Post Implantation Research Articles

Antithrombotic Management for Transcatheter Aortic Valve Implantation.

There have been significant changes in the optimal antithrombotic regimen post transcatheter aortic valve implantation (TAVI) after the results of major clinical trials in the past few years. Given the clinical importance of the optimal antithrombotic therapy post TAVI, we performed a narrative description of the major clinical trials behind the scientific evidence supporting these changes, as well the current guideline recommendations and knowledge gaps. We performed a narrative description of the major clinical trials behind the scientific evidence supporting these changes. We used PubMed as a major source to collect the major clinical trials including the following key words: "transcatheter aortic valve replacement", "transcatheter aortic valve implantation", "antithrombotic", "antiplatelet" and "anticoagulation". We selected the major clinical trials on this topic. This is not a systematic review or meta-analysis. We describe the results of the major clinical trials on antithrombotic therapy post TAVI: POPULAR-TAVI A, POPULAR-TAVI B, ENVISAGE-TAVI AF, GALILEO, ATLANTIS and ADAPT-TAVR trials. Based on the results of these trials, single antiplatelet therapy is recommended post TAVI in patients without concomitant indication for oral anticoagulation or dual antiplatelet therapy, especially in elderly patients. In younger patients, it is advised to evaluate the patient's bleeding and thrombotic risk, and dual antiplatelet therapy may be reasonable in patients with a high thrombotic risk and low bleeding risk. In patients with a concurrent indication for oral anticoagulation or dual antiplatelet therapy, it is recommended to continue oral anticoagulation or dual antiplatelet therapy post TAVI. In most patients without concomitant indication for oral anticoagulation, single antiplatelet therapy is recommended post TAVI.

MTOR hypoactivity leads to trophectoderm cell failure by enhancing lysosomal activation and disrupting the cytoskeleton in preimplantation embryo

BackgroundMetabolic homeostasis is closely related to early impairment of cell fate determination and embryo development. The protein kinase mechanistic target of rapamycin (mTOR) is a key regulator of cellular metabolism in the body. Inhibition of mTOR signaling in early embryo causes postimplantation development failure, yet the mechanisms are still poorly understood.MethodsPregnancy mice and preimplantation mouse embryo were treated with mTOR inhibitor in vivo and in vitro respectively, and subsequently examined the blastocyst formation, implantation, and post-implantation development. We used immunofluorescence staining, RNA-Seq smart2, and genome-wide bisulfite sequencing technologies to investigate the impact of mTOR inhibitors on the quality, cell fate determination, and molecular alterations in developing embryos.ResultsWe showed mTOR suppression during preimplantation decreases the rate of blastocyst formation and the competency of implantation, impairs the post implantation embryonic development. We discovered that blocking mTOR signaling negatively affected the transformation of 8-cell embryos into blastocysts and caused various deficiencies in blastocyst quality. These included problems with compromised trophectoderm cell differentiation, as well as disruptions in cell fate specification. mTOR suppression significantly affected the transcription and DNA methylation of embryos. Treatment with mTOR inhibitors increase lysosomal activation and disrupts the organization and dynamics of the actin cytoskeleton in blastocysts.ConclusionsThese results demonstrate that mTOR plays a crucial role in 8-cell to blastocyst transition and safeguards embryo quality during early embryo development.

Temporal Trends in Patient Characteristics and Outcomes of Transcatheter Aortic Valve Implantation and Surgical Aortic Valve Replacement: A Nationwide Study

With increased use of transcatheter aortic valve implantation (TAVI) in treatment of aortic stenosis, it is important to evaluate real life data trends in outcomes. This nationwide register-based study aims to present an outlook on temporal trends in characteristics and outcomes including mortality.First-time consecutive Danish TAVI patients from 2010-2019 were included in this study.Chi square and Kruskal-Wallis tests were performed to assess differences in characteristics over time and Cochrane-Armitage trend tests were used to examine changes in complications and mortality.Between 2010-2019, 4,847 patients (54.6% men, median age 82 (Q1-Q3: 77 to 85)) underwent first-time TAVI. Statistically significant decrease over time was observed for pre-procedural hypertension, ischemic heart disease and heart failure (HF), while preexisting chronic obstructive lung disease and pre-procedural pacemaker (PM) remained stable.We observed a significant decrease in 30- and 90-day post operative PM implantation from 2011 to 2017 with 15.1% and 15.9% in 2011 and 8.6% and 8.9% in 2017, respectively.Incidence of HF for 30- and 90-day significantly decreased from 19.3% and 20.3% to 8.5% and 9.1%.We observed significant changes for 30-day atrial fibrillation (AF) while the changes over time for 90-day AF and 30- and 90-day stroke/transient ischemic attack (TIA) remained insignificant.All-cause mortality within 30- and 90-days significantly decreased over time from 6.7% and 9.2% in 2011 to 1.5% and 2.7% in 2019 and 2016.In conclusion this national study provides general insight on trends in complications and mortality of TAVI, demonstrating significant reductions over time.

EXTH-52. LONG-ACTING RECOMBINANT INTERLEUKIN-7, NT-I7, IMPROVES SURVIVAL FOLLOWING ONCOLYTIC ZIKA VIRUS TREATMENT IN THE SB28 IMMUNOSUPPRESSIVE AND TREATMENT-RESISTANT MURINE GLIOMA MODEL

Abstract Glioblastoma (GBM) does not respond to immunotherapy for several reasons, including limited cancer-specific neoantigens and poor T-cell infiltration. The SB28 murine glioma model recapitulates these aspects of human GBM. Zika virus (ZIKV) treatment of GL261 and CT2A-bearing mice resulted in significant survival improvement through multiple mechanisms, including direct tumor killing and induction of a local CD8+ T-cell anti-tumor response, but ZIKV is less effective against SB28 tumors. Previously, we published that a long-acting human IL-7, rhIL-7-hyFc (NT-I7, efineptakin alfa; NeoImmuneTech Inc.), increases T-cell abundance and improves tumor infiltration. Therefore, we hypothesize that combining NT-I7 with oncolytic ZIKV therapy will enhance the anti-tumor response and improve survival in mice bearing SB28 syngeneic tumors. 1×103 SB28 tumor cells were intracranially implanted in C57BL/6J mice. Mice were treated with NT-I7 on post tumor implantation day 7 and 10, followed by intratumoral ZIKV on day 14. Tumor burden was assessed using bioluminescence imaging; mice were monitored for survival and bled weekly to assess the systemic T-cell response to NT-I7. Subcutaneous injection of NT-I7 significantly boosted systemic T-cell abundance compared to control (5,623 cells/uL vs. 136 cells/uL, p < 0.05), particularly cytotoxic CD8+ T-cells (4,776 cells/uL vs. 47 cells/uL, p < 0.05). This increased abundance of CD8+ T-cells peaked at 7 days after initial treatment and persisted for 21 days. NT-I7 monotherapy did not confer any survival benefit. However, the combination of NT-I7 and ZIKV treatment resulted in significant improvement in survival compared to NT-I7 or ZIKV treatment alone (p < 0.05). Treatment with NT-I7 primes the immune system by expanding the circulating CD8+ T-cell population by 100-fold. Timing the oncolytic ZIKV injection with the peak in peripheral CD8+ T-cells greatly improved survival in the immunotherapy resistant SB28 glioma model. These data suggest a role for NT-I7 as an adjunct to various T-cell mediated treatment strategies for GBM.

Device specific quality of life in subcutaneous versus transvenous implantable cardioverter defibrillator implantations: results from the ATLAS multi-centre randomized controlled trial

Abstract Background Newer innovative subcutaneous implantable cardioverter defibrillators (S-ICDs) offer an alternative to transverse ICDs (TV-ICDs), placing leads outside of the heart thereby potentially reducing lead-related complications. The ATLAS trial, a multi-centre randomized controlled trial, showed a significant reduction in perioperative complications in TV-ICD versus S-ICD patients. The following results report device-related quality-of-life (QoL) measured in the trial. QoL measures are recognized as key patient-reported outcome measures (PROMs). Purpose To compare TV-ICD and S-ICD post implantation device-related QoL in the ATLAS trial. Methods Sample included all randomized ATLAS trial patients. The Florida Patient Acceptance Survey (FPAS) was completed at 1- and 6-months post implantation. The FPAS includes a total score and 4 subscale scores; 1) return to function, 2) device-related distress, 3) positive appraisal, and 4) body image concerns. Scores are scaled from 0-100, with total scores below 63 suggesting poor device acceptance. The primary analysis was based on complete cases and used analysis of covariance (ANCOVA) with 6-month scores as the dependent variable, group as the independent variable, and 1-month FPAS scores as the covariate. Change in FPAS total score over time within each group was explored using paired t-tests. Results There were 252 TV-ICD and 251 S-ICD patients enrolled in the main ATLAS trial, and of these, in the present analysis, 404 patients (197 TV-ICD; 207 S-ICD) had complete FPAS data. Sample mean age (SD) was 49.31 (11.54) years, males (74.3%) and Caucasian (83.7%). There were no substantive differences in patient characteristics between groups. The primary analyses found no differences between TV-ICD and S-ICD groups for FPAS total score (Mean Difference=-0.75; 95% CI, -3.15, 1.66; p=0.510) or FPAS subscale scores. Mean FPAS total scores increased from 74.43 (15.35) to 78.25 (15.88) and 73.73 (16.09) to 77.05 (16.13) between 1-month and 6-months in the TV-ICD and S-ICD groups respectively. The increase from 1-month to 6-months was statistically significant in both groups (p< 0.001). These findings suggest that regardless of ICD type, there is device acceptance in both groups from implantation and over time. Conclusion Analysis of the FPAS measure, a device-specific QoL measure, found both TV-ICD and S-ICD patients reported good acceptance of their devices, with no significant differences between groups for up to 6 months post implantation. These findings provide an important piece to the TV-ICD versus S-ICD line of inquiry in ICD patient populations particularly for this newer S-ICD innovation and can be included in decision making between health professionals and patients.

The lived experience of patients with left ventricular assist devices: a systematic review of qualitative studies

Abstract Background although the utilization of left ventricular assist devices (LVADs) in heart failure (HF) patients has been increasing, little is known about the patients’ experience of living and managing daily life post LVAD implantation. Knowing more about the patients’ experience would help LVAD nurses establish a less hierarchical and more meaningful therapeutic relationship with their patients, and anticipate the patients’ physical, emotional and social needs post LVAD implantation. Purpose to identify the themes and patterns amongst individuals with HF who have opted for LVAD implantation, as very few studies have looked at the needs of this patient group. Methods a systematic search of PubMed, Scopus, ScienceDirect and Google Scholar in November 2022 yielded 530 research papers from 2011-2022 with keywords: LVAD, left-assist, patient, qualitative. All studies were imported into Covidence, 24 duplicates were removed, and 506 papers were subjected to abstract, title and full-text screening by three researchers independently. Screening resulted in the inclusion of 15 qualitative studies on the experiences of adult patients with implanted LVAD. All studies that were included had conducted qualitative interviews. Each study was scored according to CASP criteria, and no distinction was made between Bridge-To-Transplantation Therapy and Destination Therapy. Results Fifteen [n=15] studies in 7 countries involving 296 individuals (232 patients and 64 informal caregivers) were reviewed. The review of the literature revealed a variety of findings. Data analysis identified seven themes pertaining to the experience of living with LVAD: a) physical and functional dimensions of life [n=7 studies], b) emotional – psychological dimensions [n=10 studies], c) hope and optimism [n=5 studies] d) social aspects and relations to others [n=6 studies], e) adaptation and coping mechanisms [n=6 studies], f) receiving support from others as part of holistic care [n=3 studies], and g) liminality and ambivalence [n=3 studies]. Conclusions LVAD patients experience a life with functional limitations, fear, lifestyle changes, frustration, with "up and down-ness", that requires them to resort to a repertoire of adaptation and coping mechanisms, hope, and support from family and services. LVAD implantation introduces them to a new embodied experience of living with stigma, but also to a feeling that they have been "saved". Somewhere along their "LVAD trajectory", they experience loss of identity and "liminality", and they go through what is also known as "biographical disruption". Professionals in LVAD and Heart Failure services would be better suited to support patients and their caregivers through this journey of life transformation and ambivalence, if they were more aware of the aforementioned findings. This review sheds light on the experience of a very unique group of patients, who need specialist and needs-specific care in this post-modernism biotechnical era.PRISMA Flow DiagramTable of the included studies

Patient-specific computer modelling to predict anatomical risk factors preventing post transcatheter aortic valve implantation coronary re-access in bicuspid aortic valve; a modelling study

Abstract Background Post Transcatheter aortic valve implantation (TAVI) coronary re-access is predicted to become more common as TAVI expands into lower risk cohorts. The use of a self-expanding valve (SEV) has been recognised as an independent predictor for unsuccessful coronary cannulation. Other predictors include reduced transcatheter heart valve (THV) to coronary distance and small sino-tubular junction. Despite this however a patient cohort remains in which the use of a SEV is preferable due to anatomical complexity or extensive calcification. Purpose Using patient-specific computer modelling, we aimed to assess how the deployment of different sized THVs and at different depths affected the distance from valve to coronary and valve to sino-tubular junction in bicuspid aortic valve cases. Methods In this modelling study we have used pre-procedural, CT-derived, patient-specific finite element analysis computer models to predict the eventual valve result. We studied two anatomical measures for both right and left coronary sinuses. The distance from coronary ostium to nearest structure, either THV or displaced native leaflet – Sinus of Valsalva (SoV) free space. The second distance was from the STJ to THV – STJ free space. THVs were modelled at both high and medium implant positions. THV size was based upon annular dimensions. Where the annular dimensions fell near an anatomical grey-zone, a second size THV was modelled. For each patient and measure, a mean of all distances was calculated, in addition to both minimum and maximum distances. Results The free space SOV left main coronary artery (LMCA) mean was 6.39 mm (4.87-7.91 mm). The difference between maximum and minimum was 0.9461 mm (0.54–1.36 mm), p<0.01. The largest patient-specific difference between minimum and maximum was 2.41 mm, using the same THV size but at different depths. The free space SOV right coronary artery (RCA) mean was 5.73 mm (4.17-7.30 mm). The difference between maximum and minimum was 0.789 mm (0.49-1.09 mm), p<0.01. The STJ free space LMCA mean was 4.3 mm (2.35–6.27 mm), The difference between maximum and minimum was 0.99 mm (0.63-1.35 mm), p<0.01. The STJ free space RCA mean was 3.76 mm (2.2-5.32 mm).The difference between maximum and minimum was 1.18 mm (0.9-1.56 mm), p<0.01. The largest patient-specific difference between minimum and maximum was 2.02 mm, using the same valve size but at different depths. Data presented as mean (95% confidence intervals), n=16 patients/48 models. Conclusions This modelling study has indicated a significant difference in all four measured parameters when different THVs are modelled at different depths. Note some of the largest differences are seen with the same size THV but at a different depth. We would highlight the small mean effect size seen across the results, however in cases where the difference is >2mm, this could have an effect on coronary re-access and warrants further investigation.

Evidence of early bioprosthetic valve dysfunction after TAVR in aortic valve stenosis during one-year follow-up according to VARC-3

Abstract Objectives Transcatheter aortic valve replacement (TAVR) has become a frequent treatment method for severe aortic stenosis and has increased significantly in younger patients and at lower surgical risk. Therefore, long-time considerations and the performance of TAVR devices are highly interesting. The Valve Academic Research Consortium 3 endpoint definitions (VARC-3) were released recently, offering updated and clear classifications of bioprosthetic valve dysfunction (BVD). In this retrospective multicenter study, we aimed to assess the prevalence of BVD during one-year follow-up and potential differences between self-expandable (SEV) and balloon-expandable valves (BEV). Methods Underlying conditions were evaluated by univariate analysis. Normality was tested using the Shapiro-Wilk normality test. The primary clinical endpoint was defined as immediate failure in device success, secondary endpoints were defined as prevalence of BVD during one year FU and composite endpoints according to VARC-3. Results The final study cohort consisted of 1478 patients from three tertiary care centers that underwent TAVR between 01/2015 and 12/2018. Mean Follow-up (FU) was 361 ± 26 days. During this time span overall BVD was documented in one-fourth of all patients (-BVD[-]: n=1090 (73.7%); BVD[+]: n=388; 26.3%). Further discrimination into the four main categories of BVD presented following results: Structural valve deterioration (SVD) n=142 (9.6%), Non-Structural valve deterioration (NSVD) n=235 (15.9%), hypo-attenuated leaflet thickening n=18 (1.2 %), and endocarditis n=31 (2.1%). Two-thirds of all events were identified within 30-days post implantation, accounting for new-onset of BVD during time course in one-third of all documented BVD. Device success was significantly lower in the +BVD cohort (80.6% vs. 70.1%, p<0.01*). When comparing SEV and BEV, there were significant differences in overall BVD at 30-days post implantation (13.8% vs 18.5%, p<0.01*), as well as in device success (74.1% vs. 81.5%, p<0.01*), early safety (63.8% vs. 69.8%, p=0.014) and clinical efficacy (94.1% vs. 89.9%, p<0.01*). Again, discrimination into the four main categories of BVD showed differences in NSVD at 30-days post implantation (9.8% vs. 14.3%, p<0.01*) as well as at 1-year FU (7.6% vs 14.8%, p<0.01*). Conclusion In this large retrospective multicenter study, we could observe that NSVD was the BVD category most frequently detected after TAVR in tricuspid aortic valves during 1-year FU. NSVD occurred mainly within 30 days post-implantation in patients with balloon-expandable valves, being one factor that significantly diminished device success, early safety, and clinical efficacy.

A novel self-gripping long-term resorbable mesh providing temporary support for open primary ventral and incisional hernia

A novel synthetic fully long-term resorbable self-gripping mesh has been recently developed to reinforce soft tissue where weakness exists during ventral hernia repair open procedures. This resorbable mesh is a macroporous, knitted, poly-L-lactide, poly-trimethylene carbonate copolymer monofilament mesh with the ProGrip™ technology, providing grips on one side of the mesh. A new poly-L-lactide, poly-trimethylene copolymer was developed to provide the required features for mechanical support during at least 20 weeks covering the critical healing period, including resistance to fatigue under cyclic loading conditions, as it occurs in patients. The yarns and mesh initial physical and biomechanical properties were characterized. Then, the mesh mechanical strength was evaluated over time. The mechanical properties of the proposed mesh were found to be above the generally recognized threshold value to mechanically support the repair site of a hernia over a 20-week period during in-vitro cyclic loading test. The mesh performance was evaluated in vivo using a published preclinical porcine model of hernia repair at 4-, 12- and 20-weeks post implantation. The burst strength of the hernia repair sites reinforced with the new mesh were higher at 4 & 12 weeks and comparable at 20 weeks to the one of the native abdominal walls. At all time points, the mesh was well tolerated with moderate inflammation and was fast integrated in the abdominal wall at 4 weeks. Particularly, the grips were nicely engulfed in the newly formed connective tissue. They must facilitate the anchoring of the mesh by their extension from the mesh and their mushroom shape. The preclinical data of the self-gripping resorbable mesh suggests that it has all the favorable characteristics for future clinical use during ventral hernia repair open procedures.Graphical

Abstract 13899: Engineered Tissue Graft Electrically Couples With Swine Host Heart

Introduction: Adult mammalian hearts are unable to replenish myocytes lost in myocardial infarction (MI). Recent therapies that implant myocytes derived from human induced pluripotent stem cells (hiPSC-CMs) have shown structural integration of the graft, improved cardiac function, and reduced scar size. However, to successfully remuscularize the heart, implanted tissue must integrate electrically. Here, we directly image electrical coupling between engineered grafts and the host. Methods: We created anterior LV MI in 3 immunosuppressed pigs using ischemia-reperfusion. Cardiac spheroids engineered from hiPSC-CMs were implanted into the border zone right after the procedure. Spheroids were transfected with a calcium indicator (GCaMP6). One week post implantation, the animal was sacrificed, and 0.6 mm thick slices of myocardium containing spheroids were obtained (Fig. A). The slices were stained with a voltage-sensitive dye (VSD) for optical mapping. GCaMP6 and the VSD have different emission spectra allowing electrical activation of the host tissue and spheroids to be imaged independently. The slices were activated with both global field stimuli and focal stimuli applied distant from the spheroids. Results: During field stimulation, action potentials in the slice and calcium transients (CaT) in the spheroids were simultaneous. However, during focal pacing, there was propagation across the slices and latency between the pacing pulses and spheroid CaTs (Fig. B, C). This indicates spheroid activation arose from electrical coupling with the host myocardium and not from direct stimulation by the pacing pulse. We observed coupling at 12 spheroid sites in 10 slices. At 6 sites, 1:1 coupling could be maintained at pacing rates up to 4 Hz (Fig. D). Conclusions: To our knowledge, this is the first demonstration of swine host myocardium coupling electrically with a human engineered tissue graft. Coupling occurred within 1 week and enabled the host to drive the graft.

Abstract 16826: A Rare Case of an Emergent Third Valve in Valve Intervention

Introduction: Bioprosthetic valves are prone to structural degeneration due to an average lifetime of 10-15 years. Valve in Valve (VIV) TAVR has become an alternative to the high-risk surgical patients as the growing number of successful bioprosthetic valve placements and the deteriorations over time. Emergent VIV intervention effectiveness with prior multiple artificial valves is less studied. Hypothesis: We report a case of a 54-year-old male presenting with obstructive shock with history of substance abuse and bicuspid aortic valve status post bioprosthetic aortic valve with aortic root repair at age of 15(1983), aortic stenosis requiring repeat surgical bioprosthetic Aortic Valve Replacement (SAVR) (25 mm) at age 42(2011). Recalcitrant cardiogenic shock despite vasopressor. Emergent Heart catheterization showed mild coronary artery disease (CAD) and severe cardiomyopathy, Left Ventricle ejection Fraction 15-20%. Aortic valve Gradient was 80 mmHg. Transesophageal Echocardiography (TEE) ruled out endocarditis. Impella CP and Swan-Ganz catheter were placed for hemodynamic support and monitoring. Methods: The Heart Team approach was followed. Patient was at high risk of mortality and operative complications with redo sternotomy. He subsequently underwent valve in valve TAVR with self-expanding 26 mm valve. Prior surgical valve did not require fracturing post implantation. Results: Post Trans Aortic Valve Replacement (TAVR) the mean gradient on echocardiogram decreased to 10 mmHg and LVEF recovered to 55-60%. The patient was successfully weaned off Vaso-pressors and eventually discharged home. Conclusion: Most common cause of transcatheter bioprosthetic valve failure is stenosis from calcification and thrombosis. VIV TAVR in recent studies has proven to be safe with favorable outcomes. Our patient had already undergone two surgical valve interventions, presented with critical bioprosthetic valve stenosis requiring salvage TAVR for cardiogenic shock. After the Heart team approach, TAVR was opted as a more favorable option for the patient. Although, the life of a bioprosthetic valve results in multiple interventions but overall valve in Valve technique has been proven to provide expected results in emergent high-risk patients.

75 Mood and Quality of Life after Responsive Neurostimulation (RNS) in Epilepsy Patients

Objective:Poor mood and quality of life is common among patients with medically intractable seizures. Many of these patients are not candidates for seizure focus resection and continue to receive standard medical care. Responsive neurostimulation (RNS) has been an effective approach to reduce seizure frequency for nonsurgical candidates. Previous research using RNS clinical trial participants has demonstrated improved mood and quality of life when patients received RNS-implantation earlier in their medically resistant epilepsy work-up (Loring et al., 2021). We aimed to describe the level of depression and quality of life in adults with medical resistant epilepsy, treated with RNS, presenting to an outpatient clinic.Participants and Methods:This pilot study was conducted among 11 adult epilepsy patients treated with RNS at the epilepsy specialty clinic at Baylor College of Medicine. Ages of participants ranged from 18-56 (M=32.01, SD=12.37) with a mean education of 12.43 (SD=0.85). The majority of the participants identified as White (White=72.2%; Hispanic/Latino/a=14.3%, Other=7.1%). We also present pre- and post-RNS preliminary results of a subset of 4 patients for whom pre and post implantation data was available. Depression symptoms were assessed through the Beck Depression Inventory, 2nd Edition (BDI-II) and quality of life was determined using the Quality of Life in Epilepsy (QoLiE-31).Results:Patients reported minimal symptoms of depression (M=5.45, SD=4.03) and good overall quality of life (M=71.18, SD=14.83) after RNS. Participants’ scores on their overall quality of life ranged from 50 to 95 (100=better quality of life). The QoLiE-31 showed high scores on emotional wellbeing (M=69.45, SD=14.56) and cognitive functioning (M=65.36, SD=16.66) domains. Post-hoc analysis revealed a significant difference in the cognitive functioning domain of QoLiE-31 before (M=44.75, SD=12.58) and after (M=51.0, SD=11.58) RNS implantation(t(3)=-3.78, p=0.016. Additionally, overall QoLiE score approached statistical significance when comparing pre-RNS (M=44.75 SD=9.29) to post-RNS (M=49.75 SD=11.62; t(3)=-2.01, p = 0.069). No significant differences were evident on seizure worry, energy/fatigue, medication effects, and social functioning domains of QoLiE-31 before and after RNS treatment.Conclusions:These pilot study results suggest low levels of depression with this population post-RNS implantation. Additionally, there is preliminary evidence to suggest improved patient-rated cognitive functioning and overall quality of life. While this is a small study population, the results have important implications for patients with intractable epilepsy, even with those form who surgical resection may not be possible. Future studies with large enough samples to examine moderating and mediating factors to mood and quality of life changes post-RNS will be important.

How Porcine Acellular Dermal Matrix Influences the Development of the Breast Capsule 1 Year after Implantation: A Histopathological Analysis.

In prepectoral breast reconstruction (PPBR) the acellular dermal matrix (ADM)'s integration capacity into the tissue is known. The aim of this study was to analyze the effect of the ADM on development and composition of the peri-implant breast capsule in a dynamic setting of breast tissue expansion during two-stage prepectoral breast reconstruction. This is a prospective single-center study in which 50 patients who underwent mastectomy and breast reconstruction with prepectoral tissue expander and Braxon ADM (group A) and submuscular tissue expander (group B) were enrolled. One-year post implantation hematoxylin & eosin (H&E) staining and immunohistochemistry analyses were done on capsule tissue samples. The analysis conducted on H&E-stained samples showed a significant reduction of cellular density and a decrease of the cellular infiltration in capsules of ADM-covered expanders compared with naked expander capsules (P < 0.05). The immunohistochemical analyses showed that group A capsules presented significantly less M1 CD68+ macrophages (P < 0.05), lower alfa-SMA expression levels, and a lower number of myofibroblasts (P < 0.05) compared with group B capsules. Presence of lymphatic vessels was minimally detected in both groups. The ADM presence around the prepectoral tissue expander influences the development of the peri-implant capsule, causing a significant reduction of the number of cells and inflammatory infiltrate, especially M1 macrophages and myofibroblasts. The ADM Braxon is therefore effective in creating a noninflamed capsule around the implant and in dynamic tissue conditions, and such an environment is maintained in time.

Mechanical pump complication after HeartMate 3 implantation.

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

The role of intravascular imaging in chronic total occlusion percutaneous coronary intervention.

Chronic total occlusions (CTOs) represent the most complex subset of coronary artery disease and therefore careful planning of CTO percutaneous coronary recanalization (PCI) strategy is of paramount importance aiming to achieve procedural success, and improve patient's safety and post CTO PCI outcomes. Intravascular imaging has an essential role in facilitating CTO PCΙ. First, intravascular ultrasound (IVUS), due to its higher penetration depth compared to optical coherence tomography (OCT), and the additional capacity of real-time imaging without need for contrast injection is considered the preferred imaging modality for CTO PCI. Secondly, IVUS can be used to resolve proximal cap ambiguity, facilitate wire re-entry when dissection and re-entry strategies are applied and most importantly to guide stent deployment and optimization post implantation. The role of OCT during CTO PCI is currently limited to stent sizing and optimization, however, due to its high spatial resolution, OCT is ideal for detecting stent edge dissections and strut malapposition. In this review, we describe the use of intravascular imaging for lesion crossing, plaque characterization and wire tracking, extra- or intra-plaque, and stent sizing and optimization during CTO PCI and summarize the findings of the major studies in this field.

Intraprocedural versus next day transthoracic echocardiography following minimalist transfemoral TAVI

BackgroundRoutine pre-discharge echocardiography (ECHO) is recommended post transcatheter aortic valve implantation (TAVI) as a baseline for future comparison. However, there is no clear guidance on the optimal timing of this study.AimThe purpose of this retrospective study was to investigate the safety and work-force efficiency of intraprocedural same-day ECHO versus next-day ECHO, following transfemoral TAVI.Methods and resultsIn this retrospective study 100 consecutive patients who underwent intraprocedural ECHO only were compared with 100 consecutive patients undergoing both intraprocedural and routine next-day ECHO following elective transfemoral TAVI. All patients received the Sapien 3/Ultra transcatheter heart valve and were treated with a minimalist procedure with conscious sedation. The composite of in-hospital mortality, urgent ECHO and new tamponade after leaving the cath lab and before discharge was not different between the two groups (4 vs. 4%, P = 1). There was no paravalvular leak more than mild in any of the cases. Length of stay was similar (1 day).ConclusionsIntraprocedural post-TAVI ECHO appears as safe as next day pre-discharge ECHO and obviates the need for a routine next day study, thereby reducing burden on echocardiography services and allows better utilisation of resources.

Complete human day 14 post-implantation embryo models from naive ES cells

The ability to study human post-implantation development remains limited owing to ethical and technical challenges associated with intrauterine development after implantation1. Embryo-like models with spatially organized morphogenesis and structure of all defining embryonic and extra-embryonic tissues of the post-implantation human conceptus (that is, the embryonic disc, the bilaminar disc, the yolk sac, the chorionic sac and the surrounding trophoblast layer) remain lacking1,2. Mouse naive embryonic stem cells have recently been shown to give rise to embryonic and extra-embryonic stem cells capable of self-assembling into post-gastrulation structured stem-cell-based embryo models with spatially organized morphogenesis (called SEMs)3. Here we extend those findings to humans using only genetically unmodified human naive embryonic stem cells (cultured in human enhanced naive stem cell medium conditions)4. Such human fully integrated and complete SEMs recapitulate the organization of nearly all known lineages and compartments of post-implantation human embryos, including the epiblast, the hypoblast, the extra-embryonic mesoderm and the trophoblast layer surrounding the latter compartments. These human complete SEMs demonstrated developmental growth dynamics that resemble key hallmarks of post-implantation stage embryogenesis up to 13–14 days after fertilization (Carnegie stage 6a). These include embryonic disc and bilaminar disc formation, epiblast lumenogenesis, polarized amniogenesis, anterior–posterior symmetry breaking, primordial germ-cell specification, polarized yolk sac with visceral and parietal endoderm formation, extra-embryonic mesoderm expansion that defines a chorionic cavity and a connecting stalk, and a trophoblast-surrounding compartment demonstrating syncytium and lacunae formation. This SEM platform will probably enable the experimental investigation of previously inaccessible windows of human early post implantation up to peri-gastrulation development.

Individualizing Medicinal Therapy Post Heart Stent Implantation: Tailoring for Patient Factors.

The field of cardiovascular medicine is undergoing a transformative shift towards personalized medicinal therapy, particularly in the context of post stent implantation. This narrative review explores the significance, challenges, and future directions of individualized treatment strategies for patients with coronary stents. The review highlights the pivotal role of personalized approaches in optimizing treatment efficacy and minimizing adverse events. Real-world clinical studies and trials underscore the importance of tailoring antiplatelet therapy based on platelet function testing, genetic testing, and risk scoring. These studies reveal that personalized medicinal treatment improves clinical outcomes by balancing preventing thrombotic events and mitigating bleeding risks. Challenges, including cost, test availability, patient adherence, and ethical considerations, are discussed in depth, shedding light on the complexities of implementing personalized approaches. Technological advancements, including omics data integration, artificial intelligence, and big data analytics, shape the future of personalized medicinal therapy. These tools enable precise pharmacogenomic selection of medications and the development of integrated risk-scoring systems. Patient engagement and education are also central, with empowered patients and remote monitoring contributing to collaborative decision-making. In conclusion, the narrative review underscores that personalized medicinal therapy post stent implantation holds immense promise for revolutionizing cardiovascular care. By embracing a comprehensive approach that considers genetics, clinical factors, and patient preferences, healthcare providers can optimize treatment outcomes and improve patient quality of life. The evolving landscape of personalized medicine offers a glimpse into a future where tailored treatment strategies become the cornerstone of precision cardiovascular care.

Impact of Different Right Ventricular Lead Positions on QRS Complex Duration Post Cardiac Resynchronization Therapy Device Implantation

Abstract Aim and objectives The aim of the study was to evaluate the effect of different RV lead positions on QRS complex duration post CRT device implantation in patients indicated for CRT as a treatment of chronic heart failure based on the recommendations of ESC guidelines for diagnosis and treatment of acute and chronic heart failure published in 2016 and to assess the effect of change of QRS complex duration and morphology according to different RV lead positions on clinical response. Patients and Methods This study included 100 patients (age 60.02 ± 7.18) post CRT device implantation presented for follow up at electrophysiology clinics of the cardiology department of Ain Shams university hospitals at least 3 months post CRT device implantation, during the period form from December 2020 till May 2021. The patients were divided into 2 groups according to the site of RV lead implantation after confirmation of the RV lead position by fluoroscope in Right anterior oblique (RAO) and left anterior oblique (LAO) views, 54 patients had the RV lead implanted in the RV Apex (RVA n = 54) and 46 patients had the RV lead implanted in the RV Septum (RVS n = 46). Results OF the total 100 patients that enrolled in our study the rate of non-responders was 19% of the patients showed no clinical improvement, no improvement of NYHA class by at least one grade, 30% of the patients were non-Echocardiographic responders, no improvement of LVEF (Δ EF) by at least 5% with no decrease of LVES diameter by at least 15%, and 15% of the patient were nonECG responders, delta QRS (ΔQRS) didn`t increase by at least 20%. There was no significant difference between the two groups regarding clinical response (NYHA class) (P-value = 0.583), LVEF (Δ EF 6.26 ± 1.64 in RVS group vs. 6.07 ± 1.67 in RVA group, P-value = 0.575) LVES diameter (47.70 ± 8.03 in RVS group vs. 45.39 ± 7.48 in RVA group, P-value = 0.141) or QRS complex narrowing (ΔQRS 60.93 ± 24.68 in RVS group vs. 54.07 ± 26.12 in RVA group, P-value = 0.182). There was no significant difference in the rate of non-responders between the two groups (clinical non responders in RVS group n = 8 vs. RVA group n = 11, P value = 0.547) (Echo non responders in RVS group n = 13 vs. RVA group n = 17, P value = 0.726) (ECG non responders in RVS group n = 6 vs. RVA group n = 9, P value = 0.613), There was an inverse relationship between ΔQRS and clinical response (NYHA) class post CRT device implantation in both RVS and RVA groups (P value 0.016 in RVS group, P value 0.007 in RVA group). Conclusion The study demonstrates that septal RV pacing in CRT is non-inferior to apical RV pacing regarding the primary objective of the study regarding clinical outcome, narrowing of QRS complex (ΔQRS) or LV reverse remodeling, thus no recommendation for optimal RV lead position can hence be drawn from this study. Also, delta QRS complex duration may be used as indicator for electric remodeling and CRT response.

ICD/CRT-D Registry Ain Shams University Hospitals

Abstract Background The idea of the ICD registry was prompted from the National Coverage Decision that was published by the Centers for Medicare and Medicaid Services (CMS) in 2005 and based on the Sudden Cardiac Death in Heart Failure Trial, Ain Shams University Hospitals aim to take the lead by documenting the first ICD/CRT-D Registry in Egypt. Aim of the Work To capture the characteristics, treatments, and outcomes of patients receiving ICDs to improve care for patients receiving ICDs and CRT-Ds in Egypt. Methods 102 consecutive patient that received an ICD/CRT-D (initial or generator change) for primary or secondary prevention of SCD and came for ICD/CRT-D follow up at Ain Shams University hospitals pacemaker outpatient clinics in a timeline of one year (7-2019 till 11-2020). Results Males were around two thirds of cases (68.6%), and more than half of cases (52%) were smokers. Implantation for primary prevention of SCD was in 58.8% of patients. Most of cases had their ICDs follow-up at a time between 1 to 3 years after implantation. HFrEF was significantly more common in primary prevention group (93.3%) of patients of primary prevention group, while IsHD was the most common comorbidity in patients that had ICD implantation for secondary prevention of SCD (66.7% of them). Total complication rate was 6.86% including, pocket hematoma occurred in 2.9% of cases, and lead dislodgment that required repositioning without a plan to add a transvenous lead occurred in 3.9% of cases. Beta Blockers and Amiodarone were the most common drugs used among patients as regard 88.2% and 65.7% respectively. VTs and NSVTs were the most frequent post implantation events among the studied cases 45.1% and 42.2% respectively. 52% of patients had ATP therapy to events, Failed ATP therapy occurred in 60% of them. 33.3% of patient received ICD shock therapy, Inappropriate Shocks was in 20.6% of them. 50.9% of the patients had a bradycardia pacing as about 34% of patient had CRT-D for pump failure. VF detection zone interval was significantly longer in primary prevention group. No significant differences according to implantation indication regarding VT2 zone interval. Regarding VT1 zone; monitor only was the mainly action in 58.7% of patients. Only 20.6% of patients had VT1 zone off. Conclusion This observational and descriptive study provides strong evidence that ICD has an effective role to improve survival in primary and secondary prevention of SCD. We noticed increase in implantation rate of ICD for primary prevention of SCD who gain great benefits from the device later on, minimal complication rate of ICD implantation.