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Accumulating evidence from clinical trials suggests that a lower (restrictive) hemoglobin threshold (8% g/dL) for red blood cell (RBC) transfusion, compared with a higher (liberal) threshold (≥10 g/dL) is safe. However, in anemic patients with acute myocardial infarction (MI), maintaining a higher hemoglobin level may increase oxygen delivery to vulnerable myocardium resulting in improved clinical outcomes. Conversely, RBC transfusion may result in increased blood viscosity, vascular inflammation, and reduction in available nitric oxide resulting in worse clinical outcomes. We hypothesize that a liberal transfusion strategy would improve clinical outcomes as compared to a more restrictive strategy.We will enroll 3500 patients with acute MI (type 1, 2, 4b or 4c) as defined by the Third Universal Definition of MI and a hemoglobin10 g/dL at 144 centers in the United States, Canada, France, Brazil, New Zealand, and Australia. We randomly assign trial participants to a liberal or restrictive transfusion strategy. Participants assigned to the liberal strategy receive transfusion of RBCs sufficient to raise their hemoglobin to at least 10 g/dL. Participants assigned to the restrictive strategy are permitted to receive transfusion of RBCs if the hemoglobin falls below 8 g/dL or for persistent angina despite medical therapy. We will contact each participant at 30 days to assess clinical outcomes and at 180 days to ascertain vital status. The primary endpoint is a composite of all-cause death or recurrent MI through 30 days following randomization. Secondary endpoints include all-cause mortality at 30 days, recurrent adjudicated MI, and the composite outcome of all-cause mortality, nonfatal recurrent MI, ischemia driven unscheduled coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting), or readmission to the hospital for ischemic cardiac diagnosis within 30 days. The trial will assess multiple tertiary endpoints.The MINT trial will inform RBC transfusion practice in patients with acute MI.

Outcomes of patients presenting with non-ST-elevation acute coronary syndrome (NSTE-ACS) with multivessel coronary disease (MVD) and/or unprotected left main coronary artery disease (CAD) revascularized with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is not well defined. MEDLINE/PubMed and EMBASE/Ovid were queried for studies that investigated PCI vs CABG in this disease subset. The primary outcome was major cardiac adverse events (MACE) at 30 days and long-term follow-up (3-5 years). The final analysis included 9 studies with a total of 9299 patients. No significant difference was observed between PCI and CABG in 30 days MACE (risk ratio [RR] 0.96; 95% confidence interval [CI] 0.38-2.39, all-cause mortality, myocardial infarction, and stroke. A meta-regression analysis revealed patients with a history of PCI had higher risk of MACE with PCI as compared with CABG. At long-term follow-up, PCI compared with CABG was associated with higher risk of MACE (RR 1.52; 95% CI 1.28-1.81), myocardial infarction, and repeat revascularization, while no difference was observed in the risk of stroke and all-cause mortality. In patients with NSTE-ACS and MVD or unprotected left main CAD, no differences were observed in the clinical outcomes between PCI and CABG at 30 days follow-up. With long-term follow-up, PCI was associated with a higher risk of MACE.

Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in drastic changes to the practice of medicine, requiring healthcare systems to find solutions to reduce the risk of infection. Using a case series, we propose a protocol for same-day discharge (SDD) for selected patients undergoing transcatheter aortic valve replacement (TAVR) using real-time remote cardiac monitoring. Six patients with severe symptomatic aortic stenosis underwent TAVR and were discharged on the same day. Case summary Six patients with symptomatic severe native or bioprosthetic aortic valve stenosis underwent a successful transfemoral TAVR using standard procedures, including the use of rapid atrial pacing to assess the need for permanent pacemaker implantation. Following TAVR, patients were monitored on telemetry in the recovery area for 3 h, ambulated to assess vascular access stability, and discharged with real-time remote cardiac monitoring if no new conduction abnormality was observed. The patients were seen by tele-visits within 2 days and 2 weeks after discharge. Discussion Amidst the COVID-19 pandemic, SDD following successful transfemoral TAVR may be feasible for selected patients and reduce potential COVID-19 exposure.

Inferior vena cava filters (IVCF) are associated with complications which may be due to delayed retrieval. Initiation of an automated reminder system may improve retrieval rates and reduce complications. A computerized reminder system, which provides interactive email reminders after implantation while collecting IVCF use data, was implemented. IVCF retrieval was compared before ("reminder not provided" group) and after ("reminder provided" group) implementation. Data regarding implantation, retrieval, and complications were collected. The primary efficacy outcome was retrieval rate, and the primary safety outcome was indwelling complication rate. Secondary outcomes were time to retrieval and a composite adverse outcome defined as IVCF thrombosis, deep venous thrombosis (DVT), pulmonary embolism, and death. A total of 1,070 IVCF insertions were included, 715 in the "reminder not provided" group and 355 in the "reminder provided" group. Patient age (61 vs 64 years, p = 0.95) and gender (42% vs 40% female, p = 0.55) were similar in the "reminder not provided" and "reminder provided" groups, respectively. In the "reminder provided" group, the retrieval rate was higher (148/297 [49.8%] vs 223/715 [31.2%], p = 0.0001), the indwelling complication rate was lower (30/319 [9.4%] vs 115/715 [16.1%], p = 0.005), and the time to retrieval was shorter (112 days vs 146 days, p = 0.02). The composite adverse outcome occurred less frequently in the "reminder provided" group: (85/355 [23.9%] vs 297/715 [41.5%], p = 0.0001). The system was associated with increased odds of IVCF retrieval (odds ratio 2.56; 95% confidence interval: 1.82 to 3.59; p0.0001) and reduced odds of the composite adverse outcome (odds ratio 0.72; 95% confidence interval: 0.60 to 0.80; p0.0001). In conclusion, implementing a computerized email reminder system was associated with higher IVCF retrieval rates, fewer indwelling complications, and shorter dwell times.

IVCFs are usually placed under fluoroscopic guidance in dedicated angiography suites. Bedside placement of inferior vena cava filters (IVCF) is possible in patients not suitable for transportation, but data regarding their use are limited. The objective of this study is to compare utilization, procedural outcomes, complications, and long-term patient outcomes associated with bedside placement of IVCFs using intravascular ultrasound (IVUS) and fluoroscopic placement of IVCF.All patients receiving IVCF between January 2009 and December 2011 at a tertiary care institution were retrospectively identified. Data regarding patient characteristics, IVCF indications, complications, and outcomes were collected, and comparisons were made between patients receiving fluoroscopic-guided and IVUS-guided bedside IVCF.There were 117 bedside and 571 fluoroscopic-guided IVCF placed during this period. Patients receiving bedside IVCF were younger (50.8 vs. 60.7 years, P 0.001), less often had malignancy (22.2% vs. 42.6%, P 0.001), and received prophylactic filters more commonly (59.9% vs. 29.9%, P 0.001). Placement-related complications occurred in 4.3% and 0.6%, respectively (bedside IVCF: 4 malpositions, 1 severe tilt; fluoroscopic-guided IVCF: 1 malposition, 1 severe tilt, P = 0.01). Indwelling IVCF-related complications occurred equally during median follow-up of 463 and 488 days, respectively (deep vein thrombosis: 13.7% vs. 13.3%, P = 0.92; pulmonary embolism: 5.1% vs. 4.0%, P = 0.61; filter thrombosis: 3.4% vs. 3.9%, P = 0.82). Time to indwelling complication was similar between groups (74 vs. 127 days, P = 0.29).Bedside placement of IVUS-guided IVCF is safe, but with higher procedural complications when compared with fluoroscopic placement. Long-term indwelling complications are similar between IVCF placed via bedside IVUS guidance and fluoroscopic approach.

OBJECTIVES Complete coronary revascularization has been associated with improved mortality among patients undergoing surgical bypass grafting. A similar evaluation among patients undergoing percutaneous coronary intervention (PCI) for multivessel disease has produced largely concordant results, although complete percutaneous revascularization is often not achieved in this population. The present study sought to evaluate the clinical and anatomic limitations to complete revascularization among contemporary patients undergoing percutaneous revascularization for multivessel coronary artery disease. METHODS All patients undergoing nonemergent PCI for unprotected left main or multivessel coronary artery disease were identified at two academic medical centers from 2009 to 2012. Complete revascularization was determined through a review of the electronic medical records and corresponding coronary angiograms. The underlying reasons that precluded complete revascularization were then derived from a review of the clinical and angiographic findings. RESULTS Among 978 patients with multivessel coronary artery disease, 267 (27%) underwent complete percutaneous coronary revascularization. Factors that prevented complete revascularization included chronic total occlusions (54%), treatment limited to the culprit lesion (24%), or persistent disease in small nondominant vessels (24%). After multivariable adjustment, the presence of a chronic total occlusion was associated with significantly reduced odds of receiving complete revascularization (adjusted odds ratio: 0.18, 95% confidence interval: 0.12-0.27). CONCLUSION Complete percutaneous revascularization is uncommon and is hindered by the presence of chronic total occlusions or isolated treatment of an angiographic culprit lesion. Evolving interventional techniques enabling treatment of chronic total occlusions may increase the prevalence of complete percutaneous revascularization in the future.

Amlodipine toxicity is commonly reported medication involved in overdose. Its management involves early action with aggressive measures. We describe such a case managed successfully. 64-year-old female was admitted to hospital with severe hypotension and junctional rhythm 36 hours following

Objectives The primary objective of this study is the compare the association between bleeding and the use unfractionated heparin (UFH) versus bivalirudin during percutaneous coronary intervention (PCI). Background In patients undergoing PCI, the risk of bleeding with use of bivalirudin compared with UFH in the absence of glycoprotein IIb/IIIa inhibitors is not well defined. Methods: Patients undergoing PCI with either UFH or bivalirudin monotherapy at a single institution between 2007 and 2014 were included (n = 6,143). Propensity score matching was used to adjust for baseline characteristics yielding 2,984 well matched patients (1,492 in each group). The primary endpoint was major non-coronary artery bypass graft (non-CABG) related bleeding as defined by a Bleeding Academic Consortium type 3 or 5. Secondary outcomes included combined major and minor bleeding, in-hospital death, periprocedural myocardial infarction, and recurrent ischemia requiring urgent revascularization (repeat PCI). Results In the propensity matched cohort, there was no difference in major bleeding between UFH and bivalirudin monotherapy (1.8% versus 2.4%, P = 0.305). Combined major and minor bleeding was also similar between the two groups (4.3% versus 4.3%, P = 1.0). Likewise, no differences were observed between the bivalirudin and UFH groups in terms of in-hospital death (0.4% versus 0.5%, P = 0.592), periprocedural myocardial infarction (1.5% versus 2.0%, P = 0.332) and repeat PCI (0.7% versus 0.8%, P = 0.669). Conclusion Among patients undergoing PCI, there was no significant difference in rate of bleeding between bivalirudin and heparin monotherapy in a real-world setting. © 2015 Wiley Periodicals, Inc.

Mortality associated with high-risk pulmonary embolism (PE) remains high. Extra-corporeal membrane oxygenation (ECMO) allows for acute hemodynamic stabilization and potentially for administration of other disease process altering therapies. We sought to compare two eras: pre-ECMO and post-ECMO in relation to high-risk PE treatment and mortality. A single-center retrospective chart review was conducted of high-risk PE patients. High-risk PE was defined as acute PE and cardiac arrest or shock. A total of 60 patients were identified, 31 in the pre-ECMO era and 29 in the post-ECMO era. Mean age was 56.1±21.1 years and 51.7% were women. More patients in the post-ECMO era were identified with computed tomography (82.8% vs 51.6%, p=0.011) and more patients in the post-ECMO era had right ventricular dysfunction on echocardiography (96.4% vs 78.3%, p=0.045). No other differences were noted in baseline characteristics or clinical, laboratory and imaging data between the two groups. In total, ECMO was used in 13 (44.8%) patients in the post-ECMO era. There was greater utilization of catheter-directed therapies in the post-ECMO era compared to the pre-ECMO era ( n = 7 (24.1%) vs n = 1 (3.2%), p=0.024). Thirty-day survival increased from 17.2% in patients who presented in the pre-ECMO era to 41.4% in the post-ECMO era ( p=0.043). While more work is necessary to better identify those PE patients who stand to benefit from mechanical circulatory support, our findings have important implications for the management of such patients.

Objectives To compare intracoronary near-infrared spectroscopy (NIRS) and optical coherence tomography (OCT) for the detection of lipid, to identify NIRS signals to differentiate superficial lipid, and to characterize the plaque with yellow block (YB) chemograms on NIRS. Background Intracoronary NIRS has been developed to detect lipid core plaque (LCP). Methods We investigated a total of 17 patients who underwent both OCT and NIRS. NIRS analysis included plaque lipid core burden index (LCBI), LCP length, and the presence of YB on the block chemogram. OCT analysis included maximum lipid arc (LA), the length of lipid (LL), lipid index, and the thinnest fibrous cap thickness (FCT). Results Twenty-five plaques with >40% plaque burden were analyzed. LCP, showing LCBI > 0, was observed in 20 plaques (80%) and YB was detected in seven plaques (28%). Plaque LCBI showed modest correlations with maximum LA and lipid index by OCT (r2 = 0.319, P = 0.003 and r2 = 0. 404, P = 0.001, respectively). Lipid length showed a significant correlation between NIRS and OCT measurements (r2 = 0.581, P

Lymphatic vessels develop from specialized endothelial cells in preexisting blood vessels, but the molecular signals that regulate this separation are unknown. Here we identify a failure to separate emerging lymphatic vessels from blood vessels in mice lacking the hematopoietic signaling protein SLP-76 or Syk. Blood-lymphatic connections lead to embryonic hemorrhage and arteriovenous shunting. Expression of slp-76 could not be detected in endothelial cells, and blood-filled lymphatics also arose in wild-type mice reconstituted with SLP-76–deficient bone marrow. These studies reveal a hematopoietic signaling pathway required for separation of the two major vascular networks in mammals.

Objectives Patients with metastatic carcinoma and venous thromboembolism commonly have contraindications to anticoagulation that prompt the use of retrievable inferior vena cava filters. The aim of this study was to compare the pattern of inferior vena cava filter use, anticoagulation management, and development of inferior vena cava filter-related complications in patients with localized versus metastatic carcinoma. Methods We conducted a retrospective cohort study of inferior vena cava filter use at a tertiary referral hospital between January 1, 2009, and December 31, 2011. Including only patients with cancer and carcinomas, both metastatic and localized, we recorded the indications for inferior vena cava filter, postfilter practices including anticoagulation use, filter retrieval rates, and filter-related complications. Results Overall, 154 patients with carcinoma underwent inferior vena cava filter placement. Basic demographics and indication for filter placement were similar between the metastatic and localized groups. Metastatic patients had more filter-related complications (25% vs 11%, P = .03) and underwent filter retrieval less often (31% vs 58%, P = .01). Time to reinitiating anticoagulation was longer in metastatic patients (5.5 vs 2 days, P = .05). In multivariate analysis, metastatic disease was associated with reduced inferior vena cava filter retrieval (odds ratio, 0.3; P = .003). Anticoagulation use was associated with a lower rate of filter-related complications (odds ratio, 0.3; P = .005). Conclusions Patients with metastatic carcinoma with an indwelling inferior vena cava filter had a higher rate of filter-related complications, a lower filter retrieval rate, and a greater median time to initiating anticoagulation. When possible, early reinitiation of anticoagulation may reduce inferior vena cava filter-related complications.

Optical coherence tomography is a relatively novel imaging modality that utilizes light to generate high resolution images of intravascular structures. As result, OCT has rapidly become a preferred modality for imaging intracoronary structures such as coronary plaques and coronary stents. OCT is increasingly being utilized to further our understanding of intracoronary pathology and the effects of therapies both pharmacologic and procedural on the coronary vasculature. This review is intended to give an overview of the current investigational uses of OCT and its potential roles as the technology matures.

To the Editor: Previous studies have shown that plaque rupture and plaque erosion are the 2 most common underlying mechanisms for sudden cardiac death and acute coronary syndrome [(1,2)][1]. In a rupture, the exposure of the necrotic core to the circulation is the primary thrombogenic substrate

Recurrent myocardial infarctions and premature coronary atherosclerosis in a 23-year-old man with antiphospholipid syndrome

SummaryDevelopmental studies support a common origin for blood and endothelial cells, while studies of adult angiogenic responses suggest that the hematopoietic system can be a source of endothelial cells later in life. Whether hematopoietic tissue is a source of endothelial cells during normal vascular development is unknown. Mouse embryos lacking the signaling proteins Syk and Slp-76 develop abnormal blood-lymphatic endothelial connections. Here we demonstrate that expression of GFPSlp-76 in a subset of hematopoietic cells rescues this phenotype, and that deficient cells confer focal vascular phenotypes in chimeric embryos consistent with a cell-autonomous mechanism. Endogenous Syk and Slp-76, as well as transgenic GFPSlp-76, are expressed in circulating cells previously proposed to be endothelial precursors, supporting a causal role for these cells. These studies provide genetic evidence for hematopoietic contribution to vascular development and suggest that hematopoietic tissue can provide a source of vascular endothelial progenitor cells throughout life.

SLP76 and SLP65 are adaptor proteins that lack intrinsic enzymatic activity but contain multiple protein-binding domains. These proteins are essential for signalling downstream of integrins and receptors that contain immunoreceptor tyrosine-based activation motifs. The absence of these adaptor proteins profoundly affects various lineages in the haematopoietic compartment and severely compromises vascular development, highlighting their importance as regulators of signalling cascades. In this Review, we discuss the role of SLP76 and SLP65 in several signalling pathways in haematopoietic cells, with an emphasis on recent studies that provide insight into their mechanisms of action.

Insoluble pools of the amyloid-beta peptide (Abeta) in brains of Alzheimer's disease patients exhibit considerable N- and C-terminal heterogeneity. Mounting evidence suggests that both C-terminal extensions and N-terminal truncations help precipitate amyloid plaque formation. Although mechanisms underlying the increased generation of C-terminally extended peptides have been extensively studied, relatively little is known about the cellular mechanisms underlying production of N-terminally truncated Abeta. Thus, we used human NT2N neurons to investigate the production of Abeta11-40/42 from amyloid-beta precursor protein (APP) by beta-site APP-cleaving enzyme (BACE). When comparing undifferentiated human embryonal carcinoma NT2- cells and differentiated NT2N neurons, the secretion of sAPP and Abeta correlated with BACE expression. To study the effects of BACE expression on endogenous APP metabolism in human cells, we overexpressed BACE in undifferentiated NT2- cells and NT2N neurons. Whereas NT2N neurons produced both full-length and truncated Abeta as a result of normal processing of endogenous APP, BACE overexpression increased the secretion of Abeta1-40/42 and Abeta11-40/42 in both NT2- cells and NT2N neurons. Furthermore, BACE overexpression resulted in increased intracellular Abeta1-40/42 and Abeta11-40/42. Therefore, we conclude that Abeta11-40/42 is generated prior to deposition in senile plaques and that N-terminally truncated Abeta peptides may contribute to the downstream effects of amyloid accumulation in Alzheimer's disease.

Adapter proteins, molecules with modular domains that mediate intermolecular interactions, play critical roles in the regulation of signaling events in all cell types. A major focus of our laboratory has been to examine the role of adapter molecules in hematopoietic cell development and activation. This review will describe the approaches we are taking to identify such proteins and to determine the mechanisms by which they exert their functions. This work represents the enormous efforts of the students and postdocs who have committed themselves to these projects, as well as the important collaborations we have developed with other investigators at the University of Pennsylvania and elsewhere.

OBJECTIVES The aim of this study was to investigate the spatial location of vulnerable plaques at coronary artery bifurcations using frequency domain-optical coherence tomography. BACKGROUND In-vivo data on geometric location of vulnerable plaques in relation to coronary bifurcation are limited. MATERIALS AND METHODS A total of 40 patients with left anterior descending artery bifurcation were studied. Plaque characteristics in five regions in relation to a side branch were compared: opposite flow divider (OFD); bifurcation site (BF); main branch side proximal (MBP); side branch side proximal (SBP); and flow divider (FD). Frequency domain-optical coherence tomography was used for plaque characterization. RESULTS Seventy-two lipid-rich plaques and 15 thin-cap fibroatheroma (TCFA) were detected in 220 regions of 44 bifurcations. Overall, the main branch side had more vulnerable characteristics compared with the side branch side. The FD was rarely affected by lipid accumulation. The OFD showed the highest prevalence of lipid-rich plaques [47.7% (OFD) vs. 45.5% (MBP), 43.2% (BF), 18.2% (SBP), and 9.1% (FD), P

The primary objective of this study is the compare the association between bleeding and the use unfractionated heparin (UFH) versus bivalirudin during percutaneous coronary intervention (PCI).In patients undergoing PCI, the risk of bleeding with use of bivalirudin compared with UFH in the absence of glycoprotein IIb/IIIa inhibitors is not well defined.Patients undergoing PCI with either UFH or bivalirudin monotherapy at a single institution between 2007 and 2014 were included (n = 6,143). Propensity score matching was used to adjust for baseline characteristics yielding 2,984 well matched patients (1,492 in each group). The primary endpoint was major non-coronary artery bypass graft (non-CABG) related bleeding as defined by a Bleeding Academic Consortium type 3 or 5. Secondary outcomes included combined major and minor bleeding, in-hospital death, periprocedural myocardial infarction, and recurrent ischemia requiring urgent revascularization (repeat PCI).In the propensity matched cohort, there was no difference in major bleeding between UFH and bivalirudin monotherapy (1.8% versus 2.4%, P = 0.305). Combined major and minor bleeding was also similar between the two groups (4.3% versus 4.3%, P = 1.0). Likewise, no differences were observed between the bivalirudin and UFH groups in terms of in-hospital death (0.4% versus 0.5%, P = 0.592), periprocedural myocardial infarction (1.5% versus 2.0%, P = 0.332) and repeat PCI (0.7% versus 0.8%, P = 0.669).Among patients undergoing PCI, there was no significant difference in rate of bleeding between bivalirudin and heparin monotherapy in a real-world setting.

Background Popliteal vein aneurysm (PVA) may be an incidental finding on imaging, but often presents in the context of acute venous thromboembolism (VTE). The role of anticoagulation with or without surgical excision versus expectant management is ill defined. Methods In this single-center, retrospective, cohort study, patient records from January 2002 to December 2013 were queried for terminology consistent with PVA. Demographic data and clinical outcomes were extracted via chart review. Results A total of 21 patients with PVA were identified (57% male). Mean follow-up was 38 ± 31 months. Mean PVA diameter was 2.5 ± 1.1 cm; 67% were saccular (with the remainder being fusiform), 19% contained thrombus, 67% were left sided, and bilateral PVA was present in 24% of cases. At the time of PVA diagnosis, 14% had pulmonary embolism. Treatment consisted of observation only (62%), anticoagulation (19%), surgery (5%), or both anticoagulation and surgery (14%). There were no recurrences of VTE once treated, although there was 1 acute deep venous thrombosis in a patient who was managed conservatively. Two patients had recurrent PVA after surgery, and there were 2 surgical complications (transient foot drop and hematoma). Conclusions PVA is associated with VTE. Based on our series, it is unclear if incidentally discovered PVA (without VTE) warrants treatment with anticoagulation and/or surgical repair. Further multicenter studies are needed to establish the indications for safety and durability of surgery.

Smoking is associated with high incidence of cardiovascular events including acute coronary syndrome. We sought to characterize coronary plaques in patients with ongoing smoking using optical coherence tomography (OCT) compared with former smokers and nonsmokers. We identified 465 coronary plaques from 182 subjects who underwent OCT imaging for all 3 coronary arteries. Subjects were divided into 3 groups: current smokers (n = 41), former smokers (n = 67), and nonsmokers (n = 74). OCT analysis included the presence of lipid-rich plaque, thin-cap fibroatheroma (TCFA), calcification, maximum lipid arc, lipid core length, lipid index, and fibrous cap thickness. Lipid index was defined by mean lipid arc multiplied by lipid core length. Compared with former smokers and nonsmokers, the incidence of lipid plaques and TCFA was significantly higher in current smokers (lipid plaques: 68.0% vs 45.9% and 52.6%, p = 0.002; TCFA: 18.4% vs 7.6% and 9.9%, p = 0.018). There was a trend for higher plaque disruption in current smokers. Former smokers were more likely to have calcified plaques than current and nonsmokers (52.9% vs 32.0% and 38.0%, p = 0.001). In a multivariate analysis, current smoking, low-density lipoprotein, and presentation with acute coronary syndrome were independently associated with the presence of TCFAs. In conclusion, current smokers are more likely to have lipid plaques and OCT-defined vulnerable plaques (TCFAs). Former smokers have increased number of calcified plaques. These results may explain the increased risk of acute cardiac events among smokers.

Venous thromboembolism contributes significantly to morbidity and mortality in cancer patients. Because cancer patients frequently have contraindications to anticoagulation, inferior vena cava filters are commonly placed. The use, safety, and retrieval of retrievable inferior vena cava filters in cancer patients have not been well studied.A retrospective review of retrievable inferior vena cava filter use at a tertiary referral hospital was conducted between January 1, 2009 and December 31, 2011. Indications for inferior vena cava filter placement, anticoagulation practices, complications, filter retrieval, and patient outcomes were analyzed for patients with and without active cancer and for cancer subtypes, including localized and metastatic cases.Of 666 patients receiving retrievable inferior vena cava filters during this time period, 247 (37.1%) had active cancer. Of these, 151 (22.7%) had carcinoma, 92 (13.8%) had sarcoma, and 115 (17.3%) had metastatic disease. Overall, follow-up was available for a median of 401.0 (interquartile range: 107.5-786.5) days. Indwelling filter-related complications occurred in 19.8% of patients without cancer and 17.7% with an active cancer (P = .50). Patients with cancer were less likely to have the filter retrieved (28.0% vs 42.0%, P.001). In multivariable analysis, cancer was not associated with filter-related complications but was associated with a lower rate of filter retrieval.In a modern cohort of patients undergoing retrievable inferior vena cava filter placement, active diagnosis of cancer is not associated with a significant increase in filter-related complications, but is associated with a reduced rate of filter retrieval.

Mice engineered to express a transgene encoding a human Cu/Zn superoxide dismutase (SOD1) with a Gly93 --> Ala (G93A) mutation found in patients who succumb to familial amyotrophic lateral sclerosis (FALS) develop a rapidly progressive and fatal motor neuron disease (MND) similar to amyotrophic lateral sclerosis (ALS). Hallmark ALS lesions such as fragmentation of the Golgi apparatus and neurofilament (NF)-rich inclusions in surviving spinal cord motor neurons as well as the selective degeneration of this population of neurons were also observed in these animals. Since the mechanism whereby mutations in SOD1 lead to MND remains enigmatic, we asked whether NF inclusions in motor neurons compromise axonal transport during the onset and progression of MND in a line of mice that contained approximately 30% fewer copies of the transgene than the original G93A (Gurney et al., 1994). The onset of MND was delayed in these mice compared to the original G93A mice, but they developed the same neuropathologic abnormalities seen in the original G93A mice, albeit at a later time point with fewer vacuoles and more NF inclusions. Quantitative Western blot analyses showed a progressive decrease in the level of NF proteins in the L5 ventral roots of G93A mice and a concomitant reduction in axon caliber with the onset of motor weakness. By approximately 200 d, both fast and slow axonal transports were impaired in the ventral roots of these mice coincidental with the appearance of NF inclusions and vacuoles in the axons and perikarya of vulnerable motor neurons. This is the first demonstration of impaired axonal transport in a mouse model of ALS, and we infer that similar impairments occur in authentic ALS. Based on the temporal correlation of these impairments with the onset of motor weakness and the appearance of NF inclusions and vacuoles in vulnerable motor neurons, the latter lesions may be the proximal cause of motor neuron dysfunction and degeneration in the G93A mice and in FALS patients with SOD1 mutations.

Retrievable inferior vena cava filters (IVCFs) were designed to provide temporary protection from pulmonary embolism in high-risk situations. However, little is known about their effectiveness, and many remain permanently implanted, leading to potential complications. The aim of this study was to determine patient characteristics, indications for IVCF placement, retrieval rates, complications, and post-IVCF anticoagulation (AC) practices in patients who have received IVCFs. A retrospective review of IVCF use by 3 specialty groups from January 1, 2009, to December 31, 2011, was conducted at a tertiary referral center. Indications for IVCF, procedural success and complications, post-IVCF AC practices, and patient outcomes were assessed. Seven hundred fifty-eight IVCFs were placed. Follow-up was available for 688 patients (90.7%) at a median of 342.0 days (interquartile range 81.5 to 758.0). Indications for IVCF placement included contraindication to AC in the presence of acute venous thromboembolism (n = 287 [41.7%]) and prophylaxis (n = 235 [34.2%]). Insertion-related complications occurred in 28 patients (4.1%). After IVCF placement, adequate AC was initiated in 454 patients (66.0%)3.0 days (interquartile range 0 to 13.0) after insertion, but the overall retrieval rate was only 252 of 688 (36.6%) within a median of 134.0 days (interquartile range 72.50 to 205.8). Significant IVCF-related complications occurred in 122 patients (17.7%) within 32 days (interquartile range 13.0 to 116.8). The most common complication (72 of 131 [55.0%]) was deep vein thrombosis. In conclusion, in a large, modern cohort of patients receiving retrievable IVCFs for a variety of indications by various specialties, IVCF insertion remains safe. However, many patients have IVCF-related complications, and often, even when IVCFs are retrieved, there is a delay between AC and retrieval. Quality improvement initiatives that facilitate the expeditious retrieval of IVCF are needed.

Background Recent studies described different clinical and underlying plaque characteristics between patients with and without plaque rupture presenting with acute coronary syndrome (ACS). In light of the systemic nature of atherosclerosis, we hypothesized that nonculprit plaques might also express different morphological features in these 2 groups of patients. Methods Thirty-eight patients with ACS who underwent 3-vessel optical coherence tomography imaging were identified from the Massachusetts General Hospital Optical Coherence Tomography Registry. Based on culprit plaque morphology, the study population was divided into 2 groups: patients with plaque rupture at the culprit lesion (group 1) and patients with nonruptured plaque at the culprit lesion (group 2). Prevalence and features of nonculprit plaques were compared between the 2 groups. Results A total of 118 nonculprit plaques were analyzed. Patients in group 1 (n = 17) had nonculprit plaques with higher prevalence of thin-cap fibroatheroma (52.9% vs 19.0%, P = .029) and disruption (35.3% vs 4.8%, P = .016) compared with patients in group 2 (n = 21). Nonculprit plaques in group 1 showed wider maximum lipid arc (198.9° ± 41.7° vs 170.2° ± 41.9°, P = .003), greater lipid length (7.8 ± 4.4 mm vs 5.1 ± 2.4 mm, P = .003), higher lipid index (1196.9 ± 700.5 vs 747.7 ± 377.3, P = .001), and thinner fibrous cap (107.0 ± 56.5 μm vs 137.3 ± 69.8 μm, P = .035) compared with those in group 2. Conclusions The present study showed distinctive features of nonculprit plaques between patients with ACS caused by plaque rupture and patients with ACS caused by nonruptured plaques. Patients with plaque rupture had increased pancoronary vulnerability in nonculprit plaques, suggesting that a more aggressive treatment paradigm aiming at the stabilization of vulnerable plaques may offer additional benefit to these patients.

ObjectivesThe aim of this study was to characterize the morphological features of plaque erosion and calcified nodule in patients with acute coronary syndrome (ACS) by optical coherence tomography (OCT).BackgroundPlaque erosion and calcified nodule have not been systematically investigated in vivo.MethodsA total of 126 patients with ACS who had undergone pre-intervention OCT imaging were included. The culprit lesions were classified as plaque rupture (PR), erosion (OCT-erosion), calcified nodule (OCT-CN), or with a new set of diagnostic criteria for OCT.ResultsThe incidences of PR, OCT-erosion, and OCT-CN were 43.7%, 31.0%, and 7.9%, respectively. Patients with OCT-erosion were the youngest, compared with those with PR and OCT-CN (53.8 ± 13.1 years vs. 60.6 ± 11.5 years, 65.1 ± 5.0 years, p = 0.005). Compared with patients with PR, presentation with non–ST-segment elevation ACS was more common in patients with OCT-erosion (61.5% vs. 29.1%, p = 0.008) and OCT-CN (100% vs. 29.1%, p

Emerging evidence suggests that neointimal degenerative changes with development of neoatherosclerosis (NA) may represent an important mechanism for late stent failure. The aim of the present study was to investigate the relation between degree of neointimal hyperplasia and incidence and characteristics of NA using optical coherence tomography. We identified a total of 252 stents with mean neointimal thickness (NIT)100 μm in 212 patients: 100 bare metal stents (BMSs) and 152 drug-eluting stents (DESs). Based on the values of mean NIT, we divided stents into tertiles and compared neointimal characteristics among the 3 groups. NA was defined as the presence of lipid-laden intima and/or calcification inside the stent. In both BMS and DES, there was a difference in the prevalence of lipid-laden intima among the tertiles (18.2% vs 36.4% vs 47.1%, p = 0.042 [BMS]; 19.6% vs 56.9% vs 88.0%, p0.001 [DES]). However, no difference in the prevalence of in-stent calcification was observed (21.2% vs 21.2% vs 2.9%, p = 0.053 [BMS]; 5.9% vs 9.8% vs 2.0%, p = 0.252 [DES]). In a multivariate model adjusting for stent type, follow-up duration, conventional coronary risk factors, statin, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blockade use, mean NIT was independently associated with the presence of NA (odds ratio 2.53, 95% confidence interval 1.96 to 3.27, p0.001). This study demonstrates the presence of a positive correlation between degree of neointimal hyperplasia after stent implantation and presence of lipid-laden intima. This association is independent from stent type and time from implantation and suggests a possible pathogenic link between the two processes.

Background— Chronic kidney disease (CKD) promotes the development of atherosclerosis and increases the risk of cardiovascular disease. The aim of the present study was to compare the coronary plaque characteristics of patients with and without CKD using optical coherence tomography. Methods and Results— We identified 463 nonculprit plaques from 287 patients from the Massachusetts General Hospital (MGH) optical coherence tomography registry. CKD was defined as estimated glomerular filtration rate 2 . A total of 402 plaques (250 patients) were in the non-CKD group and 61 plaques (37 patients) were in the CKD group. Compared with non-CKD plaques, plaques with CKD had a larger lipid index (mean lipid arc×lipid length, 1248.4±782.8 mm° [non-CKD] versus 1716.1±1116.2 mm° [CKD]; P =0.003). Fibrous cap thickness was not significantly different between the groups. Calcification (34.8% [non-CKD] versus 50.8% [CKD]; P =0.041), cholesterol crystals (11.2% [non-CKD] versus 23.0% [CKD]; P =0.048), and plaque disruption (5.5% [non-CKD] versus 13.1% [CKD]; P =0.049) were more frequently observed in the CKD group. In the multivariate linear regression model, a lower estimated glomerular filtration rate and diabetes mellitus were independent risk factors for a larger lipid index. Conclusions— Compared with non-CKD patients, the patients with CKD had a larger lipid index with a higher prevalence of calcium, cholesterol crystals, and plaque disruption. The multivariate linear regression model demonstrated that a lower estimated glomerular filtration rate was an independent risk factor for a larger lipid index. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01110538.

To compare intracoronary near-infrared spectroscopy (NIRS) and optical coherence tomography (OCT) for the detection of lipid, to identify NIRS signals to differentiate superficial lipid, and to characterize the plaque with yellow block (YB) chemograms on NIRS.Intracoronary NIRS has been developed to detect lipid core plaque (LCP).We investigated a total of 17 patients who underwent both OCT and NIRS. NIRS analysis included plaque lipid core burden index (LCBI), LCP length, and the presence of YB on the block chemogram. OCT analysis included maximum lipid arc (LA), the length of lipid (LL), lipid index, and the thinnest fibrous cap thickness (FCT).Twenty-five plaques with40% plaque burden were analyzed. LCP, showing LCBI0, was observed in 20 plaques (80%) and YB was detected in seven plaques (28%). Plaque LCBI showed modest correlations with maximum LA and lipid index by OCT (r(2) = 0.319, P = 0.003 and r(2) = 0. 404, P = 0.001, respectively). Lipid length showed a significant correlation between NIRS and OCT measurements (r(2) = 0.581, P0.001). There was no significant difference in NIRS parameters between superficial and deep lipid. Plaques with YB compared with those without YB showed a larger LA, longer LL, and thinner FCT (185 ± 29° vs. 105 ± 76°, P = 0.014; 8.5 ± 3.3 mm vs. 3.3 ± 2.7 mm, P = 0.001; 112 ± 42 vs. 166 ± 61 µm, P = 0.033).NIRS and OCT parameters showed modest linear correlations in the measurement of lipid. The accurate depth of lipid in the vessel wall could not be identified by quantitative NIRS parameters. YB chemograms represented more vulnerable features on OCT.

Background— The pathophysiological basis for the association between metabolic syndrome (MetS) and coronary artery disease is not well understood. We sought to characterize coronary plaques in patients with MetS by using optical coherence tomography. Methods and Results— We identified 451 coronary plaques from 171 subjects who underwent optical coherence tomographic imaging in 3 coronary arteries. Subjects were divided into 3 groups: diabetes mellitus (DM, n=77), MetS (n=35), and a control group (C group, n=59) without DM or MetS. Optical coherence tomographic analysis included the presence of lipid-rich plaque, maximum lipid arc, lipid-core length, lipid index (LI), fibrous cap thickness, and thin-cap fibroatheroma. We defined LI as mean lipid arc multiplied by lipid-core length. Lipid-core length and LI were significantly greater in DM and MetS than in C group (lipid-core length: 7.7±4.0 and 7.0±3.8 versus 5.5±2.4 mm; P P =0.012, and LI: 1164±716 and 1086±693 versus 796±417 mm; P P =0.008). Maximum lipid arc was significantly greater in DM than in C group, whereas no significant difference was observed between MetS and C group (196±45°, 187±42° versus 176±52°; P =0.002 and P =0.182). Fibrous cap thickness and thin-cap fibroatheroma showed no significant difference among the 3 groups. In multivariate analysis, DM and MetS were independently associated with LI, whereas only acute coronary syndrome was the independent predictor for thin-cap fibroatheroma. Conclusions— Compared with control subjects, coronary plaques in MetS contain larger lipid. However, the MetS criteria used in this study could not distinguish the vulnerable features such as thin-cap fibroatheroma, suggesting the necessity of complementary information to identify patients at high risk for cardiovascular events.

A 60-year-old man was transferred to the catheterization laboratory after a witnessed ventricular fibrillation arrest. The electrocardiogram was remarkable for ST-segment elevations in leads II, III, aVF, and V6, with reciprocal ST-segment depression in leads V1 to V4 and aVL ([Fig. 1][1]). The