Post Implantation Research Articles

Direct transaortic transcather valve-in-valve implantation into a mechanical aortic valve prosthesis during left ventricular assist device implantation: description of a surgical technique.

The presence of a mechanical aortic valve prosthesis is considered a relative contraindication for left ventricular assist device implantation (LVAD) due to the occurrence of thromboembolic events. Five patients were operated on for LVAD implantation with status post mechanical aortic valve implantation (n = 3 with status post Bentall procedure). After removal of the leaflets, a transcatheter balloon-expandable valve was placed within the mechanical ring in all patients. Three patients were discharged from hospital with a maximum follow-up of 3.3 years. Transaortic transcatheter valve implantation into a mechanical aortic valve during LVAD implantation is a feasible option. It reduces operative times and might also prevent thromboembolic events.

Evaluation of totally implantable catheters in healthy horses

BackgroundFor horses requiring prolonged daily cephalic intravenous regional limb perfusion (IVRLP), the use of a totally implantable catheter (TIC) could be indicated to reduce complications associated with frequent venipuncture or external catheterization. This study aims to evaluate the implantation technique of the TIC in the cephalic vein of horses for IVRLP, describe the complications associated with the device’s placement and use, and assess its viability up to 60 days after implantation. Totally implantable catheters, cut to 15 cm (n = 5) and 46 cm (n = 5) in length, were implanted into one cephalic vein in ten adult horses (n = 10). Twenty-four hours following placement, IVRLP with contrast was performed via the TIC and evaluated with radiography. Physical examinations, lameness evaluation, hematologic assessment, and the catheter patency tests were performed at scheduled intervals for the duration of catheterization (7–60 days).ResultsCatheters were implanted without difficulty and allowed for IVRLP 24 h post implantation. Complications resulted in removal of the catheters, with four maintained for 7 days, three in place for 15 days, and three catheters maintained for 60 days. Complications included lameness, limb swelling, catheter kinking, and venous thrombosis.ConclusionsThe implantation technique of the TIC in the cephalic vein of horses is feasible and requires minimal technical effort. Although TIC allows venous access without the need for repeated venipuncture, its long-term use presents complications. For horses requiring prolonged daily cephalic IVRLP, the use of a TIC could be indicated. However, the high incidence of venous thrombosis may limit clinical application.

Outcomes of remote pulmonary artery hemodynamic monitoring in heart failure patients with obstructive sleep apnea

Abstract Introduction Obstructive sleep apnea (OSA) is often associated with heart failure (HF). Remote pulmonary artery (PA) hemodynamic monitoring has shown to decrease HF related readmissions. However, there is paucity of data regarding its efficacy and mortality in patients with OSA. Purpose Real-world analysis of outcomes of remote PA hemodynamic monitoring using CardioMEMS device in reducing HF hospitalization in patients with OSA [apnea–hypopnea index (AHI) ≥5]. Methods Retrospective data was collected for patients with HF who had CardioMEMS device implanted based on FDA indications from April 2015 to August 2020. The number of hospitalizations, emergency department (ED) and HF clinic visits data was collected for 1-year pre and 1-year post device implantation. Mortality data was also collected at 1-year post-implantation. Patients who were diagnosed with OSA based on AHI ≥5 on sleep study at the time of implantation were included in the study. Analysis was done using Kruskal-Wallis test for comparison between heart failure patients with and without OSA. Mortality was compared with Pearson's chi-squared test. Results CardioMEMS device was implanted in 177 patients during the study period. Of this population, 108 (61%) patients had known OSA at the time of implantation. There was a statistically significant decrease in overall mean HF admissions from 1.80 (± 1.55) to 0.62 (± 1.07), 65.6%, p<0.001 and mean HF ED visits from 1.37 (± 1.50) to 0.5 (± 0.95), 63.5%, p<0.001 in 1-year pre- and post-implantation among OSA patients. When comparing outcomes between HF patients with and without OSA, there was no statistically significant difference observed between them in all-cause admissions, HF admissions, ED visits, ED HF visits, and HF clinic visits 1-year pre and post implantation. Also, no statistically significant difference was observed in mortality between the groups at 1-year post-implantation. Conclusions PA hemodynamic monitoring using CardioMEMS device had a net benefit in reducing HF admissions and HF ED visits in OSA patients which was similar in patients without OSA. Funding Acknowledgement Type of funding sources: None.

The effect of QRS area in predicting survival benefit following cardiac resynchronization therapy: a systematic review and meta-analysis

Abstract Background QRS area, three-dimensional QRS complex, is among novel vectorcardiographical methods of measuring the magnitude of electrical forces generated by the heart. Hypothetically, greater QRS area portrayed higher dyssynchronous electrical activation, possibly deriving significant cardiac resynchronization therapy (CRT) benefit. Previous studies suggested a positive correlation between QRS areas and the degree of CRT responses. Nevertheless, its clinical use has remained premature. We hence performed a systematic review and meta-analysis of QRS area in predicting survival benefit following CRT. Method We comprehensively searched the databases of MEDLINE, EMBASE, and Cochrane database from inception to March 2021. Included studies with prospective and retrospective cohort design. Studies those report QRS area before implantation of CRT and outcome of total mortality. Data of each study were combined with random effects model. The results were reported in hazard ration (HR) with 95% confidence intervals. Result Four observational studies, including 4,931 patients, were identified. The cut-off values between large and small QRS areas ranged from 102–116 μVs. Our analysis showed larger QRS area was statistically associated with survival benefit in patients implanted with CRT with follow up time up to 5 years (Pooled hazard ratio 0.46, 95% confident interval 0.38–0.55, I2=42%). More QRS areas changes (pre and post implantation) were associated with lower total mortality rate (Pooled hazard ratio 0.45, 95% confident interval 0.38–0.52, I2=0%). Conclusion Patients with pre-implantation larger QRS area were strongly associated with survival benefit after CRT implantation. QRS area may potentially become additional selection criteria for CRT implantation. Funding Acknowledgement Type of funding sources: None. Figure 1. Forest plot of pooled hazard ratioTable 1. Study characteristics

Long-term follow up after percutaneous PFO closure. Does baseline PFO anatomy affect the long term procedural result and the severity of residual shunt?

Abstract Background Patent foramen ovale (PFO) has been increasingly identified as a cause for left circulation thromboembolism. The risk is even higher in patients with specific anatomic features, like atrial septal aneurysm (ASA), prominent Eustachian valve and Chiari network. Transcranial Doppler with detection of high intensity signals (HITS), after injection of agitated saline, contributes to diagnosis and follow up of patients with PFO. Percutaneous PFO closure is a well-established therapy, if indicated. It remains though unclear, whether the baseline anatomy has an impact on the long-term procedural result. Purpose To investigate if there was a difference in the number of detected HITS after bubble test in patients with baseline high-risk anatomy in comparison to patients without complex features at least 1 year post-procedurally. Methods Consecutive patients, who underwent percutaneous closure, were investigated at least one year post implantation. Patients were classified in two groups according to presence or not of high-risk baseline anatomy. Every patient underwent transcranial Doppler with bubble test with agitated saline at rest and after Valsalva maneuver with documentation of HITS up to 60 sec after the straining maneuver. Results 38 consecutive patients were included (42% men) with mean age 51±12 years and a mean follow-up period of 9±3 years. At baseline 14 patients (37%) had high risk anatomy (7 patients with ASA, 3 with Chiari network and 4 with prominent eustachian valve). There was no difference between the two groups in the mean age (no high-risk: 53±11 years vs high-risk: 48±13 years, p=0.22), in the duration of follow-up period (no high-risk: 9±3 years vs high-risk: 10±2 years, p=0.66) and in other risk factors (Table). The number of documented HITS after Valsalva maneuver was significantly higher in patients with high-risk morphological features [7.50 (10.25–1.50) vs. 0.00 (0.00–3.75), p=0.003] (Figure, panel A). [bo2] Among patients with high risk features six were on prolonged antiplatelet therapy with either aspirin or P2Y12-inhibitor. Patients with high-risk features on prolonged therapy had significant lower HITS [1.00 (0.00–3.25)] compared to patients with high risk features and no prolonged antiplatelet therapy [10.00 (8.25–13.25)] (p=0.008) (Figure, panel B). Recurrent cerebrovascular accidents were similar in both groups (2 events with high-risk anatomy and 1 event without). No patient regardless of PFO morphology and antiplatelet strategy showed a significant right to left shunt (>30 HITS according to Spencer scale) Conclusion Percutaneous PFO closure is an effective therapy for paradoxical left circulation thromboembolism. Patients with high-risk anatomy may show an increased prevalence of residual, though clinically irrelevant shunt and may require a stricter follow-up. Prolonged antiplatelet therapy may reduce the number of detected microbubbles. Randomized data are required to evaluate this hypothesis. Funding Acknowledgement Type of funding sources: None. HITS-anatomy-antiplatelet therapy

Combination of CHARGE AF score and index of 24-hour electrocardiogram to predict incident atrial fibrillation and cardiovascular events

Abstract Background Atrial fibrillation (AF) is associated with increased risks of stroke and heart failure. AF risk prediction can facilitate the efficient deployment of diagnosis or interventions to prevent AF. Purpose We sought to assess the combination prediction value of Holter electrocardiogram (Holter ECG) and the CHARGE-AF score (Cohorts for Aging and Research in Genomic Epidemiology-AF) for the new-onset of AF in a single center study. We also investigated the association between clinical findings and the new-onset of cerebral cardiovascular events. Methods From January 2008 and May 2014, 1246 patients with aged≥20 undergoing Holter ECG for palpitations, dizziness, or syncope were recruited. Among them, 350 patients were enrolled in this study after exclusion of 1) AF history at the time of inspection or before, 2) post cardiac device implantation, 3) follow-up duration <1 year, and 4) no 12-lead ECG records within 6 months around Holter ECG. Results During the 5.9-year follow-up, 40 patients (11.4%) developed AF incidence. Multivariate cox regression analysis revealed that CHARGE-AF score (hazard ratio [HR]: 1.59, 95% confidence interval (95% CI): 1.13–2.26, P<0.01), BMI (HR: 0.91, 95% CI: 0.83–0.99, P=0.03), frequent supraventricular extrasystoles (SVEs) ≥1000 beats/day (HR: 4.87, 95% CI: 2.59–9.13, P<0.001) and first-degree AV block (HR: 3.52, 95% CI: 1.63–7.61, P<0.01) were significant independent predictors for newly AF. The area under the ROC curve (AUC) of the combination of the CHARGE-AF score and frequent SVEs (≥1000) was greater than the CHARGE-AF score alone (0.73, 95% CI: 0.64–0.82 vs 0.66, 95% CI: 0.56–0.75, respectively). On the ROC curve, the CHARGE-AF score of 12.9 was optimum cut-off value for newly AF. Patients with both the CHARGE-AF score≥12.9 and SVEs≥1000 developed AF at 129.0/1000 person-years, compared with those with the CHARGE-AF score<12.9 and SVEs≥1000 (48.9), the CHARGE-AF score≥12.9 and SVEs<1000 (40.0) and the CHARGE-AF score<12.9 and SVEs<1000 (7.4), respectively. In multivariate cox regression analysis, age, past history of congestive heart failure and myocardial infarction, and antihypertensive medication were significant predictors of cerebral cardiovascular events (n=43), all of which signifying the components of the CHARGE-AF score. The AUC of the combination of the CHARGE-AF score and frequent SVEs (≥1000) was not different from the CHARGE-AF score alone (0.73, 95% CI: 0.64–0.81 vs 0.73, 95% CI: 0.64–0.82, respectively). Conclusion CHARGE-AF score has higher predictive power of both the new incident AF and cerebral cardiovascular events. The combination of CHARGE-AF score and SVEs≥1000 beats/day in Holter ECG can demonstrate the additional effect of prediction ability for the new incident AF, but not for cerebral cardiovascular events. Funding Acknowledgement Type of funding sources: None.

Increased rate of new-onset left bundle branch block in patients with bicuspid aortic stenosis undergoing TAVR; data from a national registry

Abstract Background There is a growing interest in transcutaneous aortic valve replacement (TAVR) therapy among patients with bicuspid severe aortic stenosis (BAV). Conduction disturbances remain a frequent complication of TAVR, and new-onset permanent LBBB (NOP-LBBB) post-TAVR may be a marker of worse outcomes. Purpose To evaluate primarily the rate of NOP-LBBB following TAVR among patients with BAV as compared to tricuspid severe aortic stenosis (TAV). Methods Patients enrolled in the multicenter (5 centers) Bicuspid AS TAVR Registry were reviewed and compared with patients with TAV. Patients with prior aortic valve replacement, other valve morphologies and those with preprocedural LBBB or pacemaker were excluded. NOP-LBBB was defined as LBBB first detected and persisting 30-days following TAVR. Results A total of 387 patients (66 with BAV, 321 with TAV), age 80.3±7.3, 47% females were analyzed. The device success rates were 95% in both groups without any conversions to surgery. The rate of NOP-LBBB was significantly higher among patients with BAV vs. TAV (29.2% vs. 16.9%, p=0.02). However, the rate of post procedural pacemaker implantation was similar (14.8% vs. 12.5%; respectively, p=0.62). In BAV and TAV groups, 1-year mortality (6.1% vs. 7.2%; respectively, p=0.75) and stroke rates (6.1% vs. 3.5%; respectively, p=0.3) were not significantly different. Multivariate analysis identified BAV as an independent predictor of NOP-LBBB (OR=2.7, 95% CI 1.3–5.4). Furthermore, BAV subtypes with raphe (type 1) were identified as independent predictors of NOP-LBBB (OR=3.2, 95% CI: 1.5–6.7). Conclusions Patients with BAV undergoing TAVR have greater risk for developing NOP-LBBB compared with patients with TAV and the presence of raphe was associated with increased risk of NOP-LBBB. The prognostic significance for this finding warrants further evaluation in future studies. Funding Acknowledgement Type of funding sources: None.

Permanent pacemaker implantation post transcatheter aortic valve replacement- the role of pacing burden

Abstract Introduction Previous studies have provided inconsistent results regarding the clinical impact of new permanent pacemaker (PPM) post TAVR. Our aim is to evaluate whether new PPM post TAVR is associated with higher 1-year mortality and/or heart failure hospitalizations and whether pacing burden is related to adverse outcomes. Results Overall, 1245 patients underwent TAVR between the years 2008–2019 and were included in our analysis with a median follow up of 2.3 years (IQR 1–4). 191 (15%) had a new PPM implantation during index admission. Compared to patients without PPM those implanted had significantly higher 1-year mortality rate (18% vs 11%, p-0.007) as well has higher combined outcome of mortality and HF hospitalizations. There was no difference in pacing burden between survivors and non survivors in all models examined: first and last clinic visit, maximal pacing during the first-year post implantation and the difference in pacing trend between visits. Older age, peripheral artery disease (PAD) and previous myocardial infarction (MI) were independently associated with mortality or combined outcome of mortality and HF hospitalizations. Conclusion New pacemaker implantation post TAVR is associated with higher 1-year mortality and HF hospitalization, however pacing burden isn't associated with adverse clinical course. Funding Acknowledgement Type of funding sources: None.

MRI Surveillance of Plastic Material Surgical Meshes: Experimental Model - Interim Results

The number of surgical procedures for abdominal wall defects is increasing, often requiring the insertion of plastic material meshes. Surveillance of patients with inserted plastic meshes requires an accurate determination of the position of the mesh. However, this is a difficult task, depending on the kind of mesh, magnetic resonance imaging (MRI) protocol or consistence of the surrounding tissue (fat, muscle, aponeurosis). The aim of our research was to develop an experimental model to test the ability of MRI to identify the exact position of surgical plastic meshes: polypropylene or polyester. To simulate the placement of a mesh in human body we developed a model built up from two pieces of tissue with dimensions of 40 cm x 20 cm, harvested from a pig with a weight of 120 kg. The meshes were situated for MRI evaluation between the two pieces: abdominal pig muscle respectively suprajacent abdominal pig wall subcutaneous fat, approximately 2 cm high. Five surgical meshes were scanned through six MRI sequences, in view of establishing an optimal MRI scanning protocol and best visible meshes. The MRI scans were evaluated by 5 radiologists with different degrees of training. Our results showed that the experimental model developed by us can be successfully used to test the ability of MRI to visualize different kind of plastic meshes. Also, our experiment has revealed that T1fl2D sequence is the best in highlighting meshes from surrounding tissue, and the best visualized Mesh was number 4, made of polyester. In conclusion, based on our experimental model, we should select a plastic mesh or MRI protocol which will allow an optimal post implantation monitoring. Modern technology of material�s fabrication can help to better identify the mesh itself using MRI scanning.

DRIVING RESTRICTION AND EARLY ARRHYTHMIAS IN PATIENTS RECEIVING A SUBCUTANEOUS IMPLANTABLE CARDIOVERTER DEFIBRILLATOR (DREAM SICD STUDY)

BACKGROUND Subcutaneous defibrillators (SICD) are being used increasingly for selected patients. Although there are established Canadian driving guidelines post transvenous ICD implantation, none exist for SICDs. The purpose of this study is to evaluate the rate of appropriate and inappropriate therapies and sudden cardiac incapacitation (SCI) after implantation of a SICD in contemporary practice. These data will help ascertain current driving guidelines in Canada following SICD implantation. The primary endpoint was incidence of appropriate and inappropriate ICD therapy within 7 days, 14 days, 30 days, 60 days, 90 days, 180 days and one-year post SICD implantation. The secondary variable was annualized risk of harm (ARH) while driving; ARH < 0.00005 while driving is considered acceptable in Canada. METHODS AND RESULTS We performed retrospective chart reviews of consecutive patients who received a SICD at eight Canadian centers between January 1st, 2016 and May 31st, 2020, including 198 patients in the final analysis. Both primary and secondary prevention SICDs were included. We reviewed device clinic electronic medical records and charts from immediate post-implant and subsequent follow-up visits. The baseline patient demographics are described in table 1. The overall incidence of syncope was 2.5%. The adjusted incidence rate of any ICD therapy and ARH while driving remained below the acceptable risk of harm for secondary prevention patients, except in the first 7 days post implantation (Figure 2a). The ARH while driving remained below the acceptable risk for primary prevention patients at all of the time periods (Figure 2b) till 12 months of follow up. CONCLUSION The rate of appropriate ICD therapy in a contemporary patient population implanted with an SICD is very low and the ARH while driving remains below acceptable harm threshold, except in first seven days for secondary prevention population. To our knowledge, this is the first study to assess the risk of harm while driving in a contemporary patient population with SICDs. Subcutaneous defibrillators (SICD) are being used increasingly for selected patients. Although there are established Canadian driving guidelines post transvenous ICD implantation, none exist for SICDs. The purpose of this study is to evaluate the rate of appropriate and inappropriate therapies and sudden cardiac incapacitation (SCI) after implantation of a SICD in contemporary practice. These data will help ascertain current driving guidelines in Canada following SICD implantation. The primary endpoint was incidence of appropriate and inappropriate ICD therapy within 7 days, 14 days, 30 days, 60 days, 90 days, 180 days and one-year post SICD implantation. The secondary variable was annualized risk of harm (ARH) while driving; ARH < 0.00005 while driving is considered acceptable in Canada. We performed retrospective chart reviews of consecutive patients who received a SICD at eight Canadian centers between January 1st, 2016 and May 31st, 2020, including 198 patients in the final analysis. Both primary and secondary prevention SICDs were included. We reviewed device clinic electronic medical records and charts from immediate post-implant and subsequent follow-up visits. The baseline patient demographics are described in table 1. The overall incidence of syncope was 2.5%. The adjusted incidence rate of any ICD therapy and ARH while driving remained below the acceptable risk of harm for secondary prevention patients, except in the first 7 days post implantation (Figure 2a). The ARH while driving remained below the acceptable risk for primary prevention patients at all of the time periods (Figure 2b) till 12 months of follow up. The rate of appropriate ICD therapy in a contemporary patient population implanted with an SICD is very low and the ARH while driving remains below acceptable harm threshold, except in first seven days for secondary prevention population. To our knowledge, this is the first study to assess the risk of harm while driving in a contemporary patient population with SICDs.

The South African SHARE-TAVI registry: incidence and risk factors leading to conduction disturbances requiring permanent pacemaker implantation

Background: One of the most common complications post transcatheter aortic valve implantation (TAVI) is the development of heart block requiring permanent pacemaker implantation (PPM). The incidence of PPM in international registries ranges from 13% - 17.5%. Methods: The aim of this observational study was to report the PPM rate in the SHARE-TAVI registry and determine the clinical, electrocardiographic and procedural predictors of PPM as well as the effect of PPM on clinical outcomes. Results: Three hundred and fi ve subjects were analysed. The PPM rate was 9%. Third degree atrioventricular block at the time of implant was the most common indication for PPM. Self-expanding valves (PPM rate 14% vs. 6% for balloon-expandable valves, p=0.02) were correlated with the need for PPM. Baseline ECG predictors of PPM were axis deviation, QRS duration and conduction delay, most notably a pre-existing right bundle branch block (OR 15.88, p&lt;0.01). PPM infl uenced functional class at 30 days, but not the need for repeat hospitalisation or mortality at 30-day and 1-year follow-up. Conclusions: A PPM rate lower than that reported in large international registries was found. Predictors of PPM and the infl uence of PPM on outcomes were similar to those reported in the international data.

Predictors of Right ventricular Pacing induced Left Ventricular dysfunction in Pacemaker Recipients with Preserved Ejection Fraction

Abstract Background Pacemaker (PM) has been an effective treatment in the management of patients with brady-arrhythmias. Chronic RV pacing may cause electrical and mechanical dyssynchrony which lead finally to reduced left ventricular ejection fraction (LVEF). This deterioration of LVEF has been defined as pacemaker induced cardiomyopathy (PICM). The incidence of PICM was described by many studies and ranged between 10% to 26%. The predictors for PICM have not been well studied. These studies were limited by variation in follow-up period and definition of PICM. Objective to study the incidence and predictors of PICM in patients who underwent pacemaker implantation in Ain shams University hospital. Patients and Methods This retrospective study included 160 patients who underwent single or dual chamber pacemaker implantation in Ain shams university hospital between 2010 and 2017 with the mean period 4.7±2.0 years. Implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT) patients were excluded. Individuals who had baseline transthoracic echocardiography (TTE) with normal LVEF ≥ 50% before implantation were included. Results This study included 160 patients who had single or dual chamber pacemaker implantation between 2010 and 2017. 45% were males and 55% were females, mean age was 55.5 years. It showed that the incidence of PICM is 7.5%. Wider native QRS durations, particularly &amp;gt;140 ms (p &amp;lt; 0.001), wider pQRS duration &amp;gt;150 ms (p &amp;lt; 0.001), Low normal ejection fraction &amp;lt;56 % preimplantation (p = 0.023) and increased LVEDD&amp;gt;53 mm and LVESD&amp;gt;38 mm (p &amp;lt; 0.001) are predictors for the development of PICM. Female gender was independent predictor for PICM (p = 0.058). There was no association between burden of right ventricular pacing (p = 0.782) or pacing site (p = 0.876) with the risk of development of left ventricular dysfunction. Conclusion The incidence of right ventricular pacing-induced left ventricular dysfunction is not uncommon, with an observed incidence of 7.5% in the current study. Wider native and paced QRS durations, Low normal ejection fraction (&amp;lt; 56 %) pre-implantation and increased LVEDD /LVESD post implantation are the most important predictors for the development of PICM. List of abbreviations PM= pacemaker, RV= Right ventricle, PICM = pacemaker induced cardiomyopathy, TTE= transthoracic echocardiography, DM= Diabetes Mellitus, HTN= Hypertension, BMI= Body Mass index, pQRSd= Paced QRS duration, SWMA= segmental wall motion abnormality, AF= Atrial fibrillation, SSS= Sick sinus syndrome, CHB= Complete heart block, AVB= Atrioventricular block, LVEF = left ventricular ejection fraction, LVEDD= Left ventricular end diastolic diameter, LVESD= Left ventricular end systolic diameter, ms= milli second.

Successful Utilization of Poly-4-Hydroxybutyrate Mesh in High Risk, Complex Abdominal Wall Reconstructions with Photo-Microscopic Analysis.

Background: Biosynthetic resorbable mesh offers encouraging alternative for reinforcement in complex hernia repairs. This study evaluated outcomes of P4HB, absorbable polymer scaffold, in high-risk patients undergoing complex abdominal hernia repairs. Materials and Methods: This is a retrospective outcomes analysis of a prospectively kept database. Patient/wound characteristics, perioperative findings, short/mid-term outcomes of our cohort were analyzed. Endpoints included hernia recurrences, wound events and any complications. ACS NSQIP online risk calculator was used for each patient to obtain predicted outcomes as virtual matched control group. We also performed a full-thickness abdominal wall biopsy at 14-months post mesh implantation for histologic evaluation. Results: 28 patients with mean age 57 years and mean BMI 31 were analyzed. 21 patients (75%) had preexisting infections. 20 (71%) of patients had class I wounds per CDC classification at time of surgery. However, 19 of these 20 had wound or deep organ/space infections prior to surgery. Repair types included restoration of Linea Alba with retromuscular mesh placement in 23 patients (82%) with 22 of them requiring additional myofascial release. 5 patients (18%) had only mesh placement. Postoperatively, 11 patients (39%) had complications with zero hernia recurrence and zero mesh explantation at maximum of 42 months of follow up. Conclusion: P4HB can be successfully used in high-risk operative fields with no postoperative mesh explantation, despite serious complications such as infected hematomas. Histologic evaluation of the human tissue, 14-months post-implantation of P4HB confirms mesh presence with surrounding dense collagen scaffold formation and minimal inflammatory response.

BMP-treated human embryonic stem cells transcriptionally resemble amnion cells in the monkey embryo.

ABSTRACTHuman embryonic stem cells (hESCs) possess an immense potential to generate clinically relevant cell types and unveil mechanisms underlying early human development. However, using hESCs for discovery or translation requires accurately identifying differentiated cell types through comparison with their in vivo counterparts. Here, we set out to determine the identity of much debated BMP-treated hESCs by comparing their transcriptome to recently published single cell transcriptomic data from early human embryos ( Xiang et al., 2020). Our analyses reveal several discrepancies in the published human embryo dataset, including misclassification of putative amnion, intermediate and inner cell mass cells. These misclassifications primarily resulted from similarities in pseudogene expression, highlighting the need to carefully consider gene lists when making comparisons between cell types. In the absence of a relevant human dataset, we utilized the recently published single cell transcriptome of the early post implantation monkey embryo to discern the identity of BMP-treated hESCs. Our results suggest that BMP-treated hESCs are transcriptionally more similar to amnion cells than trophectoderm cells in the monkey embryo. Together with prior studies, this result indicates that hESCs possess a unique ability to form mature trophectoderm subtypes via an amnion-like transcriptional state.This article has an associated First Person interview with the first author of the paper.

Decentralized Cochlear Implant Programming Network Improves Access, Maintains Quality, and Engenders High Patient Satisfaction.

Cochlear implants have become a powerful tool in managing patients with moderate to profound sensorineural hearing loss and lack of benefit from hearing aids. Currently, less than 10% of people who would benefit from a CI receive the treatment. This lack of access is multi-factorial yet largely due in part to an inadequate referral system. The purpose of the current study was to evaluate speech outcomes and patient satisfaction for adult cochlear implant (CI) recipients in a single-surgeon, high volume CI center that uses a decentralized network (DCN) of private practice programming audiologists. Retrospective case series. Tertiary otology/neurotology practice. Adult CI recipients implanted between April 2017 and August 2019. Surgical/rehabilitative. Speech outcomes (AzBio quiet) were evaluated 6-months post implantation. Patients were surveyed to determine satisfaction with programming services, surgical services, and CI benefit. The senior author (A.J.) performed 223 CI operations: 136 (61%) were programmed at the CI center and 84 (38%) at outside audiology clinics through a DCN. The 6-month speech outcomes (AzBio, quiet) revealed similar scores regardless of where programming services were received; CI center: 25% pre-op versus 55% post-op; DCN: 24% pre-op versus 59% post-op. Additionally, patients reported high-levels of satisfaction with programming services, surgical services, and CI benefit. A decentralized network of well-trained private practice audiologists who identify CI candidates and program their devices after surgery 1) improves patient access to cochlear implantation, 2) maintains excellent speech outcomes, and 3) engenders high levels of patient satisfaction.

Analysis of Neural Interface When Using Modiolar Electrode Stimulation. Radiological Evaluation, Trans-Impedance Matrix Analysis and Effect on Listening Effort in Cochlear Implantation.

Background: The proximity of the electrode to the modiolar wall may be of interest to investigate the effect of pitch discrimination. This research establishes the relation between these factors and whether perimodiolar positions may provide benefits regarding improved electrode discrimination. Methods: A prospective randomized study including 24 post-lingual deaf adults was performed. A psychoacoustic study was done by using a psychoacoustic research platform. Radiological study, and a cone-beam computed tomography was used to assess post cochlear implantation electrodes’ position. Trans-impedance matrix (TIM) analysis was performed after cochlear implant insertion in all cases, and pupillometry test was also performed. Results: 12 patients received a slim perimodiolar electrode array, and 12 patients received a straight electrode array. Although all the patients showed similar speech test results after 12 months follow-up, those implanted with a perimodiolar electrode obtained better scores in electrode discrimination test and pupillometry test, and showed more homogenous TIM patterns. Conclusions: The better positioning of the electrode array seams to provide a better hearing resolution and less listening effort trans-impedance matrix seems to be a useful tool to analyze positioning of the perimodiolar array.

Significance of pre and post-implant MELD-XI score on survival in children undergoing VAD implantation

Derangements in liver and renal function often accompany end-stage heart failure. We sought to assess the utility of an objective risk assessment tool, the Model for End-stage Liver Disease eXcluding INR (MELD-XI), to identify pediatric patients at increased risk for adverse outcomes post-ventricular assist device (VAD) implantation. The Pedimacs database was queried for all pediatric patients who underwent VAD implantation from September 19, 2012 to December 31, 2019. Pre-implant and early (1-week) post-implant MELD-XI scores were used to stratify patients into low, intermediate and high score cohorts. Comparison of pre-implant characteristics and post-implant outcomes were conducted across groups. Multiphase parametric hazard modeling was utilized to identify independent predictors of post-implant mortality. A total of 742 patients had a calculable MELD-XI score pre-implant. When stratified by MELD-XI scores pre-implant, patients in the high MELD-XI score cohort (score >13.6) had inferior survival and increased bleeding, renal dysfunction and respiratory failure post-implant compared to intermediate and low score cohorts. Risk factors for mortality post-VAD implantation were: increasing MELD-XI scores (HR 1.1 per 1 unit rise), Pedimacs profile 1 (HR 1.6), congenital heart disease (HR 2.3) and being on a percutaneous VAD (HR 2.7). Importantly, MELD-XI score was a better predictor of post-VAD implant mortality than bilirubin or creatinine alone, neither of which were significant in the final model. Patients with increasing or continued high MELD-XI scores early post-implant had the worst survival. The MELD-XI is an easily calculated score that serves as a promising risk assessment tool in identifying children at risk for poor outcomes post VAD implantation.

P–174 Globulin-rich protein supplements improve blastulation efficiency in culture and promote implantation in vitro

Abstract Study question Can globulin-rich compared to albumin (HSA) supplements improve blastulation and support embryo development towards post implantation? Summary answer Yes, globulin supplements with clinical-grade quality increase blastulation efficiency by 20% (50% in older mothers) and support the transition of embryos towards post-implantation development. What is known already During embryonic development at the morula stage there is a metabolic transition towards glycolysis as demand from outsourced energy increases. Therefore as cleavage proceeds, the demand for nutrients in the embryo increases accordingly. With few exceptions, HSA from human plasma or recombinant origin has been the main an only protein supplement used in almost all IVF-procedures. Globulin rich supplements are available but their use is not widespread and little is known about their efficiency in post-implantation development. Study design, size, duration We have cultured more than 600 mouse embryos in continuous media containing a protein supplement#1 (PS#1), from 1-cell up to blastocyst stage. At blastocyst stage embryos were replaced into fresh media containing protein supplement#2 (PS#2). The embryos were allowed to hatch naturally and then transferred into a proprietary matrix for further development and implantation for an additional 48h. Participants/materials, setting, methods: The blastulation rate, measured for HSA-supplemented embryo cohort was compared with embryos cultured in PS#1. Hatching efficiency was reported for embryos cultured in transfer media including PS#2. Once embedded in the matrix, advanced label-free imaging techniques and custom algorithms to measure matrix implantation strength were used. Key molecular markers (i.e. OCT4, CDX2) for correct post-implantation lineage patterning were documented by conventional 3D confocal immunofluorescence imaging. Main results and the role of chance Embryos supplemented with PS#1 reached blastocyst with overall 21% higher efficiency than embryos supplemented by HSA. When separated by age cohorts, embryos obtained from older females (ex-colony breeders, &amp;gt;14 weeks old) reached blastocyst stage with 55% higher efficiency than the same type of embryos cultured in the presence of HSA. Embryos obtained from females at optimal reproductive age reached blastocyst stage 10% more efficiently under PS#1 supplementation than with HSA. Hatching efficiency was 45% higher for embryos cultured with PS#2 than embryos supplemented with HSA. For every variable tested (e.g.% of arrested or degenerated embryos) or condition implemented (e.g. mouse basal media, human basal media from different brands, etc.) PS#1 and PS#2 outperformed, without exception, the supplementation with HSA. When embedded in the implantation matrix, the embryos cultured with PS#1 (cleavage) and transferred to PS#2 at blastocyst stage showed a remarkable implantation ability as measured by trophoblast outgrowth and matrix deformations. The embryos in PS#2 medium exerted stronger force into the matrix and also survived longer times than the embryos in HSA. PS#2 supported the transition of blastocyst towards post-implantation stages of development showing the correct lineage patterning of embryonic and extraembryonic molecular markers, including Oct4, CDx2, EOMES or GATA4. Limitations, reasons for caution This is a study based on an animal model. These observations need to be confirmed by ongoing experiments with human embryos. Wider implications of the findings: This work constitutes a proof-of-concept for the use of globulin-rich supplements as higher performance substitute of albumin in the culture of IVF embryos, both as (i) a standard protein source for culture media and (ii) as a supplement for transfer media to capacitate the embryo for implantation. Trial registration number Not applicable

P–572 Purifying selection for aneuploidy cells in mosaicism embryo at post-implantation stage

Abstract Study question Why low ratio mosaicism embryos develop to normal karyotype babies? Summary answer Our in vitro implantation assay clarified purifying selection for aneuploid cells in post implantation embryos. What is known already There are some reports about healthy live birth after transfer of mosaic embryos, which was reported for the first time from Italy in 2015. It is also reported that the abnormal cell is screened with the mouse in the embryo development, and only a normal cell contributes to the development. But it has not been examined in human. Study design, size, duration To clarify the change of aneuploid cells and mitochondrial activity in human embryo, we biopsied several parts from one blastocyst and examined karyotype. After in vitro implantation assay for biopsied embryos, we compared the karyotype of biopsy sample with that of cultured cell mass. Participants/materials, setting, methods Under the ethical review of Yokohama City University and informed consent with patients, we collected human surplus blastocysts those are donated after successful clinical treatment or discarded because of poor development grade. We biopsied multiple parts from one blastocyst and cultured the biopsied embryos, and extracted whole DNA from the biopsy samples and cultured embryos. Karyotyping by next generation sequencing were performed. Main results and the role of chance We analyzed 34 samples from 11 embryos, including 25 biopsy sample from 11 embryos and 9 cell mass from 7 cultured embryos. In the karyotype tracking results, even though biopsy sample analysis before the culture were uniformed aneuploid or chromosome mosaic, the developing embryo cell mass had normal karyotype. In one embryo as an example, among the three biopsied extra trophectoderm samples from that, two of them were mosaic, and one of them had uniformed chromosome 21 trisomy and chromosome 16 mosaic monosomy. But the embryo formed multiple cell mass in implantation assay. We examined karyotype of three cell mass, and the result from all were normal karyotype. We suggested that the chromosome aberration cells were screened in the human embryo development, and when the function was not carried out the embryo stopped the development. Limitations, reasons for caution Because of small number of samples available, we need more samples for a more accurate evaluation. Furthermore, we cannot evaluate the absolute mechanism that cells with chromosome aberration decreases. Wider implications of the findings: Conventional PGT-A techniques are based on uniformed embryos developing hypothesized past time. As showed in some clinical reports, PGT-A can reduce of spontaneous abortion and chance of embryo transfer. Thinking about aneuploid cell purifying system in embryo development, effectiveness of PGT-A should be more questionable for infertility treatment. Trial registration number A200326004

P–211 Double warming and double vitrification for euploid embryos does not affect implantation nor ongoing pregnancy rate

Abstract Study question Does exposure of embryos to double vitrification and double warming affect the chances of ongoing pregnancy for patients undergoing PGT-A and transfer euploid embryos? Summary answer Our analysis shows that there is no statistically significant difference in implantation or ongoing pregnancy rate between single or double vitrification/warming cycles. What is known already The use of PGT-A is increasing in the last years and progressively more patients opting in for this, in order to reduce time to pregnancy. Implantation failures prior to genetic testing or the incidence of no-result embryos post PGT-A are some of the scenarios that expose the embryos to multiple rounds of vitrification/warming cycles. The exact effect that such exposure has on embryos is still to be investigated and confirmed as to whether it affects the outcome (i.e. implantation/ongoing pregnancy rate) or the future health of the child. Study design, size, duration Our analysis is a retrospective observation study of data collected from 151 consecutive frozen euploid embryo transfers (FET). These were performed at a single centre between January-December 2020. Two groups were created for this study. The first group includes euploid embryos that were transferred post being exposed to single vitrification/warming (n = 126). In the second group euploid embryos were exposed twice to vitrification/warming (n = 25). Statistical analysis using chi-square test and statistical significance was calculated when p ≤ 0.05. Participants/materials, setting, methods Blastocysts from 151 patients were split into two groups based on the number of vitrification/warming cycles that they underwent prior to FET. The first group includes embryos that were subjected to trophectoderm biopsy and were then vitrified (n = 126). The second group includes embryos that were initially vitrified without undergoing PGT-A analysis. Following implantation failures, their remaining embryos were warmed, biopsied and re-vitrified. Post PGT-A analysis euploid embryos were then re-warmed and transferred (n = 25). Main results and the role of chance For the first group (A), 450 blastocysts (day 5–7) were subjected to trophectoderm biopsy, where 5-cells taken, and embryos were then vitrified. Post PGT-A analysis 260 euploid embryos identified. From them 126 embryos transferred in frozen replacement cycles, where the mean embryo age for the group was 36.1±4.2. The grade of embryos transferred were of 4BC or better based on Gardner’s grading system. The implantation and ongoing pregnancy rate for this group was 62%. For the second group (B), 101 blastocysts (day 5–7) warmed, in order to undergo trophectoderm biopsy and were then re-vitrified. Post PGT-A analysis 49 euploid embryos identified. From them, 25 embryos transferred in frozen replacement cycles, where the mean maternal age for the group was 35.05±5.2. The grade of embryos transferred were of similar quality to group A. The implantation and ongoing pregnancy rate for this group was 64%. Statistical analysis confirmed that there is no statistical difference between the groups (p = 0.74). In addition, 60% of patients (n = 5) who had double vitrification, double biopsy and double warming have ongoing pregnancy. In conclusion, for transferrable quality euploid blastocysts, double vitrification has comparable reproductive outcomes as in single vitrification, thereby supporting the efficacy of double vitrification/warming when necessary. Limitations, reasons for caution This study uses a small sample size of patients. The data are observational and were retrospectively analysed so unknown confounders could not be assessed. The addition of more cycles and further multivariate analysis, including the child’s health is essential for confirmation of the findings. However, initial results are very reassuring. Wider implications of the findings: Our study has implications for clinical practice and patient counselling. Especially in patients that they choose to undergo PGT-A with pre-vitrified embryos post implantation failures with non PGT-A tested embryos. Trial registration number N/A