Association between pulmonary artery pulsatility and mortality after implantation of left ventricular assist device.

AIMS: Right ventricular failure after left ventricular assist device (LVAD) implantation is a major concern that remains challenging to predict. We sought to investigate the relationship between preoperative pulmonary artery pulsatility index (PAPi) and mortality after LVAD implantation. METHODS AND RESULTS: A retrospective analysis of the ASSIST-ICD multicentre registry allowed the assessment of PAPi before LVAD according to the formula [(systolic pulmonary artery pressure - diastolic pulmonary artery pressure)/central venous pressure]. The primary endpoint was survival at 3 months, according to the threshold value of PAPi determined by the receiver operating characteristic (ROC) curve. A multivariate analysis including demographic, echographic, haemodynamic, and biological variables was performed to identify predictive factors for 2 year mortality. One hundred seventeen patients were included from 2007 to 2021. The mean age was 58.45 years (±13.16), with 15.4% of women (sex ratio 5.5). A total of 53.4% were implanted as bridge to transplant and 43.1% as destination therapy. Post-operative right ventricular failure was observed in 57 patients (48.7%), with no significant difference between survivors and non-survivors at 1 month (odds ratio 1.59, P = 0.30). The median PAPi for the whole study population was 2.83 [interquartile range 1.63-4.69]. The threshold value of PAPi determined by the ROC curve was 2.84. Patients with PAPi ≥ 2.84 had a higher survival rate at 3 months [PAPi < 2.84: 58.1% [46.3-72.8%] vs. PAPi ≥ 2.84: 89.1% [81.1-97.7%], hazard ratio (HR) 0.08 [0.02-0.28], P < 0.01], with no significant difference after 3 months (HR 0.67 [0.17-2.67], P = 0.57). Other predictors of 2 year mortality were systemic hypertension (HR 4.22 [1.49-11.97], P < 0.01) and diabetes mellitus (HR 4.90 [1.83-13.14], P < 0.01). LVAD implantation as bridge to transplant (HR 0.18 [0.04-0.74], P = 0.02) and heart transplantation (HR 0.02 [0.00-0.18], P < 0.01) were associated with a higher survival rate at 2 years. CONCLUSIONS: Preoperative PAPi < 2.84 was associated with a higher risk of early mortality after LVAD implantation without impacting 2 year outcomes among survivors.

Doppler echocardiography for surveillance of acute cardiac allograft rejection: a 28-year single-center experience.

Background: Endomyocardial biopsies (EMB) are recommended for the detection of acute cardiac rejection (ACR) despite limited sensitivity. We report the long-term post-transplant results of Doppler echocardiography as a noninvasive alternative of routine EMB. Methods: Two cohorts of heart transplantation (HT) recipients were chronologically defined as follows: the Dual Monitoring Cohort (DMC) from January 1990 to December 1997 included patients who underwent routine EMB and Doppler echocardiography within 24 hours for ACR surveillance; and the "Echo-First Cohort" (EFC), including patients transplanted from January 1998 to December 2018 with Doppler echocardiography as first-line approach for ACR surveillance. Echocardiographic measurements of interest were collected: early diastolic (E) wave peak velocity; pressure half time (PHT) and isovolumetric relaxation time (IVRT). Post-transplant outcomes were reviewed and the Kaplan-Meier approach was used for survival estimates. Inter-operator variability for ultrasound measurements was investigated. Data were collected from medical records from January 2019 to December 2020. Results: A total of 228 patients were included, 99 patients in the DMC and 129 in the EFC. Overall, 5-, 10- and 15-year survival rates were 65.4%, 55.5% and 44.1% respectively, without any significant difference between the two cohorts (log rank test, P=0.71). Echocardiography variables and EMB findings were associated with a mean area under the receiver operating characteristic curve (AUC-ROC) of 0.73 [95% confidence interval (CI): 0.54-0.91], 0.74 (95% CI: 0.54-0.94) and 0.75 (95% CI: 0.57-0.94) respectively for E wave, PHT and IVRT. IVRT and PHT were significantly decreased, and E wave significantly increased, in case of histologically proven ACR. Inter-operator variability was not significant for E wave and IVRT measurements (P=0.13 and 0.30 respectively). Conclusions: Doppler echocardiography as a first-line method for surveillance of ACR did not impair long-term results after HT. These findings suggest that this non-invasive approach might be a reasonable alternative to systematic EMB, limiting risk and improving the quality of life.

Early and Midterm Outcomes of Endovascular Aortic Arch Repair Using In Situ Laser Fenestration.

INTRODUCTION: The aim of this study is to present single-center outcomes in patients treated with in situ laser fenestration thoracic endovascular aortic repair (LFTEVAR) for various aortic arch pathologies and assess the impact of increasing experience. METHODS: The STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement was followed. A retrospective analysis of prospectively collected single aortic center data was conducted, including baseline information and peri- and post-operative outcomes of consecutive patients managed with LFTEVAR for aortic arch pathologies. Patients were enrolled from April 1, 2017 to January 31, 2023. The cohort was dichotomized to compare early (2017-2019) and late experience (2020-2023). Primary outcomes were peri-operative mortality and cerebrovascular morbidity. RESULTS: Thirty patients were included (63.3% males, mean age 69.8±9.6 years); 21.4% presented with aortic ruptures. Aortic aneurysm involving the aortic arch was the most frequent pathology (53.3%). Forty target vessels (TVs) were revascularized, including 19 left subclavian arteries (47.5%) and 17 left common carotid arteries (42.5%). Double fenestrations were performed in 10 patients. The proximal landing zone was Ishimaru zone 0 in 5 patients (16.7%) and zone 1 in 13 patients (43.3%). Technical success was 93%. No spinal cord ischemia was recorded, and 3 patients (10%) suffered a post-operative stroke, of which 1 was major (3.3%). The median follow-up was 12 months (range=1-48 months). Thirty-day and follow-up mortality rates were 13.5% and 15.3%, respectively. Target vessel instability was 10%, of which 3.8% required reintervention. There was no statistically significant difference in outcomes between the early and late experience groups. CONCLUSIONS: Laser fenestration thoracic endovascular aortic repair of the aortic arch performed in experienced aortic centers is associated with low early mortality and stroke rates. It is a safe and effective therapeutic option in patients considered unfit for open repair. CLINICAL IMPACT: Custom-made devices for arch pathologies requiring urgent repair are not an option because of manufacturing delays. Off-the-shelf devices with single branch arch prostheses, and outside IFU techniques such as parallel-grafts and surgeon-modified endografts have been proposed in this setting. Another off-the-shelf alternative is in situ laser fenestration thoracic endovascular repair (LFTEVAR), which addresses many limitations of the other off-the-shelf options. Our study reports the outcomes of 30 patients treated with LFTEVAR, showing that it is a viable therapeutic option in patients considered unfit for open repair acknowledging that sufficient experience with complex endovascular aortic repair is mandatory to achieve acceptable outcomes in these high-risk patients with challenging aortic anatomies.

Heart graft preservation technics and limits: an update and perspectives.

Heart transplantation, the gold standard treatment for end-stage heart failure, is limited by heart graft shortage, justifying expansion of the donor pool. Currently, static cold storage (SCS) of hearts from donations after brainstem death remains the standard practice, but it is usually limited to 240 min. Prolonged cold ischemia and ischemia-reperfusion injury (IRI) have been recognized as major causes of post-transplant graft failure. Continuous ex situ perfusion is a new approach for donor organ management to expand the donor pool and/or increase the utilization rate. Continuous ex situ machine perfusion (MP) can satisfy the metabolic needs of the myocardium, minimizing irreversible ischemic cell damage and cell death. Several hypothermic or normothermic MP methods have been developed and studied, particularly in the preclinical setting, but whether MP is superior to SCS remains controversial. Other approaches seem to be interesting for extending the pool of heart graft donors, such as blocking the paths of apoptosis and necrosis, extracellular vesicle therapy, or donor heart-specific gene therapy. In this systematic review, we summarize the mechanisms involved in IRI during heart transplantation and existing targeting therapies. We also critically evaluate all available data on continuous ex situ perfusion devices for adult donor hearts, highlighting its therapeutic potential and current limitations and shortcomings.

Impact of the COVID-19 Pandemic on Complex Aortic Aneurysm Surgery.

INTRODUCTION: This study aimed to evaluate the impact of COVID on total case load and peri-operative outcomes in patients undergoing open surgical repair (OSR) and endovascular repair (ER) of complex aortic aneurysms (cAAs). METHODS: A single-center retrospective analysis of prospective data of patients managed with elective cAA ER or OSR from January 2018 to December 2021 was conducted. A comparative analysis on the impact of the COVID-19 pandemic on the case volume and on the 30-day outcomes was assessed using time periods, before (2018-2019) and during the pandemic (2020-2021). RESULTS: During the 4-year study period, 255 patients with cAA were managed with ER and 576 with OSR. The pandemic did not reduce the cAA ER volume (p=0.12), but a statistically significant reduction in OSR case load was recorded (p=0.04). Following OSR, hospital length of stay (11.1 vs 10.3 days), and early mortality (6.94% vs 4.63%), were similar before and during the pandemic. In the ER cohort, baseline characteristics, early mortality (3.6% vs 4.1%, p=0.976), and morbidity (10% vs 14%, p=0.44), were comparable during the 2 periods. For ER cases, the hospital and intensive care unit (ICU) stay both decreased significantly (8±8-6±7 days, p<0.001 and 2±4 vs 1±6 days p=0.01, respectively) during the pandemic. CONCLUSION: Resource pressures drove modifications in clinical practice to reduce the length of hospitalization, without compromising the clinical outcomes, in patients undergoing ER of cAA. This modification was not effective in patients undergoing OSR that resulted in a significant decrease of this activity. CLINICAL IMPACT: The pandemic did not reduce complex endovascular repair (ER) volume (p=0.12) while a significant reduction in open surgical repair (OSR) case load was recorded (p=0.04). For the endovascular cohort, early mortality (p=0.976) and morbidity (p=0.44) remained stable, while the hospital and intensive care unit (ICU) stay decreased (p<0.001 and p=0.01, respectively) during the pandemic.

Early Outcomes on Triple-Branch Arch Device With Retrograde Left Common Carotid Branch: A Case Series.

INTRODUCTION: Endovascular aortic arch repair using multibranch devices has been applied in patients considered at high risk for open repair. The aim of this case series was to report the early outcomes in patients managed with a new design 3 branch arch custom-made device, including a retrograde left common carotid artery (LCCA) branch. METHODS: The Preferred Reporting Of CaSe Series in Surgery (PROCESS) guidelines were followed. All consecutive patients undergoing endovascular repair of an aortic arch lesion with a custom-made triple-branch device, including a retrograde LCCA branch (Cook Medical, Bloomington, IN, USA), between October 27, 2022, and February 28, 2023, were included. The presence of an arch aneurysm (degenerative or post-dissection) with diameter ≥55 mm and high risk for a conventional open repair set the indication for treatment. The primary outcomes were technical success and mortality at 30 days. Early morbidity and reinterventions were considered as secondary outcomes. RESULTS: Eight elective patients (87.5% men, mean age 72.3±27.0 years) were included. Five of them (62.5%) had undergone a previous ascending aorta repair of an acute type A aortic dissection. All patients were asymptomatic, except one, with left recurrent laryngeal nerve compression. The mean maximum aortic diameter was 70.4±21.0 mm. Percutaneous femoral and axillary access was used in all cases except three in which a cut down for right carotid access was performed. Technical success was 100%. Femoral access to the LCCA and implantation of the bridging stent was performed without technical challenges. No death nor cerebrovascular event was recorded during the 30 day follow-up. Five patients (62.5%) presented major complications, 3 related to access needing reintervention and the remaining related to congestive heart failure (CHF), which were managed successfully with medical treatment. Follow-up (range 1-4 month) was uneventful, except for one patient who presented a secondary type Ia endoleak. CONCLUSIONS: According to our early experience, the presence of a retrograde branch facilitated the revascularization of the LCCA through femoral access, decreasing the risk of cerebrovascular morbidity. Further analyses with longer follow-up are needed to evaluate the safety and efficacy of the device. CLINICAL IMPACT: Data arising mainly from the retrograde branch for the revascularization of the LSA are encouraging from a variety of devices. The premiminary experience with a triple-branched arch device, with a retrograde branche for the LSA but also for the LCCA, was associated with no 30 day mortality and 100% technical success.The device's design allowed swift catheterization and completion of the LCCA revascularization using femoral access exclusively.

Diuretic dose is a strong prognostic factor in ambulatory patients awaiting heart transplantation.

AIMS: The prognostic value of 'high dose' loop diuretics in advanced heart failure outpatients is unclear. We aimed to assess the prognosis associated with loop diuretic dose in ambulatory patients awaiting heart transplantation (HT). METHODS AND RESULTS: All ambulatory patients (n = 700, median age 55 years and 70% men) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 were included. Patients were divided into 'low dose', 'intermediate dose', and 'high dose' loop diuretics corresponding to furosemide equivalent doses of ≤40, 40-250, and >250 mg, respectively. The primary outcome was a combined criterion of waitlist death and urgent HT. N-terminal pro-B-type natriuretic peptide, creatinine levels, pulmonary capillary wedge pressure, and pulmonary pressures gradually increased with higher diuretic dose. At 12 months, the risk of waitlist death/urgent HT was 7.4%, 19.2%, and 25.6% (P = 0.001) for 'low dose', 'intermediate dose', and 'high dose' patients, respectively. When adjusting for confounders, including natriuretic peptides, hepatic, and renal function, the 'high dose' group was associated with increased waitlist mortality or urgent HT [adjusted hazard ratio (HR) 2.23, 1.33 to 3.73; P = 0.002] and a six-fold higher risk of waitlist death (adjusted HR 6.18, 2.16 to 17.72; P < 0.001) when compared with the 'low dose' group. 'Intermediate doses' were not significantly associated with these two outcomes in adjusted models (P > 0.05). CONCLUSIONS: A 'high dose' of loop diuretics is strongly associated with residual congestion and is a predictor of outcome in patients awaiting HT despite adjustment for classical cardiorenal risk factors. This routine variable may be helpful for risk stratification of pre-HT patients.

Veno-arterial extracorporeal membrane oxygenation for circulatory failure in COVID-19 patients: insights from the ECMOSARS registry.

OBJECTIVES: The clinical profile and outcomes of patients with Coronavirus Disease 2019 (COVID-19) who require veno-arterial extracorporeal membrane oxygenation (VA-ECMO) or veno-arterial-venous extracorporeal membrane oxygenation (VAV-ECMO) are poorly understood. We aimed to describe the characteristics and outcomes of these patients and to identify predictors of both favourable and unfavourable outcomes. METHODS: ECMOSARS is a multicentre, prospective, nationwide French registry enrolling patients who require veno-venous extracorporeal membrane oxygenation (ECMO)/VA-ECMO in the context of COVID-19 infection (652 patients at 41 centres). We focused on 47 patients supported with VA- or VAV-ECMO for refractory cardiogenic shock. RESULTS: The median age was 49. Fourteen percent of patients had a prior diagnosis of heart failure. The most common aetiologies of cardiogenic shock were acute pulmonary embolism (30%), myocarditis (28%) and acute coronary syndrome (4%). Extracorporeal cardiopulmonary resuscitation (E-CPR) occurred in 38%. In-hospital survival was 28% in the whole cohort, and 43% when E-CPR patients were excluded. ECMO cannulation was associated with significant improvements in pH and FiO2 on day 1, but non-survivors showed significantly more severe acidosis and higher FiO2 than survivors at this point (P = 0.030 and P = 0.006). Other factors associated with death were greater age (P = 0.02), higher body mass index (P = 0.03), E-CPR (P = 0.001), non-myocarditis aetiology (P = 0.02), higher serum lactates (P = 0.004), epinephrine (but not noradrenaline) use before initiation of ECMO (P = 0.003), haemorrhagic complications (P = 0.001), greater transfusion requirements (P = 0.001) and more severe Survival after Veno-Arterial ECMO (SAVE) and Sonographic Assessment of Intravascular Fluid Estimate (SAFE) scores (P = 0.01 and P = 0.03). CONCLUSIONS: We report the largest focused analysis of VA- and VAV-ECMO recipients in COVID-19. Although relatively rare, the need for temporary mechanical circulatory support in these patients is associated with poor prognosis. However, VA-ECMO remains a viable solution to rescue carefully selected patients. We identified factors associated with poor prognosis and suggest that E-CPR is not a reasonable indication for VA-ECMO in this population.

Pulmonary hypertension without heart failure causes cardiorenal syndrome in a porcine model.

Cardiorenal syndromes type 1 and 2 are complex disorders in which cardiac dysfunction leads to kidney dysfunction. However, the mechanisms remain incompletely explained, during pulmonary hypertension in particular. The objective of this study is to develop an original preclinical model of cardiorenal syndrome secondary to a pulmonary hypertension in piglets. Twelve 2-month-old Large White piglets were randomized in two groups: (1) induction of pulmonary hypertension by ligation of the left pulmonary artery and iterative embolizations of the right lower pulmonary artery, or (2) Sham interventions. We evaluated the cardiac function using right heart catheterization, echocardiography and measurement of biochemistry markers). Kidney was characterized using laboratory blood and urine tests, histological evaluation, immunostainings for renal damage and repair, and a longitudinal weekly assessment of the glomerular filtration rate using creatinine-based estimation and intravenous injection of an exogenous tracer on one piglet. At the end of the protocol (6 weeks), the mean pulmonary artery pressure (32 ± 10 vs. 13 ± 2 mmHg; p = 0.001), pulmonary vascular resistance (9.3 ± 4.7 vs. 2.5 ± 0.4 WU; p = 0.004) and central venous pressure were significantly higher in the pulmonary hypertension group while the cardiac index was not different. Piglets with pulmonary hypertension had higher troponin I. We found significant tubular damage and an increase in albuminuria in the pulmonary hypertension group and negative correlation between pulmonary hypertension and renal function. We report here the first porcine model of cardiorenal syndrome secondary to pulmonary hypertension.

Systematic Review on In Situ Laser Fenestrated Repair for the Endovascular Management of Aortic Arch Pathologies.

BACKGROUND: In situ laser-fenestrated thoracic aortic endovascular repair (FTEVAR) has emerged as a valuable alternative for aortic arch management. This review assessed the early and follow-up outcomes of in situ laser-FTEVAR in aortic arch pathologies. METHODS: The PRISMA statement was followed. The English literature was searched, via Ovid, until 15 October 2022. Observational studies, published after 2000, reporting on early and follow-up outcomes for the in situ laser-FTEVAR were eligible. The Newcastle-Ottawa Scale was used to assess the risk of bias. Primary outcomes were the technical success, stroke, and mortality at 30-days, and the secondary were the mortality and reintervention during follow-up. RESULTS: Six retrospective studies from 591 and 247 patients were included. Fifty-nine (23.9%) patients were managed for aortic arch aneurysms and 146 (59.1%) for dissections; 22.6% of them for type A. Technical success was at 98% (range 90-100%). Eight patients died (3.2%) and 11 cases presented any type of stroke (4.5%) during the 30-day follow-up. The mean follow-up was 15 months (1-40 months). Ten deaths were reported (4.2%); one was aortic-related (10%). Thirteen re-interventions (6.0%) were performed. CONCLUSIONS: In situ laser-FTEVAR for aortic arch repair may be performed with high technical success and low 30-day and midterm follow-up mortality, stroke, and re-intervention rates when applied in well selected patients and performed by experienced teams.

Imaging the vasculature of a beating heart by dynamic speckle: the challenge of a quasiperiodic motion.

The spatial and temporal evolution of the field backscattered by a beating heart while illuminated with a coherent light reveals its macro- and microvascularization in real time. To perform these vascularization images, we use a recently published method of laser speckle imaging, based on the selective detection of spatially depolarized speckle field that is mainly generated by multiple scattering. We consider the calculation of the speckle contrast, by a spatial or temporal estimation. We show that the signal-to-noise ratio of the observed vascular structure can be noticeably increased by a postprocessing method implying the calculation of a motion field that allows the selection of similar frames extracted from different heartbeat periods. This later optimization reveals vascular microstructures with a spatial resolution of the order of 100 µ m .

Metabolomic profiling of cardiac allografts after controlled circulatory death.

BACKGROUND: Assessment of myocardial viability during ex situ heart perfusion (ESHP) is based on the measurement of lactate concentrations. As this provides with limited information, we sought to investigate the metabolic signature associated with donation after circulatory death (DCD) and the impact of ESHP on the myocardial metabolome. METHODS: Porcine hearts were retrieved either after warm ischemia (DCD group, N = 6); after brain-stem death (BSD group, N = 6); or without DCD nor BSD (Control group, N = 6). Hearts were perfused using normothermic oxygenated blood for 240 minutes. Plasma and myocardial samples were collected respectively every 30 and 60 minutes, and analyzed by an untargeted metabolomic approach using liquid chromatography coupled to high-resolution mass spectrometry. RESULTS: Median duration of warm ischemia was 23 minutes [19-29] in DCD animals. Lactate level within myocardial biopsies was not significantly different between groups at T0 (p = 0.281), and remained stable over the 4-hour period of ESHP. More than 300 metabolites were detected in plasma and heart biopsy samples. Compared to BSD animals, metabolomics changes involving energy and nucleotide metabolisms were observed in plasma samples of DCD animals before initiation of ESHP, whereas 2 metabolites (inosine monophosphate and methylbutyrate) exhibited concentration changes in biopsy samples. Normalization of DCD metabolic profile was remarkable after 4 hours of ESHP. CONCLUSION: A specific metabolic profile was observed in DCD hearts, mainly characterized by an increased nucleotide catabolism. DCD and BSD metabolomes proved normalized during ESHP. Complementary investigations are needed to correlate these findings to cardiac performances.

Single-cell mass cytometry on peripheral cells in Myasthenia Gravis identifies dysregulation of innate immune cells.

Myasthenia Gravis (MG) is a neurological autoimmune disease characterized by disabling muscle weaknesses due to anti-acetylcholine receptor (AChR) autoantibodies. To gain insight into immune dysregulation underlying early-onset AChR+ MG, we performed an in-depth analysis of peripheral mononuclear blood cells (PBMCs) using mass cytometry. PBMCs from 24 AChR+ MG patients without thymoma and 16 controls were stained with a panel of 37 antibodies. Using both unsupervised and supervised approaches, we observed a decrease in monocytes, for all subpopulations: classical, intermediate, and non-classical monocytes. In contrast, an increase in innate lymphoid cells 2 (ILC2s) and CD27- γδ T cells was observed. We further investigated the dysregulations affecting monocytes and γδ T cells in MG. We analyzed CD27- γδ T cells in PBMCs and thymic cells from AChR+ MG patients. We detected the increase in CD27- γδ T cells in thymic cells of MG patients suggesting that the inflammatory thymic environment might affect γδ T cell differentiation. To better understand changes that might affect monocytes, we analyzed RNA sequencing data from CD14+ PBMCs and showed a global decrease activity of monocytes in MG patients. Next, by flow cytometry, we especially confirmed the decrease affecting non-classical monocytes. In MG, as for other B-cell mediated autoimmune diseases, dysregulations are well known for adaptive immune cells, such as B and T cells. Here, using single-cell mass cytometry, we unraveled unexpected dysregulations for innate immune cells. If these cells are known to be crucial for host defense, our results demonstrated that they could also be involved in autoimmunity.

In Situ Fenestrated Thoracic Endovascular Repair Using the Upstream Peripheral Go BackTM Re-Entry Catheter.

PURPOSE: The aim is to present a case of in situ fenestrated thoracic endovascular repair, using a re-entry peripheral catheter, needing urgent repair due to recurrent episodes of hemoptysis because of an aorto-bronchial fistula after previous thoracic endovascular aortic repair (TEVAR). TECHNIQUE: A 74-year-old male with a previous TEVAR presented with hemoptysis, fever, and cachexia. An aorto-bronchial fistula and type Ia endoleak were depicted on computed tomography angiography (CTA). Due to the patient's frail general condition, a proximal TEVAR extension was planned, prior to thoracotomy for debridement, and long-term antibiotics. An in situ fenestrated TEVAR was performed to provide proximal sealing and revascularize the left common carotid and subclavian arteries. For fenestration creation, an Upstream Peripheral Go Back catheter (Bentley, Hechingen, Germany) was used. The Go Back catheter has been approved as a re-entry tool for complex peripheral arterial revascularization. In this case, both fenestrations were successfully created. Proximal seal and target vessel patency were confirmed on CTA. Thoracotomy confirmed aortic exclusion. A wedge lobectomy was performed in combination with pediculated omentectomy to exclude the exposed endograft. CONCLUSION: In urgent cases, where custom-made thoracic devices are unavailable, in situ fenestrations with the Go Back catheter are an alternative to laser fenestrations. CLINICAL IMPACT: Fenestrations are often required in acute TEVAR to achieve a proximal seal in the arch. In situ fenestrations with the Go Back catheter are an alternative to laser fenestrations and PMEGs in this setting.

Central Role of Macrophages and Nucleic Acid Release in Myasthenia Gravis Thymus.

OBJECTIVE: Myasthenia gravis (MG) is a neuromuscular disease mediated by antibodies against the acetylcholine receptor (AChR). The thymus plays a primary role in AChR-MG and is characterized by a type I interferon (IFN) signature linked to IFN-ß. We investigated if AChR-MG was characterized by an IFN-I signature in the blood, and further investigated the chronic thymic IFN-I signature. METHODS: Serum levels of IFN-ß and IFN-α subtypes, and mRNA expression for IFN-I subtypes and IFN-stimulated genes in peripheral mononuclear blood cells (PBMCs) were analyzed. The contribution of endogenous nucleic acids in thymic expression of IFN-I subtypes was investigated in human thymic epithelial cell cultures and the mouse thymus. By immunohistochemistry, thymic CD68+ and CD163+ macrophages were analyzed in AChR-MG. To investigate the impact of a decrease in thymic macrophages, mice were treated with an anti-CSF1R antibody. RESULTS: No IFN-I signature was observed in the periphery emphasizing that the IFN-I signature is restricted to the MG thymus. Molecules mimicking endogenous dsDNA signalization (Poly(dA:dT) and 2'3'-cGAMP), or dexamethasone-induced necrotic thymocytes increased IFN-ß and α-AChR expression by thymic epithelial cells, and in the mouse thymus. A significant decrease in thymic macrophages was demonstrated in AChR-MG. In mice, a decrease in thymic macrophages led to an increase of necrotic thymocytes associated with IFN-ß and α-AChR expression. INTERPRETATION: These results suggest that the decrease of thymic macrophages in AChR-MG impairs the elimination of apoptotic thymocytes favoring the release of endogenous nucleic acids from necrotic thymocytes. In this inflammatory context, thymic epithelial cells may overexpress IFN-ß, which specifically induces α-AChR, resulting in self-sensitization and thymic changes leading to AChR-MG. ANN NEUROL 2023;93:643-654.

A Review: Single and MultiBranch Devices for the Treatment of Aortic Arch Pathologies with Proximal Sealing in Ishimaru Zone 0.

Recently published experience has shown that endovascular management of the aortic arch, including sealing in the proximal zones, can be a viable option for patients considered unfit for conventional open repair. Endograft designs vary and include single or multibranch devices, with or without the addition of surgical debranching. Initial reports show that both techniques can be performed with high technical success and acceptable perioperative morbidity and mortality rates in high volume centers. Single branch devices, available off-the-shelf, may provide a treatment option for emergent presentations where patients cannot wait for the design and manufacture of a customized endograft. Double or triple branched endografts are now increasingly implanted in high-volume aortic centers. The purpose of this review is to describe the single and multibranched endovascular devices currently available for aortic arch repair, their associated published outcomes, and to discuss their relative advantages and disadvantages.

Functional Assessment of the Donor Heart During Ex Situ Perfusion: Insights from Pressure-Volume Loops and Surface Echocardiography.

Heart transplantation remains the gold standard treatment for advanced heart failure. However, the current critical organ shortage has resulted in the allocation of a growing number of donor hearts with extended criteria. These marginal grafts are associated with a high risk of primary graft failure and may benefit from ex situ perfusion before transplant. This technology allows for extended organ preservation using warm oxygenated blood perfusion with continuous metabolic monitoring. The only NESP device currently available for clinical practice perfuses the organ in an unloaded non-working state, which does not allow for functional assessment of the beating heart. We therefore developed an original platform of NESP in working mode conditions with adjustment of left ventricular preload and afterload. This protocol was applied in porcine hearts. Ex situ functional assessment of the heart was achieved with intracardiac conductance catheterization and surface echocardiography. Along with a description of the experimental protocol, we herein report the main results, as well as pearls and pitfalls associated with the acquisition of pressure-volume loops and myocardial power during NESP. Correlations between hemodynamic findings and ultrasound variables are of major interest, especially for further rehabilitation of donor hearts before transplantation. This protocol aims to improve the assessment of donor hearts to both increase the donor pool and reduce the incidence of primary graft failure.

Prognosis value of Forrester's classification in advanced heart failure patients awaiting heart transplantation.

AIMS: The value of Forrester's perfusion/congestion profiles assessed by invasive catheter evaluation in non-inotrope advanced heart failure patients listed for heart transplant (HT) is unclear. We aimed to assess the value of haemodynamic evaluation according to Forrester's profiles to predict events on the HT waitlist. METHODS AND RESULTS: All non-inotrope patients (n = 837, 79% ambulatory at listing) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 with right heart catheterization (RHC) were included. The primary outcome was a combined criteria of waitlist death, delisting for aggravation, urgent HT or left ventricular assist device implantation. Secondary outcome was waitlist death. The 'warm-dry', 'cold-dry', 'warm-wet', and 'cold-wet' profiles represented 27%, 18%, 27%, and 28% of patients, respectively. At 12 months, the respective rates of primary outcome were 15%, 17%, 25%, and 29% (P = 0.008). Taking the 'warm-dry' category as reference, a significant increase in the risk of primary outcome was observed only in the 'wet' categories, irrespectively of 'warm/cold' status: hazard ratios, 1.50; 1.06-2.13; P = 0.024 in 'warm-wet' and 1.77; 1. 25-2.49; P = 0.001 in 'cold-wet'. CONCLUSIONS: Haemodynamic assessment of advanced HF patients using perfusion/congestion profiles predicts the risk of the combine endpoint of waitlist death, delisting for aggravation, urgent heart transplantation, or left ventricular assist device implantation. 'Wet' patients had the worst prognosis, independently of perfusion status, thus placing special emphasis on the cardinal prominence of persistent congestion in advanced HF.