Late Outcomes of Surgery Versus Medical Therapy in Patients With Type A Aortic Intramural Hematoma: Meta-Analysis of Reconstructed Time-to-Event Data.

The effect of an initial surgical approach (in comparison with initial medical therapy) in acute type A intramural hematoma remains insufficiently explored. We designed a pooled analysis of Kaplan-Meier-derived individual patient data from studies with follow-up for overall survival (all-cause death). Restricted mean survival time was calculated to evaluate lifetime gain or loss. The Risk of Bias in Non-Randomized Studies of Interventions tool (ROBINS-I) was used to assess risk of bias. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was applied to assess certainty of evidence. Eight studies met our eligibility criteria, including a total of 654 patients (311 patients treated with surgery and 343 patients treated with medical therapy alone). All the studies were non-randomized and observational. The median follow-up was 4.6 years (interquartile range 1.0 to 7.7). Patients who underwent surgery had a significantly lower risk of mortality compared with patients receiving medical therapy alone (hazard ratio 0.51, 95% confidence interval 0.35 to 0.74, p <0.001). The restricted mean survival time was overall 1.1 years greater with surgery compared with medical therapy, and this difference was statistically significant (p <0.001), which means that surgery is associated with lifetime gain. The overall risk of bias (ROBINS-I) was considered moderate-to-serious and the certainty of evidence (GRADE) was deemed to be low. In conclusion, in the overall follow-up, surgery as the initial approach was associated with better late survival and lifetime gain in comparison with medical therapy alone in the setting of acute type A aortic intramural hematoma; however, high-quality randomized trials are warranted to establish the efficacy of the surgical strategy.

Paradoxical Changes: EMMPRIN Tissue and Plasma Levels in Marfan Syndrome-Related Thoracic Aortic Aneurysms.

Background: Thoracic aortic aneurysms (TAAs) associated with Marfan syndrome (MFS) are unique in that extracellular matrix metalloproteinase inducer (EMMPRIN) levels do not behave the way they do in other cardiovascular pathologies. EMMPRIN is shed into the circulation through the secretion of extracellular vesicles. This has been demonstrated to be dependent upon the Membrane Type-1 MMP (MT1-MMP). We investigated this relationship in MFS TAA tissue and plasma to discern why unique profiles may exist. Methods: Protein targets were measured in aortic tissue and plasma from MFS patients with TAAs and were compared to healthy controls. The abundance and location of MT1-MMP was modified in aortic fibroblasts and secreted EMMPRIN was measured in conditioned culture media. Results: EMMPRIN levels were elevated in MFS TAA tissue but reduced in plasma, compared to the controls. Tissue EMMPRIN elevation did not induce MMP-3, MMP-8, or TIMP-1 expression, while MT1-MMP and TIMP-2 were elevated. MMP-2 and MMP-9 were reduced in TAA tissue but increased in plasma. In aortic fibroblasts, EMMPRIN secretion required the internalization of MT1-MMP. Conclusions: In MFS, impaired EMMPRIN secretion likely contributes to higher tissue levels, influenced by MT1-MMP cellular localization. Low EMMPRIN levels, in conjunction with other MMP analytes, distinguished MFS TAAs from controls, suggesting diagnostic potential.

New Directions in Diagnostics for Aortic Aneurysms: Biomarkers and Machine Learning.

This review article presents an appraisal of pioneering technologies poised to revolutionize the diagnosis and management of aortic aneurysm disease, with a primary focus on the thoracic aorta while encompassing insights into abdominal manifestations. Our comprehensive analysis is rooted in an exhaustive survey of contemporary and historical research, delving into the realms of machine learning (ML) and computer-assisted diagnostics. This overview draws heavily upon relevant studies, including Siemens' published field report and many peer-reviewed publications. At the core of our survey lies an in-depth examination of ML-driven diagnostic advancements, dissecting an array of algorithmic suites to unveil the foundational concepts anchoring computer-assisted diagnostics and medical image processing. Our review extends to a discussion of circulating biomarkers, synthesizing insights gleaned from our prior research endeavors alongside contemporary studies gathered from the PubMed Central database. We elucidate the prevalent challenges and envisage the potential fusion of AI-guided aortic measurements and sophisticated ML frameworks with the computational analyses of pertinent biomarkers. By framing current scientific insights, we contemplate the transformative prospect of translating fundamental research into practical diagnostic tools. This narrative not only illuminates present strides, but also forecasts promising trajectories in the clinical evaluation and therapeutic management of aortic aneurysm disease.

Mechanical pump complication after HeartMate 3 implantation.

BACKGROUND: With the improvement in postoperative complications and long-term survival post LVAD, continuing to improve clinical outcomes will require efforts to decrease long-term complications. The purpose of this study is to describe the incidence of mechanical pump failure requiring surgery, which we define as pump failure secondary to either outflow graft compression, outflow graft obstruction, or pump thrombosis requiring surgical intervention. METHODS: 141 consecutive adult patients who underwent HeartMate3 Implantation using the "cut-then-sew" implantation technique between September 2015 and September 2021 were included in our study. The primary outcome measure was mechanical pump complication (outflow graft obstruction and or pump thrombosis) requiring surgical intervention. Secondary outcome measures included incidence of bleeding, stroke, renal failure, length of stay, and overall survival. Median follow up was 27.3 months. RESULTS: Eleven (7.8%) of patients developed mechanical pump complications. Six patients developed outflow graft obstruction. Five patients developed acute pump thrombosis. Median time to a mechanical complication was 828 days. Of the 11 patients who underwent surgery, 10 patients (90%) survived to discharge. Overall survival at 1, 3, and 5 years was 82.9%, 69.1% and 55.2% respectively for the entire cohort. CONCLUSION: The mechanical pump complication rate of 7.8% which is quite high may be related to duration of follow up, as the median time to mechanical complication was 828 days. This study highlights an important late complication that occurs post LVAD implantation.

Long-Term Outcomes of Patients Undergoing Aortic Root Replacement With Mechanical Versus Bioprosthetic Valves: Meta-Analysis of Reconstructed Time-to-Event Data.

Background An aspect not so clear in the scenario of aortic surgery is how patients fare after composite aortic valve graft replacement (CAVGR) depending on the type of valve (bioprosthetic versus mechanical). We performed a study to evaluate the long-term outcomes of both strategies comparatively. Methods and Results Pooled meta-analysis of Kaplan-Meier-derived time-to-event data from studies with follow-up for overall survival (all-cause death), event-free survival (composite end point of cardiac death, valve-related complications, stroke, bleeding, embolic events, and/or endocarditis), and freedom from reintervention. Twenty-three studies met our eligibility criteria, including 11 428 patients (3786 patients with mechanical valves and 7642 patients with bioprosthetic valve). The overall population was mostly composed of men (mean age, 45.5-75.6 years). In comparison with patients who underwent CAVGR with bioprosthetic valves, patients undergoing CAVGR with mechanical valves presented no statistically significant difference in the risk of all-cause death in the first 30 days after the procedure (hazard ratio [HR], 1.24 [95% CI, 0.95-1.60]; P=0.109), but they had a significantly lower risk of all-cause mortality after the 30-day time point (HR, 0.89 [95% CI, 0.81-0.99]; P=0.039) and lower risk of reintervention (HR, 0.33 [95% CI, 0.24-0.45]; P<0.001). Despite its increased risk for the composite end point in the first 6 years of follow-up (HR, 1.41 [95% CI, 1.09-1.82]; P=0.009), CAVGR with mechanical valves is associated with a lower risk for the composite end point after the 6-year time point (HR, 0.46 [95% CI, 0.31-0.67]; P<0.001). Conclusions CAVGR with mechanical valves is associated with better long-term outcomes in comparison with CAVGR with bioprosthetic valves.

Long-term outcomes of valve-sparing root versus composite valve graft replacement for acute type A aortic dissection: Meta-analysis of reconstructed time-to-event data.

OBJECTIVES: To evaluate the long-term outcomes of valve-sparing aortic root replacement (VSARR) versus composite aortic valve graft replacement (CAVGR) in the treatment of acute type A aortic dissections (ATAAD). METHODS: We performed a pooled meta-analysis of Kaplan-Meier-derived time-to-event data from studies with longer follow-up beyond the immediate postoperative period. RESULTS: Seven studies met our eligibility criteria, comprising a total of 858 patients (367 patients in the VSARR groups and 491 patients in the CAVGR group). We found no statistically significant differences in the overall survival between the groups over time (HR 0.83, 95%CI 0.63-1.10, P = 0.192), but we observed a higher risk of reoperation in the VSARR group when compared with the CAVGR group (HR 9.99, 95% CI 2.23-44.73, P = 0.003). The meta-regression revealed statistically significant positive coefficients for age (P < 0.001) in the analysis of survival, which means that this covariate has a modulating effect on this outcome. The higher the mean age, the higher the HR for overall mortality was found to be with VSARR as compared with CAVGR. Other covariates such as female sex, hypertension, diabetes, connective tissue disorders, bicuspid aortic valve, hemiarch and/or total arch replacement, concomitant coronary bypass surgery did not seem to have any effect on the outcomes. CONCLUSION: VSARR did not confer a better (or worse) survival over time in patients with ATAAD, but it was associated with higher risk of reoperations in the long run.

A standardized method for plasma extracellular vesicle isolation and size distribution analysis.

The following protocol describes our workflow for isolation and quantification of plasma extracellular vesicles (EVs). It requires limited sample volume so that the scientific value of specimens is maximized. These steps include isolation of vesicles by automated size exclusion chromatography and quantification by tunable resistive pulse sensing. This workflow optimizes reproducibility by minimizing variations in processing, handling, and storage of EVs. EVs have significant diagnostic and therapeutic potential, but clinical application is limited by disparate methods of data collection. This standardized protocol is scalable and ensures efficient recovery of physiologically intact EVs that may be used in a variety of downstream biochemical and functional analyses. Simultaneous measurement quantifies EV concentration and size distribution absolutely. Absolute quantification corrects for variations in EV number and size, offering a novel method of standardization in downstream applications.

Unilateral versus bilateral anterograde cerebral perfusion in acute type A aortic dissection repair: A systematic review and meta-analysis.

OBJECTIVES: The aim of the study is to compare the safety and efficacy of unilateral anterograde cerebral perfusion (UACP) and bilateral anterograde cerebral perfusion (BACP) for acute type A aortic dissection (ATAAD). METHODS: A systematic review of the MEDLINE (PubMed), Scopus, and Cochrane Library databases (last search: August 7th, 2021) was performed according to the PRISMA statement. Studies directly comparing UACP versus BACP for ATAAD were included. Random-effects meta-analyses were performed. RESULTS: Eight retrospective cohort studies were identified, incorporating 2416 patients (UACP: 843, BACP: 1573). No statistically significant difference was observed regarding in-hospital mortality (odds ratio [OR]:1.05 [95% Confidence Interval (95% CI):0.70-1.57]), permanent neurological deficit (PND) (OR: 0.94 [95% CI: 0.52-1.70]), transient neurological deficit (TND) (OR: 1.37 [95% CI: 0.98-1.92]), renal failure (OR: 0.96 [95% CI: 0.70-1.32]), and re-exploration for bleeding (OR: 0.77 [95% CI: 0.48-1.22]). Meta-regression analysis revealed that PND and TND were not influenced by differences in rates of total arch repair, Bentall procedure, and concomitant CABG in UACP and BACP groups. Cardiopulmonary bypass time (Standard Mean Difference [SMD]: -0.11 [95% CI: -0.22, 0.44]), Cross clamp time (SMD: -0.04 [95% CI: -0.38, 0.29]), and hypothermic circulatory arrest time (SMD: -0.12 [95% CI: -0.55, 0.30]) were comparable between UACP and BACP. Intensive care unit stay was shorter in BACP arm (SMD:0.16 [95% CI: 0.01, 0.31]); however, length of hospital stay was shorter in UACP arm (SMD: -0.25 [95% CI: -0.45, -0.06]). CONCLUSIONS: UACP and BACP had similar results in terms of in-hospital mortality, PND, TND, renal failure, and re-exploration for bleeding rate in patients with ATAAD. ICU stay was shorter in the BACP arm while LOS was shorter in the UACP arm.

Plasma microrna quantification protocol.

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate translation and are involved in many pathological processes. They have emerged as promising biomarkers for diagnosis of conditions such as aortic aneurysm disease. Quantifying miRNAs in plasma is uniquely challenging because of the lack of standardized reproducible protocols. To facilitate the independent verification of conclusions, it is necessary to provide a thorough disclosure of all pertinent experimental details. In this technical note, we present a comprehensive protocol for quantifying plasma miRNAs using droplet digital PCR. We detail the entire workflow, including blood collection, plasma processing, cryo-storage, miRNA isolation, reverse transcription, droplet generation, PCR amplification, fluorescence reading, and data analysis. We offer comprehensive guidance regarding optimization, assay conditions, expected results, and insight into the troubleshooting of common issues. The stepwise normalization and detailed methodological guide enhance reproducibility. Moreover, multiple portions of this protocol may be automated. The data provided in this technical note is demonstrative of the values typically obtained when following its steps. To facilitate standardization in data reporting, we include a table of expected aortic aneurysm-related miRNA levels in healthy human plasma. This versatile protocol can be easily adapted to quantify most circulating miRNAs in plasma, making it a valuable resource for diagnostic development.

Temporal Trends in Internal vs. External Referrals for TAVR in a Large Academic Center: Patients Characteristics and Outcomes.

Background: Since transcatheter aortic valve replacement (TAVR) first became approved for inoperable patients followed by high, intermediate-, and low-risk patients, referrals to TAVR centers have rapidly increased. The purpose of this study was to investigate referral patterns to a large academic TAVR center in the state of North Carolina and evaluate differences between externally and internally referred patients. Methods: Data for all patients who underwent TAVR at our institution between November 2014 and March 2020 were pulled from the Transcatheter Valve Therapy Registry. The electronic medical record was used to determine the referral source. The descriptive statistical analysis was performed using Excel (Microsoft, Redmond, Washington). Results: 491 patients underwent TAVR at our institution between November 2014 and March 2020. Half of the patients were referred by a cardiologist within the same health system (N = 250, 50.9%). Other referral sources included a cardiologist external to the health system (N = 210, N = 42.8%) and a surgeon or proceduralist (such as urologist, surgeon, or gastroenterologist) during the workup for another procedure (N = 26, 5.3%). Over time, there was a trend toward an increasing proportion of patients referred by a cardiologist external to our system, but this trend did not reach statistical significance (20.0% in 2014, 29.2% in 2015, 30.7% in 2016, 53.0% in 2017, 36% in 2018, 48.4% in 2019, and 56.8% in 2020, p=0.06 using the Mann-Kendall trend test). Externally referred patients were less likely to have private insurance and were more likely to have a reduced ejection fraction and had a higher mean gradient across the valve. Postprocedure, externally referred patients were more likely to have the procedure under moderate sedation and less likely to be discharged home. Conclusions: This study presents the referral pattern to a large TAVR center in North Carolina. Over time, there was an increase in external referrals suggesting that TAVR is increasingly adopted as an important component of the management of aortic valve stenosis. Internally and externally referred patients have differences in baseline demographic and clinical characteristics which may have an impact on clinical outcomes.

Peptide Amphiphile Supramolecular Nanofibers Designed to Target Abdominal Aortic Aneurysms.

An abdominal aortic aneurysm (AAA) is a localized dilation of the aorta located in the abdomen that poses a severe risk of death when ruptured. The cause of AAA is not fully understood, but degradation of medial elastin due to elastolytic matrix metalloproteinases is a key step leading to aortic dilation. Current therapeutic interventions are limited to surgical repair to prevent catastrophic rupture. Here, we report the development of injectable supramolecular nanofibers using peptide amphiphile molecules designed to localize to AAA by targeting fragmented elastin, matrix metalloproteinase 2 (MMP-2), and membrane type 1 matrix metalloproteinase. We designed four targeting peptide sequences from X-ray crystallographic data and incorporated them into PA molecules via solid phase peptide synthesis. After coassembling targeted and diluent PAs at different molar ratios, we assessed their ability to form nanofibers using transmission electron microscopy and to localize to AAA in male and female Sprague-Dawley rats using light sheet fluorescence microscopy. We found that three formulations of the PA nanofibers were able to localize to AAA tissue, but the MMP-2 targeting PA substantially outperformed the other nanofibers. Additionally, we demonstrated that the MMP-2 targeting PA nanofibers had an optimal dose of 5 mg (∼12 mg/kg). Our results show that there was not a significant difference in targeting between male and female Sprague-Dawley rats. Given the ability of the MMP-2 targeting PA nanofiber to localize to AAA tissue, future studies will investigate potential diagnostic and targeted drug delivery applications for AAA.

Mechanical versus bioprosthetic valve for aortic valve replacement: systematic review and meta-analysis of reconstructed individual participant data.

OBJECTIVES: The aim of this study was to compare biological versus mechanical aortic valve replacement. METHODS: We searched MEDLINE, Scopus and Cochrane Library databases for randomized clinical trials and propensity score-matched studies published by 14 October 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Individual patient data on overall survival were extracted. One- and two-stage survival analyses and random-effects meta-analyses were conducted. RESULTS: A total of 25 studies were identified, incorporating 8721 bioprosthetic and 8962 mechanical valves. In the one-stage meta-analysis, mechanical valves cumulatively demonstrated decreased hazard for mortality [hazard ratio (HR): 0.79, 95% confidence interval (CI): 0.74-0.84, P < 0.0001]. Overall survival was similar between the compared arms for patients <50 years old (HR: 0.88, 95% CI: 0.71-1.1, P = 0.216), increased in the mechanical valve arm for patients 50-70 years old (HR: 0.76, 95% CI: 0.70-0.83, P < 0.0001) and increased in the bioprosthetic arm for patients >70 years old (HR: 1.35, 95% CI: 1.17-1.57, P < 0.0001). Meta-regression analysis revealed that the survival in the 50-70 year-old group was not influenced by the publication year of the individual studies. No statistically significant difference was observed regarding in-hospital mortality, postoperative strokes and postoperative reoperation. All-cause mortality was found decreased in the mechanical group, cardiac mortality was comparable between the 2 groups, major bleeding rates were increased in the mechanical valve group and reoperation rates were increased in the bioprosthetic valve group. CONCLUSIONS: Survival rates seem to not be influenced by the type of prosthesis in patients <50 years old. The survival advantage in favour of mechanical valves is observed in patients 50-70 years old, while in patients >70 years old bioprosthetic valves offer better survival outcomes.

2020 Women in Thoracic Surgery Update on the Status of Women in Cardiothoracic Surgery.

BACKGROUND: Women in Thoracic Surgery (WTS) has previously reported on the status of women in cardiothoracic (CT) surgery. We sought to provide a 10-year update on women in CT surgery. METHODS: An anonymous research electronic data capture survey link was emailed to female diplomats of the American Board of Thoracic Surgery. Survey questions queried respondents regarding demographics, training, accolades, practice details, and career satisfaction. The survey link was open for 30 days. Results were compared with The Society of Thoracic Surgeons 2019 workforce survey. Descriptive analyses were performed using frequency and proportions. Comparisons were performed using Student's t tests, Fisher's exact tests, and χ2 tests. RESULTS: Of 354 female diplomats, 309 were contacted and 176 (57%) responded. The majority of respondents were aged 36 to 50 years (59%), white (67.4%), and had graduated from traditional-track programs (91.4%). Most respondents reported practicing in an urban (64%) and academic setting (73.1%). 36.4% and 23.9% reported a general thoracic and adult cardiac practice (22.7% mixed practice, 9.6% congenital). Fifty percent of respondents reported salaries between $400,000 and $700,000 annually; 37.7% reported salaries less than 90% of their male colleagues; 21.6% of respondents in academia are full professor; 53.4% reported having a leadership role. Whereas 74.1% would pursue a career in CT surgery again, only 27.3% agreed that CT surgery is a healthy and positive environment for women. CONCLUSIONS: The number of women in CT surgery has steadily increased. Although women are rising in academic rank and into leadership positions, salary disparities and the CT surgery work environment remain important issues in achieving a diverse work force.