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Vascular beds show different propensities for different vascular pathologies, yet mechanisms explaining these fundamental differences remain unknown. We sought to build a transcriptomic, cellular, and spatial atlas of human arterial cells across multiple different arterial segments to understand this phenomenon. We found significant cell type-specific segmental heterogeneity. Determinants of arterial identity are predominantly encoded in fibroblasts and smooth muscle cells, and their differentially expressed genes are particularly enriched for vascular disease-associated loci and genes. Adventitial fibroblast-specific heterogeneity in gene expression coincides with numerous vascular disease risk genes, suggesting a previously unrecognized role for this cell type in disease risk. Adult arterial cells from different segments cluster not by anatomical proximity but by embryonic origin, with differentially regulated genes heavily influenced by developmental master regulators. Non-coding transcriptomes across arterial cells contain extensive variation in lnc-RNAs expressed in cell type- and segment-specific patterns, rivaling heterogeneity in protein coding transcriptomes, and show enrichment for non-coding genetic signals for vascular diseases.

Background: Contemporary series of aortic arch replacement at the time of aortic root surgery are limited in number of patients and mostly address hemiarch replacement. We describe outcomes after aortic root and concomitant arch replacement, including total arch replacement., Methods: This single-institution retrospective review studied 1196 consecutive patients from May 2004 to September 2020 who underwent first-time aortic root replacement. Patients undergoing surgery for endocarditis were excluded (n = 68, 5.7%). Patients undergoing concomitant root and arch replacement were propensity matched with patients undergoing isolated root surgery based on indication, clinical and operative characteristics, demographics, medical history including connective tissue disorders, and urgency. Multivariable Cox proportional hazards and logistic regression modeling were used to assess the primary outcome of all-cause mortality and the secondary outcomes of prolonged ventilator use, postoperative blood transfusion, and debilitating stroke, adjusted for patient and operative characteristics., Results: Among the 1128 patients who underwent aortic root intervention during the study period, 471 (41.8%) underwent concomitant aortic arch replacement. Most underwent hemiarch replacement (n = 411, 87.4%); 59 patients (12.6%) underwent total arch replacement (with elephant trunk: n = 23, 4.9%; without elephant trunk: n = 36, 7.7%). The mean follow-up time was 4.6 years postprocedure. Operative mortality was 2.2%, and total mortality over the entire study period was 9.2%. Propensity matching generated 348 matches (295 concomitant hemiarch, 53 concomitant total arch). Concomitant hemiarch (hazard ratio, 1.00; 95% confidence interval, 0.54-1.86, P  = .99) and total arch replacement (hazard ratio, 1.60, 95% confidence interval, 0.72-3.57, P  = .24) were not significantly associated with increased mortality. Rates of stroke were not significantly different among each group: isolated root (n = 11/348, 3.7%), root + hemiarch (n = 17/295, 5.8%), and root + total arch (n = 3/53, 5.7%) replacement ( P  = .50), nor was the adjusted risk of stroke. Both concomitant arch interventions were associated with prolonged ventilator use and use of postoperative blood transfusions., Conclusions: Hemiarch and total arch replacement are safe to perform at the time of aortic root intervention, with no significant differences in survival or stroke rates, but increased ventilator and blood product use., (© 2023 The Author(s).)

Background: The aim of this study was to evaluate the role of the distance between the aortic valve in projected position to the coronary ostium to determine risk of coronary artery obstruction after transcatheter aortic valve replacement (TAVR)., Methods: An Expected Leaflet-to-ostium Distance (ELOD) was obtained on pre-TAVR planning computed tomography by subtracting leaflet thickness and the distances from the center to the annular rim at annulus level and from the center to the coronary ostium at mid-ostial level. Variables were compared between patients with and without coronary obstruction and the level of association between variables was assessed using log odds ratio (OR)., Results: A total of 177 patients with 353 coronary arteries was analyzed. Mean annulus diameters (22.8 ± 2.8 mm and 23.4 ± 1.0 mm, p > 0.05) and mean sinus of Valsalva (SOV) diameters (31.2 ± 3.6 mm and 31.9 ± 3.6 mm, p > 0.05) were similar between patients with lower and higher coronary heights, respectively. There were three coronary obstruction cases. ELOD ≤ 2 mm in combination with leaflet length longer than mid-ostial height allowed for discrimination of cases with and without coronary obstruction. There was a significant association between coronary obstruction event and ELOD ≤ 2 mm (log OR = 6.180, p < 0.001)., Conclusions: Our study showed that a combination of ELOD < 2 mm and a longer leaflet length than mid-ostial height may be associated with increased risk for coronary obstruction during TAVR., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Background: Thoracic endovascular aortic repair (TEVAR) has become first-line treatment for descending thoracic aortic rupture (DTAR), but its midterm and long-term outcomes remain undescribed. This study evaluated whether TEVAR would improve midterm outcomes of nontraumatic DTAR relative to open surgical repair (OSR)., Methods: Between December 1999 and October 2018, 118 patients with DTAR were treated with either OSR (n = 39) or TEVAR (n = 79) at a single center. Primary end points were 30-day and long-term all-cause mortalities. Secondary end points included stroke, permanent spinal cord ischemia (SCI), prolonged ventilation support or tracheostomy, permanent hemodialysis, and aortic reintervention., Results: Thirty-day mortality was significantly lower with TEVAR (OSR, 38.5%; TEVAR, 16.5%; P = .01). Stroke (15.6% vs 3.8%; P = .03), permanent SCI (15.6% vs 2.5%; P = .02), prolonged ventilation (30.8% vs 8.9%; P = .002), and tracheostomy (12.8% vs 2.5%; P = .04) were significantly lower after TEVAR than OSR. Need for hemodialysis trended higher after OSR (12.8% vs 5.1%; P = .2). Mean follow ups were 1048 ± 1591 days for OSR group and 828 ± 1258 days for TEVAR. All-cause mortality at last follow-up was significantly lower after TEVAR than OSR (35.4% vs 66.7%; P = .001). Aortic reintervention was required more frequently within 30 days after TEVAR (15.2% vs 2.6%; P = .06). By multivariate analysis, TAAA was an independent predictor for mortality., Conclusions: TEVAR improves both early and midterm outcomes of DTAR relative to OSR. TAAA was a predictor of mortality. Endovascular approach to DTAR may provide the greatest chance at survival., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Depression is a significant concern after cardiac surgery and has not been studied in patients undergoing transcatheter aortic valve replacement (TAVR). We sought to examine the prevalence of pre-procedure depression and anxiety symptoms and explore whether brief bedside cognitive behavioral therapy (CBT) could prevent post-TAVR psychological distress., Methods: We prospectively recruited consecutive TAVR patients and randomized them to receive brief CBT or treatment as usual (TAU) during their hospitalization. Multi-level regression techniques were used to evaluate changes by treatment arm in depression, anxiety, and quality of life from baseline to 1 month post-TAVR adjusted for sex, race, DM, CHF, MMSE, and STS score., Results: One hundred and forty six participants were randomized. The mean age was 82 years, and 43% were female. Self-reported depression and anxiety scores meeting cutoffs for clinical level distress were 24.6% and 23.2% respectively. Both TAU and CBT groups had comparable improvements in depressive symptoms at 1-month (31% reduction for TAU and 35% reduction for CBT, p = .83). Similarly, both TAU and CBT groups had comparable improvements in anxiety symptoms at 1-month (8% reduction for TAU and 11% reduction for CBT, p = .1). Quality of life scores also improved and were not significantly different between the two groups., Conclusions: Pre-procedure depression and anxiety may be common among patients undergoing TAVR. However, TAVR patients show spontaneous improvement in depression and anxiety scores at 1-month follow up, regardless of brief CBT. Further research is needed to determine whether more tailored CBT interventions may improve psychological and medical outcomes., Competing Interests: Declaration of Competing Interest Dr. Lee has received lecture fees of less than $10,000 from Edwards LifeSciences in 2017. Dr. Fearon has received institutional research support from Edwards LifeSciences. Other authors report no relationships that could be construed as a conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: To develop a segmentation pipeline for segmentation of aortic dissection CT angiograms into true and false lumina on multiplanar reformations (MPRs) perpendicular to the aortic centerline and derive quantitative morphologic features, specifically aortic diameter and true- or false-lumen cross-sectional area., Materials and Methods: An automated segmentation pipeline including two convolutional neural network (CNN) segmentation algorithms was developed. The algorithm derives the aortic centerline, generates MPRs orthogonal to the centerline, and segments the true and false lumina. A total of 153 CT angiograms obtained from 45 retrospectively identified patients (mean age, 50 years; range, 22-79 years) were used to train ( n = 103), validate ( n = 22), and test ( n = 28) the CNN pipeline. Accuracy was evaluated by using the Dice similarity coefficient (DSC). Segmentations were then used to derive the maximal diameter of test-set patients and cross-sectional area profiles of the true and false lumina., Results: The segmentation pipeline yielded a mean DSC of 0.873 ± 0.056 for the true lumina and 0.894 ± 0.040 for the false lumina of test-set cases. Automated maximal diameter measurements correlated well with manual measurements ( R 2 = 0.95). Profiles of cross-sectional diameter, true-lumen area, and false-lumen area over several follow-up examinations were derived., Conclusion: A segmentation pipeline was used to accurately identify true and false lumina on CT angiograms of aortic dissection. These segmentations can be used to obtain diameter and other morphologic parameters for surveillance and risk stratification. Supplemental material is available for this article. © RSNA, 2020., Competing Interests: Disclosures of Conflicts of Interest: L.D.H. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: is a paid consultant for Arterys. Other relationships: disclosed no relevant relationships. G.M. disclosed no relevant relationships. K.H. disclosed no relevant relationships. M.K. disclosed no relevant relationships. M.J.W. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: is a paid consultant for Arterys; has grants/grants pending from Philips Healthcare; has stock/stock options in Segmed. Other relationships: disclosed no relevant relationships. A.M.S. disclosed no relevant relationships. M.F. disclosed no relevant relationships. D.F. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: institution has grants/grants pending from Siemens; has stock/stock options in iSchemaView and Segmed. Other relationships: disclosed no relevant relationships., (2020 by the Radiological Society of North America, Inc.)

Purpose: Chronic kidney disease (CKD) is prevalent in transcatheter aortic valve replacement (TAVR) candidates, leading to concerns regarding contrast medium (CM) safety. We evaluated (a) the impact of low-CM imaging on pre-TAVR measurements and (b) postcontrast acute kidney injury (PC-AKI) prevalence after dual-source computed tomography (DSCT) in TAVR candidates., Methods: All TAVR candidates with CKD (SCr≥1.5 mg/dL) who underwent weight-based low-CM, low-pitch helical 3 rd -generation DSCT in a one-year period were included, and matched to standard-CM, non-CKD controls (N = 50). Image quality (IQ) and pre-TAVR measurement interobserver variability were evaluated. Renal function change and PC-AKI were studied in the entire TAVR cohort, irrespective of scan mode (N = 153)., Results: Low-CM in CKD (N = 25) was performed with median 68 mL CM [52-87], 90 kV [80-90] and SCr 1.6 mg/dL [1.5-1.9], and standard-CM without CKD with median 116 mL CM [96-134], 100 kV [90-110] and SCr 1.0 mg/dL [0.9-1.1](P < 0.00). Low-CM IQ was good, though lower compared with standard-CM (P < 0.02). Interobserver measurement reliability was excellent (ICCs>0.85). Interobserver-agreement was lower in low-CM, causing prosthesis size disagreement in 5/25 (kappa-0.73) versus 0/25 with standard-CM (kappa-1.00), and transfemoral eligibility disagreement in 4/25 (kappa-0.68) versus 2/25 (kappa-0.84), respectively. Mean 1-month SCr-change in the low-CM TAVR cohort (N = 35) was -1 % [-12 to +7 %] and in standard-CM (N = 118) 0 % [-8 to +10 %](P > 0.3). PC-AKI occurred in none., Conclusion: Low-CM third-generation-DSCT achieves good IQ in TAVR candidates with CKD, and seems safe, with no apparent renal function deterioration or prevalence of PC-AKI. However, standard-CM protocols in non-CKD patients provide higher measurement reproducibility. Low-CM protocols should therefore be reserved for patients at high risk for PC-AKI., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: To investigate the association of aortomitral continuity calcification (AMCC) with all-cause mortality, postprocedural paravalvular leak (PVL), and prolonged hospital stay in patients undergoing transcatheter aortic valve replacement (TAVR)., Materials and Methods: The authors retrospectively evaluated 329 patients who underwent TAVR between March 2013 and March 2016. AMCC, aortic valve calcification (AVC), and coronary artery calcification (CAC) were quantified by using preprocedural CT. Pre-procedural Society of Thoracic Surgeons (STS) score was recorded. Associations between baseline AMCC, AVC, and CAC and 1-year mortality, PVL, and hospital stay longer than 7 days were analyzed., Results: The median follow-up was 415 days (interquartiles, 344-727 days). After 1 year, 46 of the 329 patients (14%) died and 52 (16%) were hospitalized for more than 7 days. Of the 326 patients who underwent postprocedural echocardiography, 147 (45%) had postprocedural PVL. The CAC score (hazard ratio: 1.11 per 500 points) and AMCC mass (hazard ratio: 1.13 per 500 mg) were associated with 1-year mortality. AVC mass (odds ratio: 1.93 per 100 mg) was associated with postprocedural PVL. Only the STS score was associated with prolonged hospital stay (odds ratio: 1.19 per point)., Conclusion: AMCC is associated with mortality within 1 year after TAVR and substantially improves individual risk classification when added to a model consisting of STS score and AVC mass only. Supplemental material is available for this article. © RSNA, 2019See also the commentary by Brown and Leipsic in this issue., Competing Interests: Disclosures of Conflicts of Interest: M.J.W. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: is a paid consultant for Arterys; institution has grants/grants pending from Philips Healthcare; has stock/stock options in Segmed. Other relationships: disclosed no relevant relationships. E.M. disclosed no relevant relationships. K.J.M. disclosed no relevant relationships. J.B.K. disclosed no relevant relationships. F.H. disclosed no relevant relationships. Y.K. disclosed no relevant relationships. T.N. disclosed no relevant relationships. K.N. Activities related to the present article: institution received unrestricted research support from HeartFlow. Activities not related to the present article: received travel/accommodations/meeting expenses from HeartFlow; received unrestricted institutional research support from Siemens Healthineers and Bayer Healthcare. Other relationships: disclosed no relevant relationships. N.C. disclosed no relevant relationships. T.K. disclosed no relevant relationships. K.H. disclosed no relevant relationships. A.M.S. disclosed no relevant relationships. A.C.Y. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: institution has grants/grants pending from PARTNERS Study and Edwards. Other relationships: disclosed no relevant relationships. A.M.L. disclosed no relevant relationships. D.C.M. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: is a paid consultant for Medtronic; institution has grants/grants pending from Edwards Lifesciences and Medtronic. Other relationships: disclosed no relevant relationships. M.F. disclosed no relevant relationships. W.F.F. disclosed no relevant relationships. D.F. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: institution has grants/grants pending from Siemens; received payment for lectures including service on speakers bureaus from Bracco; has a patent pending; has stock in iSchemaView. Other relationships: disclosed no relevant relationships., (2019 by the Radiological Society of North America, Inc.)

High-sensitivity Troponin (hs-Tn) has emerged as a useful marker for patients with myocardial injury or heart failure. However, few studies have compared intermediate and hs-Tn in patients undergoing transcatheter aortic valve replacement (TAVR). Moreover, there remains uncertainty of which thresholds are the most useful for discriminating ventricular dysfunction or outcome. In this study we prospectively enrolled 105 patients with severe aortic stenosis (AS) who underwent TAVR as well as blood sampling for high-sensitivity (hs-TnI) and conventional troponin I (EXL-LOCI and RXL) assessment. Patients underwent comprehensive pre-procedure echocardiography. Ventricular dysfunction was defined using left ventricular mass index (LVMI), LV global longitudinal strain (LVGLS) and LV end-diastolic pressure. The mean age was 84.0 ± 8.7 years old and 60% were male sex with mean transaortic pressure gradient of 50.1 ± 16.0 mmHg and AVA of 0.63 ± 0.19 cm 2 . When using a threshold of 6 ng/L, 77% had positive hs-TnI while 27% had positive hs-TnI using recommended thresholds (16 ng/L for female and 34 ng/L for male). Troponin levels were higher in the presence of abnormal LV phenotypes. The strongest correlate of troponin was LVMI. During median follow-up of 375 days, 21 patients (20%) died. Lower threshold of hs-TnI and EXL-TnI was more discriminatory for overall mortality (Log-rank P = 0.03 for both), while higher threshold of hs-TnI (p = 0.75) and RXL-TnI were not (p = 0.30). Combining hs-TnI and BNP improved to predict long-term outcome (p = 0.004). In conclusion, hs-TnI levels correlated with the degree of LV dysfunction phenotypes. Furthermore, applying a lower threshold for hs-TnI performed better for outcome prediction than a recommended threshold in patients undergoing TAVR. Combining hs-TnI with BNP helped better risk stratification.

Objective: Previous studies have suggested that cytokines and growth factors may predict ventricular recovery following aortic valve replacement (AVR). The primary objective of this study was to identify cytokines that predict ventricular recovery following transcatheter AVR (TAVR)., Methods: We prospectively enrolled 121 consecutive patients who underwent TAVR. Standard echocardiographic assessment at baseline, 1-month and 1-year after TAVR included left ventricular (LV) mass index (LVMI) and global longitudinal strain (GLS). Blood samples were obtained at the time of the procedure to measure cytokines using a 63-plex Luminex platform. Partial least squares-discriminant analysis was performed to identify cytokines associated with ventricular remodeling and function at baseline as well as 1 year after TAVR., Results: The mean age was 84 ± 9 years, with a majority of male subjects (59%), a mean LVMI of 120.4 ± 45.1 g/m 2 and LVGLS of -13.0 ± 3.2%. On average, LV mass decreased by 8.1% and GLS improved by 20.3% at 1 year following TAVR. Among cytokines assayed, elevated hepatocyte growth factor (HGF) emerged as a common factor significantly associated with worse baseline LVMI and GLS as well as reduced ventricular recovery (p < 0.005). Other factors associated with ventricular recovery included a select group of vascular growth factors, inflammatory mediators and tumor necrosis factors, including VEGF-D, ICAM-1, TNFβ, and IL1β., Conclusion: We identified a network of cytokines, including HGF, that are significantly correlated with baseline LVMI and GLS, and ventricular recovery following TAVR., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Recent data suggest that circulating biomarkers may predict outcome in patients undergoing transcatheter aortic valve replacement (TAVR). We examined the association between inflammatory, myocardial, and renal biomarkers and their role in ventricular recovery and outcome after TAVR., Methods and Results: A total of 112 subjects undergoing TAVR were included in the prospective registry. Plasma levels of B-type natriuretic peptide, hs-TnI (high-sensitivity troponin I), CRP (C-reactive protein), GDF-15 (growth differentiation factor 15), GAL-3 (galectin-3), and Cys-C (cystatin-C) were assessed before TAVR and in 100 sex-matched healthy controls. Among echocardiographic parameters, we measured global longitudinal strain, indexed left ventricular mass, and indexed left atrial volume. The TAVR group included 59% male, with an average age of 84 years, and 1-year mortality of 18%. Among biomarkers, we found GDF-15 and CRP to be strongly associated with all-cause mortality ( P <0.001). Inclusion of GDF-15 and CRP to the Society of Thoracic Surgeons score significantly improved C index (0.65-0.79; P <0.05) and provided a category-free net reclassification improvement of 106% at 2 years ( P =0.01). Among survivors, functional recovery in global longitudinal strain (>15% improvement) and indexed left ventricular mass (>20% decrease) at 1 year occurred in 48% and 22%, respectively. On multivariate logistic regression, lower baseline GDF-15 was associated with improved global longitudinal strain at 1 year (hazard ratio=0.29; P <0.001). Furthermore, improvement in global longitudinal strain at 1 month correlated with lower overall mortality (hazard ratio=0.45; P =0.03)., Conclusions: Elevated GDF-15 correlates with lack of reverse remodeling and increased mortality after TAVR and improves risk prediction of mortality when added to the Society of Thoracic Surgeons score., (© 2017 American Heart Association, Inc.)

Valvulo-arterial impedance (Zva) has been shown to predict worse outcome in medically managed aortic stenosis (AS) patients. We aimed to investigate the association between Zva and left ventricular (LV) adaptation and to explore the predictive value of Zva for cardiac functional recovery and outcome after transcatheter aortic valve replacement (TAVR). We prospectively enrolled 128 patients with AS who underwent TAVR. Zva was calculated as: (systolic blood pressure + mean transaortic gradient)/stroke volume index). Echocardiographic assessment occurred at baseline, 1-month and 1-year after TAVR. The primary endpoints were to investigate associations between Zva and global longitudinal strain (GLS) at baseline as well as GLS change after TAVR. The secondary was to compare all-cause mortality after TAVR between patients with pre-defined Zva (=5 mmHg m 2 /ml), stroke volume index (=35 ml/m 2 ), and GLS (=-15%) cutoffs. The mean GLS was reduced (-13.0 ± 3.2%). The mean Zva was 5.2 ± 1.6 mmHg*m 2 /ml with 55% of values ≥5.0 mmHg*m 2 /ml, considered to be abnormally high. Higher Zva correlated with worse GLS (r = -0.33, p < 0.001). After TAVR, Zva decreased significantly (5.1 ± 1.6 vs. 4.5 ± 1.6 mmHg*m 2 /ml, p = 0.001). A reduction of Zva at 1-month was associated with GLS improvement at 1-month (r = -0.31, p = 0.001) and at 1-year (r = -0.36 and p = 0.001). By Kaplan-Meier analysis, patients with higher Zva at baseline had higher mortality (Log-rank p = 0.046), while stroke volume index and GLS did not differentiate outcome (Log-rank p = 0.09 and 0.25, respectively). As a conclusion, Zva is correlated with GLS in AS as well as GLS improvement after TAVR. Furthermore, a high baseline Zva may have an additional impact to traditional parameters on predicting worse mortality after TAVR.

Macrophages are cellular mediators of vascular inflammation and are involved in the formation of atherosclerotic plaques. These immune cells secrete proteases such as matrix metalloproteinases and cathepsins that contribute to disease formation and progression. Here, we demonstrate that activity-based probes (ABPs) targeting cysteine cathepsins can be used in murine models of atherosclerosis to noninvasively image activated macrophage populations using both optical and PET/CT methods. The probes can also be used to topically label human carotid plaques demonstrating similar specific labeling of activated macrophage populations., Methods: Macrophage-rich carotid lesions were induced in FVB mice fed on a high-fat diet by streptozotocin injection followed by ligation of the left common carotid artery. Mice with carotid atherosclerotic plaques were injected with the optical or dual-modality probes BMV109 and BMV101, respectively, via the tail vein and noninvasively imaged by optical and small-animal PET/CT at different time points. After noninvasive imaging, the murine carotid arteries were imaged in situ and ex vivo, followed by immunofluorescence staining to confirm target labeling. Additionally, human carotid plaques were topically labeled with the probe and analyzed by both sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunofluorescence staining to confirm the primary targets of the probe., Results: Quantitative analysis of the signal intensity from both optical and PET/CT imaging showed significantly higher levels of accumulation of BMV109 and BMV101 (P < 0.005 and P < 0.05, respectively) in the ligated left carotid arteries than the right carotid or healthy arteries. Immunofluorescence staining for macrophages in cross-sectional slices of the murine artery demonstrated substantial infiltration of macrophages in the neointima and adventitia of the ligated left carotid arteries compared with the right. Analysis of the human plaque tissues by sodium dodecyl sulfate polyacrylamide gel electrophoresis confirmed that the primary targets of the probe were cathepsins X, B, S, and L. Immunofluorescence labeling of the human tissue with the probe demonstrated colocalization of the probe with CD68, elastin, and cathepsin S, similar to that observed in the experimental carotid inflammation murine model., Conclusion: We demonstrate that ABPs targeting the cysteine cathepsins can be used in murine models of atherosclerosis to noninvasively image activated macrophage populations using both optical and PET/CT methods. The probes could also be used to topically label human carotid plaques demonstrating similar specific labeling of activated macrophage populations. Therefore, ABPs targeting the cysteine cathepsins are potentially valuable new reagents for rapid and noninvasive imaging of atherosclerotic disease progression and plaque vulnerability., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Objectives: The logistic European System for Cardiac Operative Risk Evaluation (LES) score and the Society of Thoracic Surgeons (STS) score are validated to predict 30-day outcomes following surgical aortic valve replacement (SAVR) with or without coronary artery bypass grafting. Their performance when applied to patients undergoing transcatheter aortic valve replacement (TAVR) is controversial., Methods: We compared predicted and observed 30-day/in-hospital and 1-year mortality of patients undergoing TAVR in the first Placement of Aortic Transcatheter Valves trial and continued access registry (N = 2466). The performance of the LES and STS scores (prospectively calculated) was evaluated using standard assessments of discrimination and calibration. Performance of STS and LES scores among 307 patients undergoing SAVR from the high-risk cohort of the randomized trial were also examined., Results: In patients undergoing TAVR, the observed 30-day/in-hospital mortality was 6.5%, whereas the predicted 30-day mortality was higher by both STS score (11.4% ± 3.9%) and LES score (26.6% ± 16.2%). The discrimination for both scores was poor for 30-day/in-hospital and 1-year mortality. Calibration was better for STS score than for LES at 1 year but poor for both at 30 days among TAVR cohort. These results were consistent among the subgroups of patients undergoing transfemoral and transapical access; however, the STS score had better performance among the high-risk patients who underwent SAVR at 30 days but not 1 year., Conclusions: The STS and LES surgical risk scores overestimated 30-day/in-hospital mortality and were poor discriminators of post-TAVR mortality, but the calibration of the STS score was better in these high-risk patients. These data highlight the need for TAVR-specific risk models to optimize patient selection., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background and Aim of the Study: Aortic aneurysm size is known to portend a higher likelihood of aortic complications in patients with connective tissue disorders (CTD), but other objective tools are needed to determine which patients are at greatest risk of dissection, especially those which reflect the structural integrity and strength of the aortic wall., Methods: The aortic wall pathology was evaluated in CTD patients with and without acute aortic dissection to identify parameters that affect the risk of dissection. A retrospective review was performed of aneurysm pathology from patients with Marfan syndrome (MFS; n = 53) without dissection undergoing prophylactic aortic root surgery, and acute type A aortic dissection patients (AAAoD; n = 16). Patients without a cardiovascular cause of death (n = 19) served as controls. The minimal aortic medial wall thickness was measured, and medial myxoid degeneration (MMD) and the degree of elastin loss and fragmentation were graded., Results: The mean minimal aortic wall thickness was 1,625 +/- 364 microm in controls, and 703 +/- 256 microm and 438 +/- 322 microm for MFS and AAAoD patients, respectively. Aortic root diameters did not correlate with aortic wall thickness. A comparison of aortic medial thickness showed that the media was significantly thinner among acute dissection patients than either elective surgical patients (p = 0.02) or controls (p < 0.001). Aortic size, degree of MMD, and elastin loss did not vary significantly between CTD patients., Conclusion: A diminished aortic wall medial thickness may be linked to aortic dissection. High-resolution imaging techniques in the future may lead to the morphological assessment of aortic medial wall thickness in vivo becoming a reality which, in theory, could provide a more refined risk prognostication for acute aortic dissection.

Background: The Placement of Aortic Transcatheter Valves (PARTNER) trial showed that among high-risk patients with aortic stenosis, the 1-year survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical replacement. However, longer-term follow-up is necessary to determine whether TAVR has prolonged benefits., Methods: At 25 centers, we randomly assigned 699 high-risk patients with severe aortic stenosis to undergo either surgical aortic-valve replacement or TAVR. All patients were followed for at least 2 years, with assessment of clinical outcomes and echocardiographic evaluation., Results: The rates of death from any cause were similar in the TAVR and surgery groups (hazard ratio with TAVR, 0.90; 95% confidence interval [CI], 0.71 to 1.15; P=0.41) and at 2 years (Kaplan-Meier analysis) were 33.9% in the TAVR group and 35.0% in the surgery group (P=0.78). The frequency of all strokes during follow-up did not differ significantly between the two groups (hazard ratio, 1.22; 95% CI, 0.67 to 2.23; P=0.52). At 30 days, strokes were more frequent with TAVR than with surgical replacement (4.6% vs. 2.4%, P=0.12); subsequently, there were 8 additional strokes in the TAVR group and 12 in the surgery group. Improvement in valve areas was similar with TAVR and surgical replacement and was maintained for 2 years. Paravalvular regurgitation was more frequent after TAVR (P<0.001), and even mild paravalvular regurgitation was associated with increased late mortality (P<0.001)., Conclusions: A 2-year follow-up of patients in the PARTNER trial supports TAVR as an alternative to surgery in high-risk patients. The two treatments were similar with respect to mortality, reduction in symptoms, and improved valve hemodynamics, but paravalvular regurgitation was more frequent after TAVR and was associated with increased late mortality. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.).

Objective: Cell therapy is an exciting area of investigation for repair of injured myocardial tissue. Platelet-rich plasma (PRP) is an autologous fractionation of whole blood containing high concentrations of growth factors including vascular endothelial growth factor and insulin-like growth factor, among many others. PRP has been shown to safely and effectively enhance healing of musculoskeletal tissue primarily by reparative cell signaling. Despite a growing body of evidence on PRP's safety and efficacy, limited studies have been performed using PRP in cardiovascular tissues. Utilizing a murine myocardial permanent ligation and ischemia/reperfusion model, this study sought to determine whether RevaTen PRP (Menlo Park, CA, USA), a proprietary formulation of PRP, improves cardiac function as measured by left ventricular ejection fraction (LVEF)., Methods: Via thoracotomy, the left anterior descending arteries (LAD) of 28 mice were occluded by suture either permanently or for 45 min to induce ischemic injury and then reperfused. Mice undergoing permanent ligation had intramyocardial injections of either RevaTen PRP (n=5) or phosphate-buffered saline (PBS; n=4). Magnetic resonance (MR) imaging was performed to calculate LVEF at 7 days. Mice undergoing ischemia and reperfusion had intramyocardial injections of either PRP (n=10) or PBS (n=9) and underwent MR imaging to calculate LVEF at 21 days. Hearts were harvested for histologic examination following imaging., Results: Compared with PBS controls, RevaTen PRP-treated animals that underwent LAD ligation had a 38% higher LVEF 7 days after injury (PRP=36.1±6.1%; PBS=26.4±3.6%, P=.027). Compared with PBS controls, PRP-treated animals who underwent ischemia-reperfusion of the LAD had a 28% higher LVEF 21 days after injury (PRP=37.6±4.8%, control=29.3±9.7%, P=.038). Histologic analysis suggested the presence of more scar tissue in the control group compared to the PRP-treated animals., Conclusion: MR imaging demonstrated a positive effect of RevaTen PRP on left ventricular function in both a ligation and ischemia-reperfusion murine model. Our results suggest RevaTen PRP should be investigated further as a potential point-of-care biologic treatment following myocardial injury., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Although the optimal surgical treatment of the dilated aortic arch is controversial in patients with a bicuspid aortic valve, such exists in more than 70% of bicuspid aortic valve patients. Aortic wall histologic abnormalities are present from the aortic root to the distal arch regardless of aortic size. We describe a simple "peninsula-style" technique of transverse arch replacement used in conjunction with valve-sparing aortic root replacement for patients with a bicuspid aortic valve. This provides resection of the entire dilated thoracic aorta, preserving the arch branches in continuity with the proximal descending aorta., (Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to assess the efficacy of FK778 to prevent acute and chronic allograft rejection compared with other immunosuppressive agents., Materials and Methods: Heterotopic Brown-Norway (BN)-to-Lewis rat cardiac transplantations and heterotopic BN-to-Lewis tracheal transplantations were performed to study acute heart rejection and the development of chronic obliterative airway disease (OAD), respectively. Recipients were treated with FK778, tacrolimus, MMF, or sirolimus for 10 days (acute rejection study) or 28 days (chronic OAD study) at varying doses., Results: In untreated recipients, cardiac allograft survival was 6.2 +/- 0.4 days. FK778 (20 mg/kg), tacrolimus (2 or 8 mg/kg), mycophenolate mofetil (MMF; 40 mg/kg), or sirolimus (0.5 or 2 mg/kg) significantly prolonged graft survival to 17.0 +/- 2.8, 18.5 +/- 2.7, 25.0 +/- 2.5, 20.7 +/- 3.8, 14.5 +/- 2.2, and 23.2 +/- 1.5 days, respectively (P < .05). Tracheal grafts in untreated recipients showed intense infiltration and complete luminal obliteration by day 28. FK778 (20 mg/kg), tacrolimus (1 or 4 mg/kg), MMF (10 or 40 mg/kg), or sirolimus (0.5 or 2 mg/kg) significantly inhibited tracheal luminal obliteration (19.5% +/- 16.4%, 44.2% +/- 33.6%, 12.3% +/- 3.3%, 61.7% +/- 18.6%, 18.3% +/- 11.3%, 55.0% +/- 30.9%, and 8.5% +/- 3.5% (P < .05). All 4 high-dose groups showed similar efficacy., Conclusions: When used in therapeutic doses, tacrolimus and sirolimus were more effective than FK778 to prolong cardiac allograft survival. However, with its antiproliferative effects on smooth muscle cells, its good tolerability, and its blockade of cytomegalovirus replication, FK778 proved effective to prevent chronic OAD development. Thus, FK778 may acquire an important role in maintenance therapy for the prevention of long-term fibroproliferative complications.