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There are fewer than 100 reported cases of congenital left main coronary artery atresia. In this report, we present an adolescent male presenting with exertional syncope in the setting of this rare coronary defect, and review important diagnostic and therapeutic considerations imperative to obtain a favorable outcome., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: There is little evidence regarding the most beneficial choice between a mechanical and a bioprosthetic valve in the aortic position in dialysis patients. This meta-analysis compares the survival and freedom from reintervention rates between mechanical and bioprosthetic valves in patients on dialysis undergoing aortic valve replacement surgery., Methods: Two databases were searched, and the systematic review was performed in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. We conducted one-stage and two-stage meta-analysis with Kaplan-Meier-derived individual patient data and meta-analysis with random-effects model., Results: Eight studies were included, providing data about 1215 dialysis patients receiving mechanical valves and 1851 patients receiving bioprosthetic valves. During a mean follow-up of 43.1 months, overall survival rates were significantly improved in the mechanical valve group in comparison to the bioprosthetic one (hazard ratio [HR]: 0.76, 95% confidence interval [CI]: 0.69-0.84, p < 0.001). This was confirmed by the two-stage meta-analysis (HR: 0.72, 95% CI: 0.62-0.83, p = 0.00, I 2 = 17.79%). Regarding freedom from reintervention, no arm offered a statistically significant advantage, according to the two-stage generated analysis (HR: 1.025, 95% CI: 0.65-1.61, p = 0.914). Similarly, there was no evident superiority of a valve type for perioperative outcomes., Conclusions: Mechanical valves are likely to be associated with a better survival outcome compared to bioprosthetic valves for patients on dialysis undergoing aortic valve replacement. However, freedom from reoperation rates and perioperative outcomes were comparable between the two valve types, with no arm exhibiting a statistically significant advantage., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Chemotherapy-induced cardiotoxicity with subsequent heart failure (HF) is a major cause of morbidity and mortality in cancer survivors worldwide. Chemotherapy-induced HF is exceptionally challenging as it generally manifests in patients who are typically not eligible for left ventricular device implantation or heart transplantation. To explore alternative treatment strategies for cancer survivors suffering from chemotherapy-induced HF, we developed a minimally invasive infusible cardiac stromal cell secretomes adhesive (MISA) that could be delivered locally through an endoscope-guided intrapericardial injection. To mimic the typical clinical presentation of chemotherapy-induced HF in elder patients, we established an aged rat model in which restrictive cardiomyopathy with sequential HF was induced via consecutive doxorubicin injections. In vitro, we prove that MISA not only enhanced cardiomyocytes proliferation potency and viability, but also inhibited their apoptosis. In vivo, we prove that MISA improved the ventricular contractility indexes and led to beneficial effects on histological and structural features of restrictive cardiomyopathy via promoting cardiomyocyte proliferation, angiogenesis, and mitochondrial respiration. Additionally, we also evaluated the safety and feasibility of MISA intrapericardial delivery in a healthy porcine model with an intact immune system. In general, our data indicates that MISA has a strong potential for translation into large animal models and ultimately clinical applications for chemotherapy-induced HF prior to the final option of heart transplantation., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Authors.)

The large incisions and long recovery periods that accompany traditional cardiac surgery procedures along with the constant patient demand for minimally invasive procedures have motivated cardiac surgeons to implement the robotic technologies in their armamentarium. The robotic systems have been utilized successfully in various cardiac procedures including atrial septal defect repair, left atrial myxoma resection, MAZE procedure and left ventricular lead placement, yet coronary artery bypass and mitral valve repair still comprise the vast majority of them. This review analyzes the development of the robot-assisted cardiac surgery in recent years, its outcomes, advantages, disadvantages, its patient selection criteria as well as its economic feasibility. Robotic endovascular surgery, albeit its limited applications, is presently considered an attractive alternative to conventional endovascular approaches. The increased flexibility and precision along with the wider range of accessible anatomy provided by the endovascular robotic systems, have increased the pool of patients that can be offered minimally invasive treatment options and have helped to overcome many limitations of the traditional endovascular procedures. With this review we aimed to summarize the applications of the commercially available endovascular robotic devices, as well as the limitations and the future perspectives in the field of endovascular robotic surgery., (Copyright © 2022. Published by Elsevier Inc.)

Competing Interests: Declaration of Competing Interest None.

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., Competing Interests: Declaration of Competing Interest Dr. Sultan receives institutional research support from Abbott, Artivion, Boston Scientific, Edwards, Medtronic, Terumo Aortic. Dr. Chu is proctor and consultant for Sanamedi, Inc. The remaining authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Sternal closure after median sternotomy traditionally uses a stainless steel wire cerclage. Sternal wires are placed through or around the sternum, and the wire ends are twisted together to bring the sternum back together. Complications of this technique include sternal instability, dehiscence, non-union, and increased pain. Compared to traditional wire cerclage, the Figure 8 FlatWire Sternal Closure System has been demonstrated to be stronger and significantly reduce sternal cut-through and postoperative pain. There was no significant difference in hospital length of stay or mean hospitalization cost. Operative time was slightly longer in the FlatWire group, but this difference has been attributed to the learning curve of mastering the FlatWire technique. This article and supplemental video will demonstrate the technique of FlatWire Sternal Closure System. Briefly, the FlatWire is placed around the sternum, and the FlatWire end is fed through the security box. Once all of the wires are placed, the Figure 8 tensioning device is used to tighten each wire through the security box to the appropriate tensile force. Next, the FlatWires are rotated 90 degrees to hold the sternal position temporarily. Once sternal approximation is achieved, each FlatWire is twisted 120 degrees, and any excess length of the FlatWire is clipped., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-110/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

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.

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., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The epidemiology of mitral stenosis (MS) continues to evolve in the United States. Although the incidence of rheumatic MS has decreased in high-income countries, there is a paucity of data surrounding trends in percutaneous balloon mitral valvuloplasty (PBMV), the current first-line management strategy. This study aimed to identify contemporary trends in PBMV in the United States. Hospitalizations for adults (≥18 years) with MS who underwent PBMV were identified from the National Inpatient Sample from 2008 to 2018. Baseline co-morbidities and outcomes over the study period were determined using Poisson regression. There were 3,980 weighted PBMV cases, 70% of which were women. PBMV hospitalizations decreased from 603 in 2008 to 210 in 2018 (p &lt;0.001). From 2008 to 2018, the age at hospitalization was unchanged in both female and male patients. In contrast, the Charlson Co-morbidity Index increased in both. Baseline heart failure (39% to 64%), hypertension (38% to 43%), and diabetes mellitus (17% to 26%) all substantially increased over the study period. In-hospital mortality occurred in 2% of female and 5% of male patients and was unchanged from 2008 to 2018. Vascular complications (12%) and acute kidney injury (10%) were the most frequent postprocedural complications during the 11-year study period. A composite of mortality or any postprocedural complication did not vary by gender (odds ratio 1.23, 95% confidence interval 0.88 to 1.72). In conclusion, the use of PBMV significantly decreased from 2008 to 2018, and patients with MS who underwent PBMV over this period had an increased burden of co-morbidities, elevated postprocedural complication rate, and no change in in-hospital mortality., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Our case is a 73-year-old male patient with persistent ventricular tachycardia leading to recent syncopal episodes despite ventricular tachycardia ablation and multiple stellate ganglion blocks, frequent hospital admissions, and acute on chronic congestive heart failure requiring an intraaortic balloon pump. The decision was made to proceed with left ventricular assist device placement and bilateral sympathectomies simultaneously. After performing the sternotomy and widely opening bilateral pleural spaces, the lower third of the stellate ganglia to the level of T4 was removed using a combination of the thoracoscope with the sternotomy incision. The use of thoracoscopy greatly assisted with visualization during the sympathectomy., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Coronary heart disease (CHD) has been the number one killer in the United States for decades and causes millions of deaths each year. Clinical treatment of heart ischemic injury relieves symptoms in the acute stage of CHD; however, patients with an infarcted heart muscle can develop heart failure (HF) due to chronic maladaptive remodeling. Regenerative therapy has been studied as a potential treatment option for myocardial infarction (MI) and HF. Cardiac patches have been designed and tested to increase therapeutic retention and integration. However, the delivery usually requires invasive surgical techniques, including open-chest surgeries and heart manipulation. Those procedures may cause chronic adhesions between the heart anterior wall and the chest wall. This study created and tested an injectable ExoGel by embedding mesenchymal stem cell (MSC) -derived exosomes into a hyaluronic acid (HA) hydrogel. ExoGel was injected into the pericardial cavity of rats with transverse aortic constriction (TAC) induced heart failure. ExoGel therapy reduced LV chamber size and preserved wall thickness. The feasibility and safety of ExoGel injection were further confirmed in a pig model., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: To determine the safety and efficacy of the conveyor cardiovascular system (CCS) to facilitate the delivery of large profile transcatheter valve devices., Background: Transcatheter valve devices rely on force provided by the operator to be delivered to their intended position. This delivery may be challenging in a variety of anatomic scenarios. The ability to provide steering from the tip of the device by forming an arterial venous loop may help overcome these challenges., Methods: Between May, 2019 and October, 2020, five patients were recruited for delivery of transcatheter valve devices with the CCS. These patients were deemed by the operators to have challenging anatomy which could make conventional valve delivery difficult or impossible. These patients were recruited as part of an FDA approved early feasibility study or through an institutional review board approved compassionate use protocol., Results: Three patients underwent transcatheter mitral valve replacement with a SAPIEN-3 valve. One patient each underwent transcatheter aortic valve (TAVR) implantation with a SAPIEN 3 and 1 patient underwent TAVR implantation with a Lotus valve. All patients underwent successful implantation of the valve and removal of the CCS and valve delivery systems. There was no more than trivial mitral regurgitation post procedure in any patient and there was no more than trivial paravavular leak. There were no major in-hospital complications., Conclusions: The CCS facilitates the delivery of large profile transcatheter valve devices in challenging anatomic scenarios. Further studies are needed with additional valve technologies., (© 2021 Wiley Periodicals LLC.)

Objective: Evaluate transcatheter mitral valve replacement (TMVR) valve-in-valve (VIV) outcomes in three different mitral bioprostheses (of comparable measured internal diameters) under stable hemodynamic and surgical conditions by bench, echocardiographic, computerized tomography (CT), and autopsy comparisons pre- and post-valve implantation in a porcine model under matched controlled conditions., Background: Impact of surgical bioprosthesis design on TMVR VIV procedures is unknown., Methods: Fifteen similar-sized Yorkshire pigs underwent pre-procedural CT screening. Twelve had consistent anatomic features and underwent implantation of mitral bioprostheses. Four valves from each of three manufacturers were implanted in randomized fashion: 27-mm Epic, 27-mm Mosaic, and 25-mm Mitris, followed by TMVR VIV with 26 Edwards Sapien3. Post-VIV, suprasternal TEE studies were performed to assess hemodynamic function, followed by a gated contrast CT. After euthanasia, animals underwent necropsy for anatomic evaluation., Results: All 12 animals had successful VIV implantation with no study deaths. The post vivMitris (3.77 ± 0.36)/(2.2 ± 0.25 mmHg) had the lowest peak/mean trans-mitral gradient and the vivEpic the highest (15.5 ± 2.55)/(7.09 ± 1.13 mmHg). All THVs (transcatheter heart valves) had greatest deformation within the center of the THV frame; with the smallest waist opening area in the vivEpic (329 ± 35.8 mm 2 ) and greatest in the vivMitris (414 ± 33.12 mm 2 ). Bioprosthetic frames without obvious radiopaque markers resulted in the most ventricular implantation of the THV's anteroseptal frame (Epic: -4.52 ± 0.76 mm), versus the most radiopaque bioprosthesis (Mitris: -1.18 ± 2.95 mm), and higher peak LVOT gradients (Epic: 4.82 ± 1.61 mmHg; Mitris: 2.91 ± 1.47 mmHg)., Conclusions: The current study demonstrates marked variations in hemodynamics, THV opening area, and anatomic dimensions among measured similarly sized mitral bioprostheses. These data suggest a critical need for understanding the potential impact of variations in bioprosthesis design on TMVR VIV clinical outcomes., (© 2021 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Background/aim: To evaluate three mitral bioprostheses (of comparable measured internal diameters) under controlled, stable, hemodynamic and surgical conditions by bench, echocardiographic, computerized tomography and autopsy comparisons pre- and postvalve implantation., Methods: Fifteen similar-sized Yorkshire pigs underwent preprocedural computerized tomography anatomic screening. Of these, 12 had consistent anatomic features and underwent implantation of a mitral bioprosthesis via thoracotomy on cardiopulmonary bypass (CPB). Four valves from each of three manufacturers were implanted in randomized fashion: 27-mm Epic, 27-mm Mosaic, and 25-mm Mitris bioprostheses. After CPB, epicardial echocardiographic studies were performed to assess hemodynamic function and define any paravalvular leaks, followed by postoperative gated contrast computerized tomography. After euthanasia, animals underwent necropsy for anatomic evaluation., Results: All 12 animals had successful valve implantation with no study deaths. Postoperative echocardiographic trans-valve gradients varied among bioprosthesis manufacturers. The 25-mm Mitris (5.1 ± 2.7)/(2.6 ± 1.3 torr) had the lowest peak/mean gradient and the 27-mm Epic bioprosthesis had the highest (9.2 ± 3.7)/(4.6 ± 1.9 torr). Surgical valve opening area (SOA) varied with the 25-mm Mitris having the largest SOA (2.4 ± 0.15 cm 2 ) followed by the 27-mm Mosaic (2.04 ± 0.23 cm 2 ) and the 27-mm Epic (1.8 ± 0.27 cm 2 ) valve. Bench device orthogonal internal diameter measurements did not match manufacturer device size labeling: 25-mm Mitris (23 × 23 mm), 27-mm Mosaic (23 × 22 mm), 27-mm Epic (21 × 21 mm)., Conclusions: Current advertisement/packaging of commercial surgical mitral valves is not uniform. This study demonstrates marked variations in hemodynamics, valve opening area and anatomic dimensions between similar sized mitral bioprostheses. These data suggest a critical need for standardization and close scientific evaluation of surgical mitral bioprostheses to ensure optimal clinical outcomes., (© 2021 The Authors. Journal of Cardiac Surgery published by Wiley Periodicals LLC.)

Objective: Bioprosthetic heart valves (BHVs) are commonly used in surgical and percutaneous valve replacement. The durability of percutaneous valve replacement is unknown, but surgical valves have been shown to require reintervention after 10 to 15 years. Further, smaller-diameter surgical BHVs generally experience higher rates of prosthesis-patient mismatch, which leads to higher rates of failure. Bioprosthetic aortic valves can flutter in systole, and fluttering is associated with fatigue and failure in flexible structures. The determinants of flutter in BHVs have not been well characterized, despite their potential to influence durability., Methods: We use an experimental pulse duplicator and a computational fluid-structure interaction model of this system to study the role of device geometry on BHV dynamics. The experimental system mimics physiological conditions, and the computational model enables precise control of leaflet biomechanics and flow conditions to isolate the effects of variations in BHV geometry on leaflet dynamics., Results: Both experimental and computational models demonstrate that smaller-diameter BHVs yield markedly higher leaflet fluttering frequencies across a range of conditions. The computational model also predicts that fluttering frequency is directly related to leaflet thickness. A scaling model is introduced that rationalizes these findings., Conclusions: We systematically characterize the influence of BHV diameter and leaflet thickness on fluttering dynamics. Although this study does not determine how flutter influences device durability, increased flutter in smaller-diameter BHVs may explain how prosthesis-patient mismatch could induce BHV leaflet fatigue and failure. Ultimately, understanding the effects of device geometry on leaflet kinematics may lead to more durable valve replacements., Competing Interests: Conflict of Interest Statement Dr Vavalle serves as a consultant for Edwards Lifesciences. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

Revascularization of the coronary arteries, via open sternotomy and on cardiopulmonary bypass, remains the most common cardiac surgical procedure in the United States. Patients, and cardiologists, seek an alternative to dividing the sternum while reaping the advantages of left internal mammary artery (LIMA) revascularization of the diseased left anterior descending (LAD) coronary artery. We describe a strictly transxiphoid mammary artery liberation with anastomosis to the anterior descending (TRAX CABG) without sternal division. Of the 26 patients who underwent attempted TRAX CABG, 18 had nonsternotomy LIMA-to-LAD revascularization with completion angiogram to document bypass patency. TRAX CABG offers surgeons a minimally invasive alternative to trans-sternal LIMA-to-LAD in select patients. Conversion to traditional sternotomy has limited unanticipated morbidity and completion angiogram confirms procedural success.

Cardiac patches are an effective way to deliver therapeutics to the heart. However, such procedures are normally invasive and difficult to perform. Here, we develop and test a method to utilize the pericardial cavity as a natural "mold" for in situ cardiac patch formation after intrapericardial injection of therapeutics in biocompatible hydrogels. In rodent models of myocardial infarction, we demonstrate that intrapericardial injection is an effective and safe method to deliver hydrogels containing induced pluripotent stem cells-derived cardiac progenitor cells or mesenchymal stem cells-derived exosomes. After injection, the hydrogels form a cardiac patch-like structure in the pericardial cavity, mitigating immune response and increasing the cardiac retention of the therapeutics. With robust cardiovascular repair and stimulation of epicardium-derived cells, the delivered therapeutics mitigate cardiac remodeling and improve cardiac functions post myocardial infarction. Furthermore, we demonstrate the feasibility of minimally-invasive intrapericardial injection in a clinically-relevant porcine model. Collectively, our study establishes intrapericardial injection as a safe and effective method to deliver therapeutic-bearing hydrogels to the heart for cardiac repair.

We have modified the HeartMate 3 (Abbott, Abbott Park, IL) implantation technique to better suit our patient population. This modification optimizes the placement of the HeartMate 3 sewing cuff and allows passage of the suture transmurally from endocardium to epicardium in a "cut then sew" technique. We believe this affords a superior seal and protection from tearing friable myocardium., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Idiopathic pulmonary fibrosis (IPF) is a fatal and incurable form of interstitial lung disease in which persistent injury results in scar tissue formation. As fibrosis thickens, the lung tissue loses the ability to facilitate gas exchange and provide cells with needed oxygen. Currently, IPF has few treatment options and no effective therapies, aside from lung transplant. Here we present a series of studies utilizing lung spheroid cell-secretome (LSC-Sec) and exosomes (LSC-Exo) by inhalation to treat different models of lung injury and fibrosis. Analysis reveals that LSC-Sec and LSC-Exo treatments could attenuate and resolve bleomycin- and silica-induced fibrosis by reestablishing normal alveolar structure and decreasing both collagen accumulation and myofibroblast proliferation. Additionally, LSC-Sec and LSC-Exo exhibit superior therapeutic benefits than their counterparts derived from mesenchymal stem cells in some measures. We showed that an inhalation treatment of secretome and exosome exhibited therapeutic potential for lung regeneration in two experimental models of pulmonary fibrosis.

Background: There is a higher prevalence of aortic stenosis (AS) in patients with advanced chronic kidney disease (CKD) and European ancestry. However, studies comparing AS progression in white and black patients in an advanced CKD population do not exist., Methods: Advanced CKD (stage IV-V) patients who were referred to the UNC Cardiorenal Clinic for pre-operative kidney transplant evaluation, and diagnosed with either AS (mild, moderate, or severe) or a left ventricular outflow tract velocity ≥2 m/s at any point between 2006-2016 were eligible for inclusion. Serial transthoracic echocardiograms over the 10-year period determined AS progression. All echocardiograms acquired after renal transplantation or aortic valve replacement were excluded. The rates of change of three indices of AS severity [mean gradient, aortic valve area (AVA), and aortic valve velocity] were compared between white and black patients. Mixed effects linear models with repeated measures were used to estimate the overall and race-stratified yearly rate of progression for each index, adjusted for age, sex, smoking status, dialysis, and baseline cholesterol., Results: Of 1,283 patients, 140 (34% white, 66% black) developed or had baseline AS. Initially, 81% had no AS, 13% had mild, and 6% had moderate. White patients were more likely to be male and less likely to be on hemodialysis compared to black patients. No differences in AS severity (P=0.55) or age (60 vs . 58 years, P=0.34) were seen at baseline. In white vs . black patients, mean gradient increased at 1.90 (95% CI: 0.79, 3.01) mmHg/year vs . 1.46 (95% CI, 0.79, 2.14) mmHg/year, P=0.20, AVA decreased at -0.10 (95% CI: -0.15, -0.05) m 2 /year vs . -0.08 (95% CI: -0.11, -0.05) m 2 /year, P=0.13, and transvalvular velocity increased at 0.11 (95% CI: 0.04, 0.18) m/s/year vs . 0.07 (95% CI: 0.03, 0.11) m/s/year, P=0.09., Conclusions: Compared to black patients, white patients in an advanced CKD cohort may have exhibited more rapid progression of AS. Ours is the first study to analyze racial differences in such a population. A study with a larger sample size is needed to confirm our findings., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Several operations in cardiothoracic surgery have been accurately modeled with tissue-based simulations. These have been shown to be beneficial in the training of residents. Cardiac transplantation has not been simulated. We describe a high-fidelity, tissue-based simulation that can be used to teach trainees to perform a cardiac transplant. We modified the existing Ramphal Cardiac Surgery Simulator to accommodate cardiac transplantation. An attending cardiac surgeon successfully performed the simulated transplant, demonstrating each of the component tasks of the operation. We believe our simulation will enhance the training of cardiothoracic surgery residents., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Cardiovascular disease is the leading cause of mortality worldwide. While reperfusion therapy is vital for patient survival post-heart attack, it also causes further tissue injury, known as myocardial ischemia/reperfusion (I/R) injury in clinical practice. Exploring ways to attenuate I/R injury is of clinical interest for improving post-ischemic recovery. A platelet-inspired nanocell (PINC) that incorporates both prostaglandin E2 (PGE 2 )-modified platelet membrane and cardiac stromal cell-secreted factors to target the heart after I/R injury is introduced. By taking advantage of the natural infarct-homing ability of platelet membrane and the overexpression of PGE 2 receptors (EPs) in the pathological cardiac microenvironment after I/R injury, the PINCs can achieve targeted delivery of therapeutic payload to the injured heart. Furthermore, a synergistic treatment efficacy can be achieved by PINC, which combines the paracrine mechanism of cell therapy with the PGE 2 /EP receptor signaling that is involved in the repair and regeneration of multiple tissues. In a mouse model of myocardial I/R injury, intravenous injection of PINCs results in augmented cardiac function and mitigated heart remodeling, which is accompanied by the increase in cycling cardiomyocytes, activation of endogenous stem/progenitor cells, and promotion of angiogenesis. This approach represents a promising therapeutic delivery platform for treating I/R injury., Competing Interests: Conflict of Interest The authors declare no conflict of interest.

Rationale: Cardiac lymphangiogenesis contributes to the reparative process post-myocardial infarction, but the factors and mechanisms regulating it are not well understood., Objective: To determine if epicardial-secreted factor AM (adrenomedullin; Adm=gene) improves cardiac lymphangiogenesis post-myocardial infarction via lateralization of Cx43 (connexin 43) in cardiac lymphatic vasculature., Methods and Results: Firstly, we identified sex-dependent differences in cardiac lymphatic numbers in uninjured mice using light-sheet microscopy. Using a mouse model of Adm hi/hi ( Adm overexpression) and permanent left anterior descending ligation to induce myocardial infarction, we investigated cardiac lymphatic structure, growth, and function in injured murine hearts. Overexpression of Adm increased lymphangiogenesis and cardiac function post-myocardial infarction while suppressing cardiac edema and correlated with changes in Cx43 localization. Lymphatic function in response to AM treatment was attenuated in mice with a lymphatic-specific Cx43 deletion. In vitro experiments in cultured human lymphatic endothelial cells identified a novel mechanism to improve gap junction coupling by pharmaceutically targeting Cx43 with verapamil. Finally, we show that connexin protein expression in cardiac lymphatics is conserved between mouse and human., Conclusions: AM is an endogenous, epicardial-derived factor that drives reparative cardiac lymphangiogenesis and function via Cx43, and this represents a new therapeutic pathway for improving myocardial edema after injury.

We engineered a microneedle patch integrated with cardiac stromal cells (MN-CSCs) for therapeutic heart regeneration after acute myocardial infarction (MI). To perform cell-based heart regeneration, cells are currently delivered to the heart via direct muscle injection, intravascular infusion, or transplantation of epicardial patches. The first two approaches suffer from poor cell retention, while epicardial patches integrate slowly with host myocardium. Here, we used polymeric MNs to create "channels" between host myocardium and therapeutic CSCs. These channels allow regenerative factors secreted by CSCs to be released into the injured myocardium to promote heart repair. In the rat MI model study, the application of the MN-CSC patch effectively augmented cardiac functions and enhanced angiomyogenesis. In the porcine MI model study, MN-CSC patch application was nontoxic and resulted in cardiac function protection. The MN system represents an innovative approach delivering therapeutic cells for heart regeneration.

Background: As transcatheter aortic valve replacement (TAVR) extends its reach to lower surgical risk patients, the differences between resource utilization for TAVR and surgical AVR (SAVR) will become increasingly important., Methods and Results: AVR procedures between January 2012 and September 2015 at hospitals performing TAVR were identified using the National Inpatient Sample databases. Adults aged ≥50 years with aortic stenosis who underwent isolated TAVR or SAVR were eligible for inclusion. Standardized morbidity ratio weights were calculated using patient demographics, comorbidities, and hospital characteristics. Weighted linear and generalized logistic regression models were used to estimate the effect of undergoing TAVR, compared with undergoing SAVR, on length of stay (LOS) and discharge disposition. In TAVR-performing hospitals, 7266 (40%) patients underwent TAVR (6107 endovascular approach and 1159 transapical approach), while 10 833 (60%) underwent isolated SAVR. Patients undergoing TAVR were older, more likely to be female, and had more comorbidities. From 2012 to 2015, average LOS declined for both TAVR (6.3 days to 4.6 days; P<0.0001) and SAVR (7.5 days to 6.8 days; P<0.0001), with greater reduction in the TAVR group ( P<0.0001). An increase in home/home health discharge was noted with TAVR (67.7%-77.4%; P<0.0001) but not with SAVR (76.8%-79.5%; P=0.25). After standardizing, patients undergoing TAVR had significantly shorter LOS (change in estimate, -2.93, 95% CI, -3.26 to -2.60) and lower incidence of transfer to skilled nursing facility (odds ratio, 0.45; 95% CI, 0.40-0.51) but no difference in in-hospital mortality (odds ratio, 0.85; 95% CI, 0.61-1.20) compared with if they had undergone SAVR. As compared with SAVR, patients who had TAVR performed via an endovascular approach had shorter LOS and lower rates of skilled nursing facility transfer, whereas in the transapical cohort, LOS, and skilled nursing facility transfer were similar to SAVR., Conclusions: As compared with if they undergo SAVR, patients undergoing TAVR (by a nontransapical approach) had a shorter LOS and higher likelihood of home discharge, as opposed to skilled nursing facility. From 2012 to 2015, there was a greater trend towards a reduction of LOS and more home discharges among TAVR, as opposed to SAVR. These data have important implications in the era of constrained resources with a growing emphasis on reducing health care costs.

Cardiac stromal cells (CSCs) can be derived from explant cultures, and a subgroup of these cells is viewed as cardiac mesenchymal stem cells due to their expression of CD90. Here, we sought to determine the therapeutic potential of CD90-positive and CD90-negative CSCs in a rat model of chronic myocardial infarction. We obtain CD90-positive and CD90-negative fractions of CSCs from rat myocardial tissue explant cultures by magnetically activated cell sorting. In vitro, CD90-negative CSCs outperform CD90-positive CSCs in tube formation and cardiomyocyte functional assays. In rats with a 30-day infarct, injection of CD90-negative CSCs augments cardiac function in the infarct in a way superior to that from CD90-positive CSCs and unsorted CSCs. Histological analysis revealed that CD90-negative CSCs increase vascularization in the infarct. Our results suggest that CD90-negative CSCs could be a development candidate as a new cell therapy product for chronic myocardial infarction., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

BioGlue is a surgical adhesive widely used to help reinforce complex cardiac and vascular repairs. Since its introduction, several case reports have emerged revealing complications that all providers should be mindful of whenever the product is used. This report considers a unique situation where BioGlue was used after double cardiac valve repair that resulted in adhesion of the new mechanical aortic valve leaflets and was difficult to visualize with transesophageal echocardiography.

Background: In the recently concluded PARTNER 2 trial, TF-TAVR cohort was shown to have lower risks of death or disabling strokes as compared to SAVR, whereas the outcomes with transthoracic TAVR were comparable with SAVR., Methods: We searched PubMed, EMBASE, Web of Science, and Google Scholar for all comparison studies between TAVR and SAVR and mortality as an outcome, irrespective of surgical risk. Randomized controlled trials and propensity-score-matched cohort studies that used a transfemoral approach exclusively or stratified results by route of access and reported data for TF-TAVR patients were eligible for inclusion. Outcomes of interest included 30-day and 1-year mortality, and 30-day complications. If significant heterogeneity was found in the random effects meta-analyses, a sensitivity analysis which individually removed each study was conducted., Results: Seven studies reported results on TF-TAVR. Compared with SAVR, TF-TAVR had comparable 30-day mortality (RR 0.79, 95% CI 0.58, 1.06), 1-year mortality (RR 0.91, 95% CI 0.78, 1.08) and 30-day risk of bleeding (RR 0.70, 95% CI 0.31, 1.57). However, TF-TAVR was associated with lower 30-day risks of atrial fibrillation (RR 0.28, 95% CI 0.17, 0.45), acute kidney injury (RR 0.38, 95% CI 0.20, 0.71), and myocardial infarction (RR 0.41, 95% CI 0.23, 0.75) at a cost of higher incidences of vascular complications (RR 6.10, 95% CI 2.92, 12.73) and pacemaker implantations (RR 3.29, 95% CI 1.41, 7.65)., Conclusions: TF-TAVR is associated with lower 30-day risks of myocardial infarction compared to SAVR. Further studies are required to investigate the role of myocardial injury on overall TF-TAVR outcomes., (© 2017 Wiley Periodicals, Inc.)

Rationale: Cardiac stem cell-derived exosomes have been demonstrated to promote cardiac regeneration following myocardial infarction in preclinical studies. Recent studies have used intramyocardial injection in order to concentrate exosomes in the infarct. Though effective in a research setting, this method is not clinically appealing due to its invasive nature. We propose the use of a targeting peptide, cardiac homing peptide (CHP), to target intravenously-infused exosomes to the infarcted heart. Methods: Exosomes were conjugated with CHP through a DOPE-NHS linker. Ex vivo targeting was analyzed by incubating organ sections with the CHP exosomes and analyzing with fluorescence microscopy. In vitro assays were performed on neonatal rat cardiomyocytes and H9C2 cells. For the animal study, we utilized an ischemia/reperfusion rat model. Animals were treated with either saline, scramble peptide exosomes, or CHP exosomes 24 h after surgery. Echocardiography was performed 4 h after surgery and 21 d after surgery. At 21 d, animals were sacrificed, and organs were collected for analysis. Results: By conjugating the exosomes with CHP, we demonstrate increased retention of the exosomes within heart sections ex vivo and in vitro with neonatal rat cardiomyocytes. In vitro studies showed improved viability, reduced apoptosis and increased exosome uptake when using CHP-XOs. Using an animal model of ischemia/reperfusion injury, we measured the heart function, infarct size, cellular proliferation, and angiogenesis, with improved outcomes with the CHP exosomes. Conclusions: Our results demonstrate a novel method for increasing delivery of for treatment of myocardial infarction. By targeting exosomes to the infarcted heart, there was a significant improvement in outcomes with reduced fibrosis and scar size, and increased cellular proliferation and angiogenesis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Stem cell transplantation, as used clinically, suffers from low retention and engraftment of the transplanted cells. Inspired by the ability of platelets to recruit stem cells to sites of injury on blood vessels, we hypothesized that platelets might enhance the vascular delivery of cardiac stem cells (CSCs) to sites of myocardial infarction injury. Here, we show that CSCs with platelet nanovesicles fused onto their surface membranes express platelet surface markers that are associated with platelet adhesion to injury sites. We also find that the modified CSCs selectively bind collagen-coated surfaces and endothelium-denuded rat aortas, and that in rat and porcine models of acute myocardial infarction the modified CSCs increase retention in the heart and reduce infarct size. Platelet-nanovesicle-fused CSCs thus possess the natural targeting and repairing ability of their parental cell types. This stem cell manipulation approach is fast, straightforward and safe, does not require genetic alteration of the cells, and should be generalizable to multiple cell types., Competing Interests: Competing interests The authors declare no competing interests.

Objective: Recently, the PARTNER 2A trial reported results of transcatheter aortic valve replacement versus surgical aortic valve replacement in 2032 intermediate-risk patients at 2 years. Two hundred thirty-six patients (24%) required an access route other than transfemoral. Compared with transfemoral and surgical aortic valve replacement, nontransfemoral transcatheter aortic valve replacement was associated with a numerically higher rate of death and disabling stroke at 30 days. This underscores the need for a better alternative surgical approach for patients with marginal femoral access. We reviewed our multicenter experience with minimally invasive suprasternal transcatheter aortic valve replacement., Methods: Consecutive patients with symptomatic severe aortic stenosis at high or intermediate risk for surgical aortic valve replacement underwent suprasternal transcatheter aortic valve replacement. A commercially available transcatheter heart valve was deployed under fluoroscopic guidance through the innominate artery or ascending aorta. Using a 3-cm skin incision just above the sternal notch, the Aegis Transit System (Aegis Surgical Ltd, Galway, Ireland) provided illuminated access to the mediastinum without bone disruption. Through a purse-string suture placed in the innominate artery or ascending aorta, transcatheter aortic valve replacement proceeded similarly to the direct aortic approach., Results: Thirty patients at six medical centers successfully underwent suprasternal transcatheter aortic valve replacement. Implanted valves included 2 CoreValve and 12 Evolut-R (Medtronic, Inc, Minneapolis, MN USA), as well as 10 SAPIEN 3 and 6 SAPIEN XT (Edwards Lifesciences, Corp, Irvine, CA USA) with sizes ranging from 23 to 31 mm. Median procedure time was 90 minutes and median hospital stay was 4 days. Postoperatively, new permanent pacemaker (n = 3) was the most common Vascular Academic Research Consortium 2 complication., Conclusions: These data demonstrate the early clinical feasibility of suprasternal transcatheter aortic valve replacement. Key advantages of this approach include direct access to the innominate artery and ascending aorta, precise sheath control, and confident arterial closure. Additional experience is warranted to confirm these favorable results.

Stem cell transplantation is currently implemented clinically but is limited by low retention and engraftment of transplanted cells and the adverse effects of inflammation and immunoreaction when allogeneic or xenogeneic cells are used. Here, we demonstrate the safety and efficacy of encapsulating human cardiac stem cells (hCSCs) in thermosensitive poly(N-isopropylacrylamine-co-acrylic acid) or P(NIPAM-AA) nanogel in mouse and pig models of myocardial infarction (MI). Unlike xenogeneic hCSCs injected in saline, injection of nanogel-encapsulated hCSCs does not elicit systemic inflammation or local T cell infiltrations in immunocompetent mice. In mice and pigs with acute MI, injection of encapsulated hCSCs preserves cardiac function and reduces scar sizes, whereas injection of hCSCs in saline has an adverse effect on heart healing. In conclusion, thermosensitive nanogels can be used as a stem cell carrier: the porous and convoluted inner structure allows nutrient, oxygen, and secretion diffusion but can prevent the stem cells from being attacked by immune cells.

Purpose: Suprasternal transcatheter aortic valve replacement offers patients, with unsuitable femoral artery anatomy, an alternative to transapical, direct aortic, and subclavian approaches., Description: The Transit System (Aegis Surgical, Galway, Ireland) enables transcatheter aortic valve replacement directly into the ascending aorta or innominate artery through a small, suprasternal incision. The valve introducer sheath is inserted through a standard pursestring suture, which facilitates secure arterial closure. The proximity to the aortic valve promotes precise control., Evaluation: Proper patient selection and preoperative imaging is essential. A heart team working collaboratively in a hybrid operating room ensures procedural success. Using this approach, four different manufacturer's transcatheter valves have been used successfully., Conclusions: Suprasternal transcatheter aortic valve replacement is a safe and effective addition to the surgeon's armamentarium., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Each year, approximately 300,000 heart valve repair or replacement procedures are performed worldwide, including approximately 70,000 aortic valve replacement surgeries in the United States alone. Computational platforms for simulating cardiovascular devices such as prosthetic heart valves promise to improve device design and assist in treatment planning, including patient-specific device selection. This paper describes progress in constructing anatomically and physiologically realistic immersed boundary (IB) models of the dynamics of the aortic root and ascending aorta. This work builds on earlier IB models of fluid-structure interaction (FSI) in the aortic root, which previously achieved realistic hemodynamics over multiple cardiac cycles, but which also were limited to simplified aortic geometries and idealized descriptions of the biomechanics of the aortic valve cusps. By contrast, the model described herein uses an anatomical geometry reconstructed from patient-specific computed tomography angiography (CTA) data, and employs a description of the elasticity of the aortic valve leaflets based on a fiber-reinforced constitutive model fit to experimental tensile test data. The resulting model generates physiological pressures in both systole and diastole, and yields realistic cardiac output and stroke volume at physiological Reynolds numbers. Contact between the valve leaflets during diastole is handled automatically by the IB method, yielding a fully competent valve model that supports a physiological diastolic pressure load without regurgitation. Numerical tests show that the model is able to resolve the leaflet biomechanics in diastole and early systole at practical grid spacings. The model is also used to examine differences in the mechanics and fluid dynamics yielded by fresh valve leaflets and glutaraldehyde-fixed leaflets similar to those used in bioprosthetic heart valves. Although there are large differences in the leaflet deformations during diastole, the differences in the open configurations of the valve models are relatively small, and nearly identical hemodynamics are obtained in all cases considered., (Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.)

Background: The results from the PARTNER 2 trial showed the feasibility of transcatheter aortic valve replacement (TAVR) in intermediate surgical risk patients. Although low risk clinical trials will take time to conclude, some data has emerged comparing TAVR with surgical aortic valve replacement (SAVR) in lower risk patients., Methods: A Medline search was conducted using standard methodology to search for studies reporting results comparing TAVR and SAVR. Studies were included if the overall mean Society of Thoracic Surgeons Score was less than 4% (or equivalent Euroscore). A meta-analysis comparing the 30-day risk of clinical outcomes between TAVR and SAVR in the lower surgical risk population was conducted., Results: A total of four studies, including one clinical trial and three propensity-matched cohort studies met the inclusion criteria. Compared to SAVR, TAVR had a lower risk of 30-day mortality (RR 0.67, 95% CI 0.41, 1.10), stroke (RR 0.60, 95% CI 0.30, 1.22), bleeding complications (RR 0.51, 95% CI 0.40, 0.67) and acute kidney injury (RR 0.66, 95% CI 0.47, 0.94). However, a higher risk of vascular complications (RR 11.72, 95% CI 3.75, 36.64), moderate or severe paravalvular leak (RR 5.04, 95% CI 3.01, 8.43), and permanent pacemaker implantations (RR 4.62, 95% CI 2.63, 8.12) was noted for TAVR., Conclusion: Among lower risk patients, TAVR and SAVR appear to be comparable in short term outcomes. Additional high quality studies among patients classified as low risk are needed to further explore the feasibility of TAVR in all surgical risk patients., (Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

The results of the Placement of AoRtic TraNscathetER Valves (PARTNER) 2 trial established the feasibility of transcatheter aortic valve replacement (TAVR) for intermediate surgical risk patients. The expansion of TAVR into the low-risk patient population will largely depend on its durability outcomes due to the high life expectancy in low-risk patients. Long-term follow-up results from low-risk clinical trials will take several years to be reported. Given this, we performed a systematic review of current long-term data to provide further insights into TAVR durability and long-term patient survival. We searched MEDLINE, Embase, Google Scholar, BIOSIS, and major conference abstracts for TAVR studies with follow-up of at least 4 years. Abstracts were retrieved and independently reviewed for eligibility. Final studies were selected irrespective of the type of TAVR valve, route of vascular access, or surgical risk profile. A total of 12 studies met the inclusion criteria. We reviewed data from these studies with emphasis on long-term survival and echocardiographic findings., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Resident stem and progenitor cells have been identified in the lung over the last decade, but isolation and culture of these cells remains a challenge. Thus, although these lung stem and progenitor cells provide an ideal source for stem-cell based therapy, mesenchymal stem cells (MSCs) remain the most popular cell therapy product for the treatment of lung diseases. Surgical lung biopsies can be the tissue source but such procedures carry a high risk of mortality., Methods: In this study we demonstrate that therapeutic lung cells, termed "lung spheroid cells" (LSCs) can be generated from minimally invasive transbronchial lung biopsies using a three-dimensional culture technique. The cells were then characterized by flow cytometry and immunohistochemistry. Angiogenic potential was tested by in-vitro HUVEC tube formation assay. In-vivo bio- distribution of LSCs was examined in athymic nude mice after intravenous delivery., Results: From one lung biopsy, we are able to derive >50 million LSC cells at Passage 2. These cells were characterized by flow cytometry and immunohistochemistry and were shown to represent a mixture of lung stem cells and supporting cells. When introduced systemically into nude mice, LSCs were retained primarily in the lungs for up to 21 days., Conclusion: Here, for the first time, we demonstrated that direct culture and expansion of human lung progenitor cells from pulmonary tissues, acquired through a minimally invasive biopsy, is possible and straightforward with a three-dimensional culture technique. These cells could be utilized in long-term expansion of lung progenitor cells and as part of the development of cell-based therapies for the treatment of lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).

Layering a regenerative polymer scaffold on the surface of the heart, termed as a cardiac patch, has been proven to be effective in preserving cardiac function after myocardial infarction (MI). However, the placement of such a patch on the heart usually needs open-chest surgery, which is traumatic, therefore prevents the translation of this strategy into the clinic. We sought to device a way to apply a cardiac patch by spray painting in situ polymerizable biomaterials onto the heart with a minimally invasive procedure. To prove the concept, we used platelet fibrin gel as the "paint" material in a mouse model of MI. The use of the spraying system allowed for placement of a uniform cardiac patch on the heart in a mini-invasive manner without the need for sutures or glue. The spray treatment promoted cardiac repair and attenuated cardiac dysfunction after MI.

Stem cell therapy represents a promising strategy in regenerative medicine. However, cells need to be carefully preserved and processed before usage. In addition, cell transplantation carries immunogenicity and/or tumourigenicity risks. Mounting lines of evidence indicate that stem cells exert their beneficial effects mainly through secretion (of regenerative factors) and membrane-based cell-cell interaction with the injured cells. Here, we fabricate a synthetic cell-mimicking microparticle (CMMP) that recapitulates stem cell functions in tissue repair. CMMPs carry similar secreted proteins and membranes as genuine cardiac stem cells do. In a mouse model of myocardial infarction, injection of CMMPs leads to the preservation of viable myocardium and augmentation of cardiac functions similar to cardiac stem cell therapy. CMMPs (derived from human cells) do not stimulate T-cell infiltration in immuno-competent mice. In conclusion, CMMPs act as 'synthetic stem cells' which mimic the paracrine and biointerfacing activities of natural stem cells in therapeutic cardiac regeneration.

Enhanced recovery after surgery (ERAS) protocols have proven effective in a variety of surgical specialties. Published reports on these pathways within cardiac surgery and interventional cardiology are limited. Invasive aortic valve replacement procedures are increasingly being performed by hybrid groups of interventional cardiologists and surgeons through transcatheter aortic valve implantation (TAVI). The TAVI patient population is at a higher surgical risk compared with those undergoing surgical aortic valve replacement since they are older, frailer, and have significant co-morbidities which result in an increased risk of perioperative complications. ERAS protocols have the potential to help these patients undergoing TAVI procedures. In conclusion, we propose a TAVI ERAS protocol with a call-to-action for other centers to implement an ERAS protocol to improve hospital and cardiac outcomes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Transcatheter aortic valve replacement (TAVR) has been approved in patients with high or prohibited surgical risk for surgery for treatment of severe symptomatic aortic stenosis. Prospective studies examining the benefits of TAVR in intermediate risk patients are ongoing. Other smaller studies including lower risk patients have been conducted, but further meta-analysis of these studies is required to draw more broad comparisons., Methods: A Medline search was conducted using standard methodology to search for clinical trials and observational studies including intermediate risk patients. We limited our meta-analysis to studies matching patient populations by propensity scores or randomization and examined clinical outcomes between TAVR and surgical aortic valve replacement (SAVR)., Results: Analysis of the TAVR and SAVR cohorts revealed no significant differences in the outcomes of 30-day [OR (95% CI): 0.85 (0.57, 1.26)] or 1-year mortality [OR (95% CI): 0.96 (0.75, 1.23)]. A trend towards benefit with TAVR was noted in terms of neurological events and myocardial infarction (MI) without statistical significance. A statistically significant decrease in risk of post-procedural acute renal failure in the TAVR group [OR (95% CI): 0.52 (0.27, 0.99)] was observed, but so was a significantly higher rate of pacemaker implantations for the TAVR group [OR (95% CI): 6.51 (3.23, 13.12)]., Conclusions: We conclude that in intermediate risk patients undergoing aortic valve replacement, the risk of mortality, neurological outcomes, and MI do not appear to be significantly different between TAVR and SAVR. However, there appears to be a significant reduction in risk of acute renal failure at the expense of an increased risk of requiring a permanent pacemaker in low and intermediate risk patients undergoing TAVR compared to SAVR.

Unlabelled: Stem cells and biomaterials have been studied for therapeutic cardiac repair. Previous studies have shown the beneficial effects of platelet fibrin gel and cardiac stem cells when cotransplanted into rodent hearts with myocardial infarction (MI). We hypothesized that matrix metalloproteinases (MMPs) play an important role in such protection. Thus, the present study is designed to elucidate the effects of MMP inhibition on the therapeutic benefits of intramyocardial injection of platelet fibrin gel spiked with cardiac stem cells (cell-gel) in a rat model of acute MI. In vitro, broad-spectrum MMP inhibitor GM6001 undermines cell spreading and cardiomyocyte contraction. In a syngeneic rat model of myocardial infarction, MMP inhibition blunted the recruitment of endogenous cardiovascular cells into the injected biomaterials, therefore hindering de novo angiogenesis and cardiomyogenesis. Echocardiography and histology 3 weeks after treatment revealed that metalloproteinase inhibition diminished the functional and structural benefits of cell-gel in treating MI. Reduction of host angiogenesis, cardiomyocyte cycling, and MMP-2 activities was evident in animals treated with GM6001. Our findings suggest that MMPs play a critical role in the therapeutic benefits of platelet fibrin gel spiked with cardiac stem cells for treating MI., Significance: In this study, the effects of matrix metalloproteinase inhibition on the performance of platelet gel spiked with cardiac stem cells (cell-gel) for heart regeneration are explored. The results demonstrate that matrix metalloproteinases are required for cell-gel to exert its benefits in cardiac repair. Inhibition of matrix metalloproteinases reduces cell engraftment, host angiogenesis, and recruitment of endogenous cardiovascular cells in rats with heart attack., (©AlphaMed Press.)