven cardiac catheterization at five hospitals offering all approved treatment modalities for ISR were prospectively registered. ISR was identified in 363 patients; 301 (84%) had one ISR lesion and 62 (16%) had multiple lesions. Unstable clinical presentations accounted for 51%, including 15% with ST-elevation myocardial infarction. The median interval (25th, 75th percentiles) from stent insertion to angiographic diagnosis of ISR was eight months (Q1,Q3: 4,15), with a median stented length of 18 mm (Q1,Q3: 15,28). The majority of lesions (60%) displayed a diffuse ISR pattern (Mehran types 2 and 3). ISR type was independent of time to re-presentation, diabetes, arterial territory and total stent length. Treatment included percutaneous coronary intervention (PCI) alone (n=139 [38%]), PCI with brachytherapy (n=105 [29%]), medical therapy (n=60 [17%]) and coronary artery bypass graft surgery (n=59 [16%]). Medical therapy was associated with small vessel size and recurrent ISR, and coronary artery bypass graft surgery was associated with multiple lesions, as well as diffuse, occlusive and recurrent ISR. For patients treated percutaneously, PCI treatment alone was more common for focal restenosis and after ST-elevation myocardial infarction, and brachytherapy was the more common treatment for diffuse and recurrent ISR, and stable angina. These data provide a benchmark description of the spectrum of ISR with which the impact of drug-eluting stents may be compared and better understood.

Focal and multi-focal plaque macrophage distributions in patients with acute and stable presentations of coronary artery disease

This study was designed to utilize optical coherence tomography (OCT) images of coronary atherosclerotic plaque macrophages to investigate the relationship between macrophage distributions and clinical syndrome. The relative significance of focal macrophage infiltration and generalized coronary inflammation for predicting acute coronary events is a currently a source of considerable controversy in cardiology. Lack of a high-resolution cross-sectional imaging modality has limited macrophage evaluation in vivo. Intracoronary OCT imaging was performed at culprit and non-culprit plaques in patients presenting with stable angina pectoris, unstable angina pectoris,and ST-segment elevation myocardial infarction. Macrophage densities were quantified from these images and analyzed with respect to the clinical presentations of the patients under investigation. A significantly greater macrophage density was found in unstable patients, both for fibrous and lipid-rich plaques (p = 0.025 and p = 0.002, respectively). Within each patient, the macrophage densities at culprit and non-culprit lesions correlated significantly (r = 0.66, y = 0.88x + 0.43, p = 0.01). Sites of plaque rupture demonstrated a greater macrophage density than non-ruptured sites (6.95 +/- 1.60%, 5.29 +/- 1.17%; p = 0.002). Surface macrophage infiltration was a stronger predictor of unstable clinical presentation than subsurface infiltration for culprit lesions (p = 0.035) but not for remote lesions (p = 0.80). Our results demonstrate that increases in both multi-focal and focal macrophage densities are highly correlated with symptom severity. By providing a means of detecting increases in plaque macrophage content before an acute event, this technique may aid in determining prognosis and guiding preventive therapy.

Atherosclerosis Imaging

Most acute coronary syndromes result from the rupture or erosion of high-risk plaques. Clinical imaging studies have shown that atherosclerotic plaque formation and rupture are widespread processes that are often asymptomatic. The rationale for atherosclerosis imaging is the in-vivo identification of high-risk lesions, which may subsequently lead to prevention of future cardiovascular events. Although intravascular ultrasound (IVUS) imaging studies demonstrated that echolucent appearance of the plaque and expansive (positive) remodelling are associated with unstable clinical presentation, these characteristics were not adequate for accurate plaque characterisation. Recent technical developments in ultrasound equipment and analytical methods, utilising several characteristics of the digitised ultrasound signal with radiofrequency analysis and elastography, promise accurate tissue characterisation. Other imaging modalities, including optical coherence tomography, also contribute to a more precise characterisation of the composition of atherosclerotic plaques. A non-imaging approach is the focal assessment of temperature differences using sensitive intravascular thermography catheters, presumably reflecting focal inflammatory changes of vulnerable lesions. Although the histological characteristics of the atheroma are critically important in the sequence of events leading to acute coronary syndromes, the clinical relevance of identifying these characteristics is not yet clear. There is increasing evidence that identifying and treating individual culprit lesions may not be enough to prevent the ischaemic cardiac events in most patients, because the acute coronary syndrome is not a disease of a single site or a few discrete segments, but rather a systemic disease that involves the entire coronary tree. In addition to detection and quantitation of early coronary atherosclerosis and disease activity, accurate and reproducible methods could help to identify high-risk patients and allow serial monitoring during various therapeutic interventions. Serial IVUS imaging makes it possible to visualise the vessel wall that harbours the atheroma at different time points. Typically, serial IVUS allows the assessment of the percentage change in atheroma volume, with considerable statistical power to detect small changes. Using this methodology, aggressive lipid lowering by a high-dose statin agent has been shown to stop the progression of atherosclerosis, and a new mutant high-density lipoprotein complex was found to be effective in regressing atheroma burden. Although intravascular ultrasound is very accurate for quantification of atheroma burden, widespread application and accurate and reproducible non-invasive imaging modalities are needed for large-scale risk assessment algorithms. Cardiovascular computed tomography is at the forefront of the non-invasive imaging modalities. Future prospective imaging studies will be necessary to identify focal or systemic characteristics of high-risk lesions and to demonstrate the relationship between plaque burden, biochemical markers and clinical events.

Relation of matrix-metalloproteinase 3 found in coronary lesion samples retrieved by directional coronary atherectomy to intravascular ultrasound observations on coronary remodeling

We investigated the relation between the presence of matrix-metalloproteinases (MMPs) and direction of remodeling in the coronary lesions of 35 patients. Positive arterial remodeling describes a compensatory expansion of the external elastic membrane (EEM) area of atherosclerotic lesions. An association between positive remodeling and unstable clinical presentation has been previously described. However, the pathophysiology of the remodeling process is not completely understood. Preinterventional intravascular ultrasound images and directional atherectomy (DCA) samples were analyzed. The remodeling ratio was calculated as the EEM area at the lesion site divided by the EEM area at the proximal reference. Positive, intermediate, and negative remodeling were defined as ratios of >1.05, 0.95 to 1.05, and <0.95, respectively. The histologic samples were immunostained for MMP-1, -2, -3, and -9. Positive, intermediate, and negative remodeling was present in 15, 7, and 13 lesions, respectively. Mild and intense cell-associated staining for MMP-1 was found in 21 (68%) and 10 (32%) patients, respectively. Staining for MMP-3 was mild in 20 patients (67%) and intense in 10 patients (33%). Immunostaining for MMP-2 and -9 was mild in all samples. Intense staining for MMP-3 was significantly more common in lesions with positive than negative and/or intermediate remodeling (58% vs 17%; p = 0.04; p = 0.053 after adjustment for gender). Thus, in this in vivo intravascular ultrasound and histologic study, increased cell-associated MMP-3 staining was associated with positive arterial remodeling.

Autoantibody against, malondialdehyde-modified low density lipoprotein in patients with non-diabetic unstable angina: a potential role in immunologic reaction of plaque instability.

The role of autoantibody against oxidized low-density lipoprotein (LDL) in the pathogenesis of atherosclerosis is still unknown. The purpose of this study was to determine whether autoantibodies against malondialdehyde (MDA)-modified LDL are associated with coronary artery disease (CAD) and clinical presentations of CAD in non-diabetic patients without acute myocardial infarction (AMI). We determined the serum levels of autoantibody against MDA-modified LDL by ELISA in 71 patients with angiographically significant CAD (> or = 50% diameter stenosis in at least 1 vessel) and 80 controls without angiographically significant CAD. Among the total 151 subjects, 30 subjects did not have any clinical ischemic event, 90 subjects had stable angina symptoms, and 31 subjects had unstable angina symptoms. The autoantibody titer, expressed mean optical density units, was significantly higher in patients with CAD than in controls (0.177 +/- 0.014 versus 0.127 +/- 0.011, respectively; p=0.006) and higher in unstable angina group than in stable angina group (0.240 +/- 0.025 versus 0.145 +/- 0.007, respectively; p < 0.001). By logistic regression analysis, the high autoantibody titer was associated significantly with CAD (P=0.008), independent of age, gender, body mass index, triglyceride concentration, and the ratio of total cholesterol-high density lipoprotein (HDL) cholesterol. In multiple regression analysis, presence of CAD, smoking history and low HDL-cholesterol level were independent factors associated with a increased anti-oxLDL Ab titer. The autoantibody titer was significantly lower in nonsmoker than smoker (p=0.019) and higher in low HDL- cholesterol (< or = 35 mg/dl) group than in high HDL-cholesterol group (p=0.012). Elevated autoantibody titer was associated with CAD and the unstable clinical presentation of CAD. Our results suggest that immune response to oxidized LDL may play a role in the pathogenesis of atherosclerosis and plaque instability.