Degeneration of biological heart valve grafts in a rat model of superoxide dismutase-3 deficiency.

While oxidative stress is known as key element in the pathogenesis of atherosclerosis and calcific aortic valve disease, its role in the degeneration of biological cardiovascular grafts has not been clarified yet. Therefore, the present study aimed to examine the impact of oxidative stress on the degeneration of biological cardiovascular allografts in a standardized chronic implantation model realized in rats exhibiting superoxide dismutase 3 deficiency (SOD3(-) ). Rats with SOD3 loss-of-function mutation (n = 24) underwent infrarenal implantation of cryopreserved valved aortic conduits, while SOD3-competent recipients served as controls (n = 28). After a follow-up period of 4 or 12 weeks, comparative analyses addressed degenerative processes, hemodynamics, and evaluation of the oxidative stress model. SOD3(-) rats presented decreased circulating SOD activity (p = .0079). After 12 weeks, 58% of the implant valves in SOD3(-) rats showed regurgitation (vs. 31% in controls, p = .2377). Intima hyperplasia and chondro-osteogenic transformation contributed to progressive graft calcification (p = .0024). At 12 weeks, hydroxyapatite deposition (p = .0198) and the gene expression of runt-related transcription factor-2 (Runx2) (p = .0093) were significantly enhanced in group SOD3(-) . This study provides the first in vivo evidence that impaired systemic antioxidant activity contributes to biological cardiovascular graft degeneration.

Clinical outcomes of hundred large Impella implantations in cardiogenic shock patients based on individual clinical scenarios.

BACKGROUND: Large Impella systems (5.0 or 5.5; i.e., Impella 5+) (Abiomed Inc., Danvers, MA, USA) help achieve better clinical outcomes through relevant left ventricular unloading in acute cardiogenic shock (CS). Here, we report our experience with Impella 5+, while focusing on the clinical outcomes depending on individual case scenarios in patients with acute CS. METHODS: This single-center retrospective observational study included 100 Impella 5+ implantations conducted on patients with acute CS from November 2018 to October 2021. After excluding 10 reimplantation cases, 90 cases were enrolled for further analysis. RESULTS: In-hospital and 30-day mortality rates were 56.7% (n = 51) and 48.9% (n = 44), respectively. In-hospital mortality was lower in patients with acute myocardial infarction (AMI) than in non-AMI patients (p = 0.07). Young age and low lactate levels were the independent predictors of successful transition and survival after permanent mechanical circulatory support/heart transplantation (pMCS/HTX) (age, p = 0.03; lactate level, p = 0.04; survived after pMCS/HTX, n = 11; died on Impella, n = 41). During simultaneous utilization of venoarterial extracorporeal membrane oxygenation therapy and Impella 5+, termed ECMELLA therapy, high dose of noradrenaline was a predictive factor for in-hospital mortality by multivariate analysis (n = 0.02). CONCLUSIONS: Our results suggest that enhanced Impella support might have better clinical outcomes among acute CS patients supported with large Impella, those with AMI than those with no AMI. Young age and low lactate levels were predictors of successful bridging to pMCS/HTX and favorable clinical outcomes thereafter. The clinical outcomes of ECMELLA therapy might depend on noradrenaline dose at the time of Impella 5+ implantation.

Percutaneous Cannulation of Femoral Vessels in Minimally Invasive Cardiac Surgery.

OBJECTIVE: Despite the recent trend of access miniaturization in minimally invasive cardiac surgery (MICS) surgical "cut down (CD)" for femoral cannulation remains the standard at many centers. Percutaneous vascular closure (PVC) devices have recently been introduced for minimizing invasiveness during interventional diagnostic and therapy. This report summarizes the initial experience with this new approach in the setting of MICS, with a special focus on safety and advantages. METHODS: Percutaneous cannulation with a standard protocol including preoperative computer tomography imaging and intraoperative point-of-care ultrasound guidance was performed in 93 consecutive patients from September 2018 until February 2020, while conventional "CD" procedure performed in 218 patients in the previous period. We analyzed patients' characteristics and compared access site complications of PVC group versus conventional "CD" group. RESULTS: As far as operative/postoperative outcome, the duration of intensive care unit stay as well as hospital stay was statistically shorter in PVC compared with CD (CD vs. PVC: 2.74 ± 3.83 vs. 2.16 ± 2.01 days, p < 0.01, 16.7 ± 8.75 vs. 13.0 ± 4.96 days, p < 0.001, respectively). Further, we found no femoral infection or lymphocele in the PVC group, whereas 4 cases of wound complications were observed in the CD group. CONCLUSION: According to our results, percutaneous closure system for femoral vessels in MICS seems to be beneficial with the assist of preoperative computed tomography and intraoperative Doppler guidance.

Coronary artery bypass grafting under sole Impella 5.0 support for patients with severely depressed left ventricular function.

Selection of the ideal surgical procedure for coronary revascularization in patients with severe cardiac dysfunction at times may represent a challenge. In recent years, with the advent of surgical large microaxial pumps, e.g., Impella 5.0 (Abiomed Inc., Boston, USA), specific support and effective unloading of the left ventricle has become available. In the interventional field, good results have been achieved with smaller microaxial pumps in the setting of so-called protected percutaneous coronary intervention. In this study, we would like to share our early experience with surgical coronary revascularization under the sole support of Impella 5.0, omitting the use of heart-lung machine in three cases of severe cardiac dysfunction due to complex ischemic heart disease. Effective circulatory support intraoperatively and postoperatively speaks in favor of this technique in selected patients.

Effect of preoperative erector spinae muscles mass on postoperative outcomes in patients with left ventricular assist devices.

BACKGROUND: Frailty influences the postoperative outcomes in patients undergoing left ventricular assist device (LVAD) implantation. Recently, erector spinae muscle (ESM) mass has been proposed as a parameter to assess frailty accurately. Thus, the purpose of the present study was to evaluate whether preoperative ESM mass is associated with short- and long-term clinical outcomes in patients with LVAD. METHODS: A total of 119 consecutive patients with LVAD were enrolled between January 2010 and October 2017 at a single heart center. The ESM area, ESM index, and Hounsfield units (HU) of the ESM were calculated by computed tomography for preoperative ESM mass evaluation. We then statistically evaluated the in-hospital mortality, major adverse cardiovascular events (MACE), duration of hospital stay, and long-term survival. RESULTS: In a multivariate Cox regression analysis, ESM mass indicated no effect on all clinical outcomes. In addition, the ESM area presented a weak but significant negative linear correlation only with the duration of hospital stay (r = -0.21, p < .05). In contrast, the Model For End-stage Liver Disease (MELD) score and preoperative venous-arterial extracorporeal membrane oxygenation (va-ECMO) were significant predictive factors for in-hospital mortality (MELD score: p < .001, hazard ratio [HR] 1.1; preoperative va-ECMO: p < .01, HR 2.72) and MACE (MELD score: p < .001, HR 1.07; preoperative va-ECMO: p < .005, HR 2.62). CONCLUSION: Preoperative ESM mass might predict the length of hospital stay in patients undergoing LVAD implantation. In contrast, it had no effect on MACE, in-hospital mortality, or long-term survival in this study.

A Role for Peroxisome Proliferator-Activated Receptor Gamma Agonists in Counteracting the Degeneration of Cardiovascular Grafts.

ABSTRACT: Aortic valve replacement for severe stenosis is a standard procedure in cardiovascular medicine. However, the use of biological prostheses has limitations especially in young patients because of calcifying degeneration, resulting in implant failure. Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist, was shown to decrease the degeneration of native aortic valves. In this study, we aim to examine the impact of pioglitazone on inflammation and calcification of aortic valve conduits (AoC) in a rat model. Cryopreserved AoC (n = 40) were infrarenally implanted into Wistar rats treated with pioglitazone (75 mg/kg chow; n = 20, PIO) or untreated (n = 20, controls). After 4 or 12 weeks, AoC were explanted and analyzed by histology, immunohistology, and polymerase chain reaction. Pioglitazone significantly decreased the expression of inflammatory markers and reduced the macrophage-mediated inflammation in PIO compared with controls after 4 (P = 0.03) and 12 weeks (P = 0.012). Chondrogenic transformation was significantly decreased in PIO after 12 weeks (P = 0.001). Calcification of the intima and media was significantly reduced after 12 weeks in PIO versus controls (intima: P = 0.008; media: P = 0.025). Moreover, echocardiography revealed significantly better functional outcome of the AoC in PIO after 12 weeks compared with control. Interestingly, significantly increased intima hyperplasia could be observed in PIO compared with controls after 12 weeks (P = 0.017). Systemic PPAR-gamma activation prevents inflammation as well as intima and media calcification in AoC and seems to inhibit functional impairment of the implanted aortic valve. To further elucidate the therapeutic role of PPAR-gamma regulation for graft durability, translational studies and long-term follow-up data should be striven for.

Impact of Reported Donor Ejection Fraction on Outcome after Heart Transplantation.

OBJECTIVES: The global shortage of donor organs has urged transplanting units to extend donor selection criteria, for example, impaired left ventricular function (LVF), leading to the use of marginal donor hearts. We retrospectively analyzed our patients after orthotopic heart transplantation (oHTX) with a focus on the clinical outcome depending on donor LVF. METHODS: Donor reports, intraoperative, echocardiographic, and clinical follow-up data of patients undergoing oHTX at a single-center between September 2010 and June 2020 were retrospectively analyzed. Recipients were divided into two groups based on donor left ventricular ejection fraction (dLVEF): impaired dLVEF (group I; dLVEF ≤ 50%; n = 23) and normal dLVEF group (group N; dLVEF > 50%; n = 137). RESULTS: There was no difference in 30-day, 90-day, and 1-year survival. However, the duration of in-hospital stay was statistically longer in group I than in group N (N: 40.9 ± 28.3 days vs. I: 55.9 ± 39.4 days, p < 0.05). Furthermore, postoperative infection events were significantly more frequent in group I (p = 0.03), which was also supported by multivariate analysis (p = 0.03; odds ratio: 2.96; confidence interval: 1.12-7.83). Upon correlation analysis, dLVEF and recipient LVEF prove as statistically independent (r = 0.12, p = 0.17). CONCLUSIONS: Impaired dLVEF is associated with prolonged posttransplant recovery and slightly increased morbidity but has no significant impact on survival up to 1 year posttransplant.

Iron deficiency does not impair the outcome after elective coronary artery bypass and aortic valve procedures.

BACKGROUND AND AIM OF THE STUDY: Iron deficiency (ID), a common malnutrition, has been linked to impaired prognosis in patients with congestive heart failure. It remains unclear whether ID also affects the outcome after elective cardiac surgery. METHODS: A total of 378 consecutive patients undergoing either coronary artery bypass grafting (CABG) or surgical aortic valve replacement (SAVR) were prospectively enrolled, and blood samples were taken before surgery for analysis of iron metabolism. Incidence of major adverse cardiovascular and cerebrovascular events (MACCE) was defined as the primary endpoint of the study. RESULTS: ID (ferritin < 100 ng/ml or ferritin = 100-299 ng/ml and transferrin saturation < 20%) was common in cardiac surgery patients (ID, n = 265, 70%) and related to significant decreased preoperative hemoglobin values (ID: 13.6 ± 1.6 g/dl, Non-ID: 14.3 ± 1.5 g/dl, p < 0.01). We did not observe any differences in the postoperative outcome of the two groups. The incidence of MACCE was 4.9% in patients with ID and 8.8% in Non-ID (p = 0.16). In-hospital mortality (ID: 1.9%, Non-ID: 4.4%, p = 0.17) and stroke (ID: 1.1%, Non-ID: 1.8%, p = 0.64) were also not altered by ID. In addition, intensive care unit and hospital stay, perioperative blood transfusions as well as perioperative morbidities, such as acute kidney injury, low cardiac output syndrome, major bleeding complication, and sternal wound infections were comparable in patients with and without ID. CONCLUSIONS: The majority of patients undergoing elective CABG or SAVR suffer from ID; however, we found no significant differences in regard to MACCE and postoperative morbidity between ID and non-ID patients.

Multimodal mechanical circulatory assist for perioperative biventricular failure.

A 61-year-old woman with acute myocardial infarction (MI), cardiogenic shock, and Impella CP support underwent emergency coronary artery bypass grafting. Postoperatively venous-arterial extracorporeal membrane oxygenation (va-ECMO) became necessary, followed by Impella 5.0 insertion on 7th postoperative day (POD), the addition of right ventricular support by TandemHeart due to inadequate flow of Impella system, which then allowed for va-ECMO weaning. Impella und TandemHeart were removed on 14th POD, 31st POD, respectively. Biventricular decompensation following MI was successfully treated by a sequence of different mechanical circulatory support systems allowing an adaptive weaning strategy.

The analysis of left ventricular ejection fraction after minimally invasive surgery for primary mitral valve regurgitation.

BACKGROUND: Although minimally invasive mitral valve surgery (MIMVS) has become the first choice for primary mitral regurgitation (MR) in recent years, clinical evidence in this field is yet limited. The main focus of this study was the analysis of preoperative (Pre), postoperative (Post), and 1-year follow-up (Fu) data in our series of MIMVS to identify factors that have an impact on the left ventricular ejection fraction (LVEF) evolution after MIMVS. METHODS: We reviewed the perioperative and 1-year follow-up data from 436 patients with primary MR (338 isolated MIMVS und 98 MIMVS combined with tricuspid valve repair) to analyze patients' baseline characteristics, the change of LV size, the postoperative evolution of LVEF and its factors, and the clinical outcomes. RESULTS: The overall mean value of ejection fraction (EF) slightly decreased at 1-year follow-up (mean change of LVEF: -2.63 ± 9.00%). A significant correlation was observed for preoperative EF (PreEF) und EF evolution, the higher PreEF the more pronounced decreased EF evolution (in all 436 patients; r = -.54, p < .001, in isolated MIMVS; r = -.54, p < .001, in combined MIMVS; r = -.53, p < .001). Statistically significant differences for negative EF evolution were evident in patients with mild or greater tricuspid valve regurgitation (TR) (in all patients; p < .05, odds ratio [OR] = 1.64, in isolated MIMVS; p < .01, OR = 1.93, respectively). Overall clinical outcome in New York Heart Association classification at 1 year was remarkably improved. CONCLUSIONS: Our results suggest an excellent clinical outcome at 1 year, although mean LVEF slightly declined over time. TR could be a predictor of worsened follow-up LVEF in patients undergoing MIMVS.

PPAR-Gamma Activation May Inhibit the In Vivo Degeneration of Bioprosthetic Aortic and Aortic Valve Grafts under Diabetic Conditions.

BACKGROUND: We aimed to examine the anti-calcification and anti-inflammatory effects of pioglitazone as a PPAR-gamma agonist on bioprosthetic-valve-bearing aortic grafts in a rat model of diabetes mellitus (DM). METHODS: DM was induced in male Wistar rats by high-fat diet with an intraperitoneal streptozotocin (STZ) injection. The experimental group received additional pioglitazone, and controls received normal chow without STZ (n = 20 each group). Cryopreserved aortic donor grafts including the aortic valve were analyzed after 4 weeks and 12 weeks in vivo for analysis of calcific bioprosthetic degeneration. RESULTS: DM led to a significant media proliferation at 4 weeks. The additional administration of pioglitazone significantly increased circulating adiponectin levels and significantly reduced media thickness at 4 and 12 weeks, respectively (p = 0.0002 and p = 0.0107, respectively). Graft media calcification was highly significantly inhibited by pioglitazone after 12 weeks (p = 0.0079). Gene-expression analysis revealed a significant reduction in relevant chondro-osteogenic markers osteopontin and RUNX-2 by pioglitazone at 4 weeks. CONCLUSIONS: Under diabetic conditions, pioglitazone leads to elevated circulating levels of adiponectin and to an inhibition of bioprosthetic graft degeneration, including lower expression of chondro-osteogenic genes, decreased media proliferation, and inhibited graft calcification in a small-animal model of DM.

Risk and Consequences of Postoperative Delirium in Cardiac Surgery.

BACKGROUND: Delirium is a common complication after cardiac surgery that leads to increased costs and worse outcomes. This retrospective study evaluated the potential risk factors and postoperative impact of delirium on cardiac surgery patients. METHODS: One thousand two hundred six patients who underwent open-heart surgery within a single year were included. Uni- and multivariate analyses of a variety of pre, intra-, and postoperative parameters were performed according to differences between the delirium (D) and nondelirium (ND) groups. RESULTS: The incidence of delirium was 11.6% (n = 140). The onset of delirium occurred at 3.35 ± 4.05 postoperative days with a duration of 5.97 ± 5.36 days. There were two important risk factors for postoperative delirium: higher age (D vs. ND, 73.1 ± 9.04 years vs. 69.0 ± 11.1 years, p < 0.001) and longer aortic cross-clamp time (D vs. ND, 69.8 ± 49.9 minutes vs. 61.6 ± 53.8 minutes, p < 0.05). We found that delirious patients developed significantly more frequent postoperative complications, such as myocardial infarction (MI) (D vs. ND, 1.43% [n = 3] vs. 0.28% [n = 2], p = 0.05), cerebrovascular accident (D vs. ND, 10.7% [n = 15] vs. 3.75% [n = 40], p < 0.001), respiratory complications (D vs. ND, 16.4% [n = 23] vs. 5.72% [n = 61], p < 0.001), and infections (D vs. ND, 36.4% [n = 51] vs. 16.0% [n = 170], p < 0.001). The hospital stay was longer in cases of postoperative delirium (D vs. ND, 23.2 ± 13.6 days vs. 17.4 ± 12.8 days, p < 0.001), and fewer patients were discharged home (D vs. ND, 56.0% [n = 65] vs. 66.8% [n = 571], p < 0.001). CONCLUSIONS: Because the propensity for delirium-related complications is high after cardiac surgery, a practical, preventative strategy should be developed for patients with perioperative risk factors, including higher age and a longer cross-clamp time.

Electrophysiological Stimulation of Whole Heart Constructs in an 8-Pole Electrical Field.

Today 2D and 3D electrophysiological stimulation represents a well established concept to enhance myocardial development and maturation in tissue-engineered constructs. However, electrical field stimulation has never been adapted to complex whole heart constructs (WHC). This study demonstrates the impact of three-dimensional electrophysiological stimulation of tissue-engineered WHC in a custom made eight-pole electrical field stimulation system by short model cultivations with neonatal rat cardiomyocytes (CM). Therefore, WHC were generated by repopulation of decellularized rat hearts with neonatal CM and subjected to perfusion based cultivation with or without additional biophysicalstimulation for 96 h. Spontaneous electrophysiological (EP) activity of the processed WHC was analyzed by qualitative evaluation of multielectrode assay (MEA) signal sequences, descriptive comparative spike sorting, and direct contrasting assessment in simple numerical quantities complemented by impulse response tests after phasing out spontaneous EP activity. As strong reduction of voltage signals by the decellularized extracellular matrix (ECM) component of WHC was observed, the active principle was determined and used to estimate the spectrum of source signals to recorded values by calculative elimination. Western blotting of key myocardial markers was employed to substantiate the functional EP evaluation by classical biochemical analysis. We observed stable spontaneous EP activity showing clear R and S, but predominantly rS patterns, for both stimulated WHC and non-stimulated controls. By the impact of stimulation, mean voltage amplitudes and beating frequencies could be significantly increased. The active principle of signal reduction in decellularized ECM could be shown to follow a nonlinear damping function with remarkable accuracy, illustrating that recorded signals of moderate voltage amplitudes can also represent far-field measurements of strong signals that are emitted in distant depths of the ECM while small amplitudes are limited to actually represent also rather weak source-signals. After phasing out spontaneous activity, both stimulated WHC and non-stimulated controls could be excited again to emit immediate impulse responses. The observed beneficial impact of 8-pole field stimulation on functional EP activity could finally be validated on the biochemical level by showing increased ratios for myosin heavy chain, cardiac tropnin T, desmin, and connexin 43 for stimulated WHC by Western blot analysis. In conclusion, we found that although electrophysiological stimulation has been incorporated into the whole heart tissue-engineered concept from the very beginning, this study presents for the first time a concept for the transfer of electrical field stimulation to the whole heart tissue-engineered approach. Furthermore to the best knowledge of the authors, this is the first control-based study showing a comparative investigation of electrophysiological stimulation of whole heart constructs.

[Traumatic injury of the proximal aortic arch after blunt chest trauma;report of a case].

We report a rare case of an proximal aortic arch injury caused by blunt chest trauma. A 48-year-old woman was transferred to our hospital because of traffic accident. Computed tomography (CT) showed a small ulcer-like projection (ULP) at the proximal part of the aortic arch. An elective surgery for aortic repair was performed because of significant enlargement of the ULP in the aortic arch revealed by follow-up CT. The patient's postoperative course was uneventful, and she was discharged on the 14th postoperative day.

Impact of Impella Support on Clinical Outcomes in Patients with Postcardiotomy Cardiogenic Shock.

PURPOSE: This study aimed to elucidate the strategy of an effective Impella support for better clinical outcomes in patients with a postcardiotomy cardiogenic shock (PCCS). METHODS: This single-center retrospective observational study enrolled 31 patients with PCCS undergoing an elective open-heart surgery followed by Impella support between November 2018 and February 2022 for further analysis. RESULTS: The preoperative Euroscore II and left ventricular (LV) ejection fraction were 9.1 ± 10.4 and 35.7% ± 12.6%, respectively. The in-hospital mortality rate was 51.6% (n = 16). In survivors (n = 15), the mean Impella support time was 6.9 ± 3.5 days. Patients were discharged on the postoperative day 24.9 ± 16.4. Regarding LV remodeling, LV end-diastolic diameter was significantly decreased after Impella support (59.2 ± 6.0 mm vs. 54.4 ± 4.7 mm, p = 0.01, preoperative vs. postoperative). In-hospital mortality rates were comparable with small (CP, n = 6) or large (5.0, n = 25) Impella systems (33.3% [n = 2] vs. 56.0% [n = 14], p = 0.39). However, a lower in-hospital mortality rate was observed in the group with early initiation (i.e., intraoperative) of Impella support (n = 14) than that with delayed Impella initiation (i.e., in the postoperative course) (n = 11) (28.6% [n = 4] vs. 90.9% [n = 10], p = 0.004). CONCLUSIONS: Impella support contributes to LV remodeling in PCCS patients. In-hospital mortality was comparable in different Impella sizes and lower in early Impella initiation.

A successful cardiac transplant in a patient with situs inversus totalis and congenitally corrected transposition of the great arteries.

A heart transplant is the gold standard therapy for patients with end-stage heart failure. In this case report, situs inversus totalis and congenitally corrected transposition of the great arteries led to a unique and complex preoperative setting. Extended donor organ harvesting, donor graft rotation of 45° to the right and post-operative stenting of the superior vena cava were essential steps in the interdisciplinary management of this case. The patient was transferred to the intensive care unit with moderate inotropic support. He was discharged to rehabilitation on postoperative day 89 and eventually underwent an additional renal transplant 14 months after the cardiac transplant.

Pioglitazone treatment mitigates cardiovascular bioprosthetic degeneration in a chronic kidney disease model.

Aims: Chronic kidney disease (CKD) is a risk factor for the development of cardiovascular diseases, e.g., atherosclerosis and calcific aortic valve disease, leading inevitably to valve replacement surgery. CKD patients with bioprosthetic cardiovascular grafts, in turn, have a higher risk of premature graft degeneration. Peroxisome proliferator-activated receptor gamma (PPARγ) activation by pioglitazone has cardio-renal protective properties, and research using a heterotopic valve implantation model has shown anti-degenerative effects of PPARγ activation on bioprosthetic valved grafts (BVG) in rats. The present work aims to analyze a potential protective effect of pioglitazone treatment on BVG in an adenine-induced rat model of CKD. Methods and Results: BVG of Sprague Dawley rats were heterotopically implanted in Wistar rats in an infrarenal position for 4 and 8 weeks. Animals were distributed into three groups for each time point: 1) control group receiving standard chow, 2) CKD group receiving 0.25% adenine and 3) CKD + pioglitazone group (300 mg per kg of 0.25% adenine chow). BVG function was analyzed by echocardiography. Plasma analytes were determined and explanted grafts were analyzed by semi-quantitative real-time PCR, Western blot analysis, histology and immunohistology.PPARγ activation significantly reduced CKD-induced calcification of aortic and valvular segments of BVG by 44% and 53%, respectively. Pioglitazone treatment significantly also reduced CKD-induced intima hyperplasia by 60%. Plasma analysis revealed significantly attenuated potassium and phosphate levels after pioglitazone treatment. Moreover, PPARγ activation led to significantly decreased interleukin-6 gene expression (by 57%) in BVG compared to CKD animals. Pioglitazone treatment leads to functional improvement of BVG. Conclusion: This study broadens the understanding of the potential value of PPARγ activation in cardio-renal diseases and delineates pioglitazone treatment as a valuable option to prevent bioprosthetic graft failure in CKD. Further mechanistic studies, e.g., using small molecules activating PPARγ signaling pathways, are necessary for the evaluation of involved mechanisms. Additionally, the translation into pre-clinical studies using large animals is intended as the next research project.

In vitro and in vivo evaluation of biohybrid tissue-engineered vascular grafts with transformative 1H/19F MRI traceable scaffolds.

Biohybrid tissue-engineered vascular grafts (TEVGs) promise long-term durability due to their ability to adapt to hosts' needs. However, the latter calls for sensitive non-invasive imaging approaches to longitudinally monitor their functionality, integrity, and positioning. Here, we present an imaging approach comprising the labeling of non-degradable and degradable TEVGs' components for their in vitro and in vivo monitoring by hybrid 1H/19F MRI. TEVGs (inner diameter 1.5 mm) consisted of biodegradable poly(lactic-co-glycolic acid) (PLGA) fibers passively incorporating superparamagnetic iron oxide nanoparticles (SPIONs), non-degradable polyvinylidene fluoride scaffolds labeled with highly fluorinated thermoplastic polyurethane (19F-TPU) fibers, a smooth muscle cells containing fibrin blend, and endothelial cells. 1H/19F MRI of TEVGs in bioreactors, and after subcutaneous and infrarenal implantation in rats, revealed that PLGA degradation could be faithfully monitored by the decreasing SPIONs signal. The 19F signal of 19F-TPU remained constant over weeks. PLGA degradation was compensated by cells' collagen and α-smooth-muscle-actin deposition. Interestingly, only TEVGs implanted on the abdominal aorta contained elastin. XTT and histology proved that our imaging markers did not influence extracellular matrix deposition and host immune reaction. This concept of non-invasive longitudinal assessment of cardiovascular implants using 1H/19F MRI might be applicable to various biohybrid tissue-engineered implants, facilitating their clinical translation.

Combining aortic arch dissection stent implantation and root surgery for aortic dissection type A.

BACKGROUND: Acute aortic dissection type A (AADA) is associated with high perioperative morbidity and mortality. A novel non-covered hybrid prosthesis (AMDS, CryoLife, Kennesaw, USA) can be easily implanted to stabilize the true lumen. However, the role of AMDS for patients requiring additional aortic root surgery has not been described. METHODS: Between 2010 and 2020 a total of n = 370 patients underwent surgery for AADA in our department. Of those, n = 120 underwent treatment for aortic root in addition to proximal arch replacement without resection of the aorta beyond the innominate artery (Control, n = 111) and were compared to patients who received additional AMDS implantation (AMDS, n = 9). RESULTS: Aortic valve repair was performed in 48.6% (Control) and in 55.6% of AMDS patients. Cardiopulmonary bypass (Control: 248 ± 76 min, AMDS: 313 ± 53 min, P < 0.01) time as well as circulatory arrest time of the lower body (Control: 30 ± 15 min, AMDS: 52 ± 12 min, P < 0.01) was prolonged in the AMDS group. Nevertheless, postoperative in-hospital morbidity such as dialysis (Control: 22.4%, AMDS: 11.1%, P = 0.68) and stroke (Control: 17.0%, AMDS: 22.2%, P = 0.65) were comparable. In-hospital death (Control: 21.8%, AMDS: 11.1%, P = 0.68) and the compound end-point MACCE (Control: 38.7%, AMDS: 44.4%, P = 0.74) did also not differ. CONCLUSIONS: Addressing the arch by implantation of AMDS prolongs cardiopulmonary bypass and circulatory arrest time, however without relevant impairments of short-term outcome. Combining root surgery with replacement of the proximal aortic arch and AMDS implantation seems feasible and safe as it did not impair the early postoperative outcome.