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Regulation of endothelial barrier function is critical for vascular homeostasis but a comprehensive understanding of sepsis-induced endothelial injury involved in organ failure is lacking. We have previously demonstrated that recombinant human Angiopoietin-like-4 (ANGPTL4) protects vascular integrity in the heart, reduces cardiac edema and no-reflow acutely after acute myocardial infarction (AMI). We have also shown that ANGPTL4 has protective effects on the cerebrovascular and functional damage after ischaemic stroke that shares some pathophysiological factors with AMI. Given the strong association between vascular barrier integrity and endothelial injury markers for predicting higher mortality in shocks, we here sought to evaluate the cardiovascular impact of a novel pharmacological strategy that preserves microvascular integrity aimed at reducing endothelial damage and fluid extravasation, in order to improve perfusion and reduce organ failure and death. Septic shock was induced in adult mice using lipopolysaccharides (LPS). Vascular leakage (total weight/dry weight) was assessed in highly metabolic tissues such as liver, kidneys, lungs and heart by gravimetry in control mice vs mice injected with recombinant human Angiopoietin-like-4 (ANGPTL4). To go further, integrity of tight junctions was studied by using endothelial cells treated with LPS and treated or not with ANGPTL4. Following septic shock, our results demonstrate that injection of recombinant human Angiopoietin-like-4 (ANGPTL4) was able to protect vascular barrier integrity by decreasing fluid extravasation in cardiorespiratory system. In addition, we demonstrate that ANGPTL4 was able to preserve the integrity of endothelial cells junctions after LPS treatment. These results show that ANGPTL4 is a regulator of endothelial barrier integrity during septic shock. This discovery of the vascular protective effects of ANGPTL4, thus being crucial for preventing endothelial damage during septic shock, is one of the first examples of the validity of applying vascular permeability-limiting drugs in shock states. Its therapeutic potential in other types of shocks is also presently under investigation. [ABSTRACT FROM AUTHOR]

This study sought to investigate patient intermediate-term outcomes after transcatheter pulmonary valve replacement (TPVR) with Edwards SAPIEN valve. The Edwards SAPIEN valve, initially designed for percutaneous aortic valve replacement, has been approved for TPVR in patients with dysfunctional right ventricular outflow tracts (RVOT), but only short-term follow-up has been reported. From 2011 to 2016, 62 patients undergoing successful TPVR using the SAPIEN XT valve were consecutively included into the study. Primary efficacy and safety endpoints were defined as freedom from valve-reintervention and freedom from infective endocarditis at last follow-up, respectively. The primary efficacy outcome was met for 87,1% patients after a mean follow-up of 55 ± 21 months, corresponding to a freedom of reintervention at 5 years of 89% (95% CI 74.8–95.6%). Reinterventions were exclusively due to recurrent obstruction, no significant valvular insufficiency was observed. One case of infective endocarditis was reported, corresponding to a rate of 0.35% per patient-year (95% CI 0.01–2.00%). At 5 years freedom from infective endocarditis was 98.4% (95% CI 89.1–99.8%) (Fig. 1). Six patients died or were transplanted due to advanced cardiac failure, without relationship with TPVR. In univariate analysis, reintervention was associated with young age, a smaller tube-graft, a higher pulmonary valve gradient after the procedure and a ratio of largest implanted stent diameter to invasive balloon conduit diameter over 1.35. This study confirms the mid-term safety and efficacy of the Edwards SAPIEN XT valve in patients with dysfunctional RVOT, and identifies a patient profile associated with an uncertain benefit-risk balance. [ABSTRACT FROM AUTHOR]

This study sought to report the specific considerations and implications of percutaneous edge-to-edge repair in one case of severe systemic tricuspid regurgitation (STR). In congenitally-corrected transposition of great arteries (ccTGA) tricuspid valve results spontaneously in systemic position. In this situation, progressive STR and systemic right ventricular (SRV) dysfunction are frequently observed, leading ultimately to altered functional capacities and pulmonary edema. In this setting surgical valve repair or replacement is challenging given the underlying SRV failure, therefore heart transplant is usually preferred. However, recent studies have underlined the reliability of edge-to-edge repair for secondary severe tricuspid and mitral regurgitation. Few data are currently available concerning the percutaneous management of STR. We report about the case of a 59 year-old man presenting with dyspnea and mild peripheral edema. He was known for non-operated ccTGA with SRV ejection fraction (EF) of 25%, and severe STR, defined as an effective regurgitant orifice area of 40 mm2. The patient was in theory eligible for heart transplant but a percutaneous approach was first attempted. The procedure was performed under general anesthesia, transesophageal echocardiography guidance and through a femoral vein route. A MitraClip XTR device (Abbott Vascular, Santa Clara, CA) was successfully implanted between the septal and the anterior leaflets, without any complication (Fig. 1). After the procedure the STR improved dramatically from grade IV to I. After 2 years follow-up the patient is still asymptomatic and free from severe STR, concomitantly SRV EF improved up to 32% under optimal medical treatment. Percutaneous edge-to-edge therapy of STR in ccTGA seems to be feasible, safe and effective to reduce regurgitation grade, to limit SRV dilatation and to improve patient symptoms. [ABSTRACT FROM AUTHOR]

Congenital portosystemic shunts (CPSS) are rare and underdiagnosed abdominal vascular malformations. Their relationship with cardiovascular (CV) disorders are poorly reported. Herein, we describe CV disorders associated with CPSS in a large cohort to propose adequate diagnosis and management. Among 168 children referred for a CPSS (1996–2019), those presenting at least one clinically significant CV disease including congenital heart diseases (CHD), heart failure (HF), pulmonary hypertension (PH) and/or hepatopulmonary syndrome (HPS) were included. CV disorders were detected using echocardiography complemented by right-sided heart catheterization and/or lung perfusion radionuclide when appropriate. 46/168 children with CPSS (27,4%) were included. In 36 patients, endovascular or surgical CPSS closure was required, including 24 for CV indications. CHD was present in 28 patients (16,6%); 7 had heterotaxy (4,1%). HF occurred in 21 neonates, diagnosed prenatally in 7, including 13 with CHD. HF decreased after cardiac surgery in 10 with CHD but also spontaneously before the age of 3 years in 8 except one without CHD. In 11 patients (mean age: 11 ± 5.2 years) CPSS were diagnosed as part of a work up for fixed PH (mean pressures 46 ± 15.1 mmHg, pulmonary vascular resistances 7 ± 2.5UW/m2). One of them died before CPSS closure, while PH remained stable despite CPSS closure in 10 patients, of which 2 then required lung transplantation. In 6 patients (median age: 5.5 years), hypoxia revealed HPS which resolved within 2 years of CPSS closure. CV disorders are frequently associated with CPSS including CHD with/without heterotaxy. HF is found in fetuses and neonates, regressing in most cases. Later, HPS and PH may develop. After CPSS closure, HPS is reversible while PH may only stabilize. Perinatal HF, complex CHD, heterotaxy, unusual course of CHD, HPS and PH should raise the possibility of CPSS. Conversely CV complications should be searched for in patients with CPSS. [ABSTRACT FROM AUTHOR]

The COCCINELLE study is a nationwide retrospective French cohort set up to evaluate the risk of radiation associated cancer in patients who undergone cardiac catheterization (CC) procedures for diagnosis or treatment of congenital heart disease during childhood [1]. Children who undergone CC procedures from 01/01/2000 to 31/12/2013 before the age of 16 in one of the 15 pediatric cardiology departments which perform pediatric CC in mainland France were included. The follow-up started at the date of the first recorded CC procedure until the exit date, i.e. the date of death, the date of first cancer diagnosis, the date of the 18th birthday, or the 31/12/2015, whichever occurred first. The cohort was linked to the National Childhood Cancer Registry to identify patients diagnosed with cancer and with the French National Directory for the Identification of Natural Persons to retrieve the patients' vital status. An external comparison was conducted using standardized incidence ratios (SIR). Breslow and Day's approximation was used to estimate 95% confidence intervals (CI) for the SIRs [2]. A total of 17,104 children were included in the cohort and followed for 110,335 person-years, with 22,227 CC procedures collected. Among the patients, 81.6% received only one procedure. Fifty-nine cancer cases were observed in the cohort. SIRs were increased for all-cancer (SIR = 3.8, 95% CI 2.9, 4.9), leukemia (SIR = 3.3, 95% CI 2.0, 5.4), lymphoma (SIR = 14.9, 95% CI 9.9, 22.5) and solid cancers excluding central nervous system tumors (SIR = 3.3, 95% CI 2.0, 5.5) compared with the general population. Increased risks of cancer were observed. Potential explanations include shared genetic or environmental factors, immunosuppression drugs, and exposure to medical ionizing radiation procedures. The dose-response analysis between ionizing radiation doses received during CCs and cancer occurrence will allow to address this question. [ABSTRACT FROM AUTHOR]

Although capillary leakage is a major feature of systemic inflammatory response syndrome (SIRS) associated with shocks, molecular mechanisms remain uncharacterized in humans. Patients with severe cardiogenic shock were recruited from La Pitié-Salpêtrière intensive care unit (ICU) and RNAseq analysis of circulating monocytes was performed. Thirty-eight genes associated with capillary leakage were thus identified. Beyond them, amphiregulin is a ligand of EGF receptor involved in angiogenesis, and its expression is triggered by lipopolysaccharides in monocytes. We first confirmed association between AMPHIREGULIN plasma level and vascular leakage in a validation cohort of 77 cardiogenic shock patients. We here hypothesize that AMPHIREGULIN may play a role in SIRS-induced capillary leakage. The aim of the project is to characterize its mechanisms of action. Vascular permeability was compared in amphiregulin-KO or WT-mice using a model of LPS-induced capillary leakage. Total/dry weight ratio (W/D ratio) of lungs, heart, liver and kidney as well as quantification of Evans blue leakage were used to quantify vascular permeability. In two preliminary experiments (n = 15 KO and 9 WT), lung W/D ratio of amphiregulin-KO mice was significantly reduced compared to WT-mice after LPS injection (median 4.27 [IQR 4.16-4.42] vs. 4.53 [4.41-4.61], P < 0.01). A similar trend was quantified in the liver (3.38 [3.3-3.49] vs. 3.52 [3.38-3.56], P = 0.096). In contrast, W/D ratio in other organs were not affected. These preliminary results indicate that AMPHIREGULIN may be an important regulator of vascular permeability in SIRS induced by cardiogenic shock. Further experiments are presently ongoing to confirm these results. [ABSTRACT FROM AUTHOR]

Patent ductus arteriosus (PDA) is very common in extremely low birth weight babies and may contribute to prolonged mechanical ventilation, bronchopulmonary dysplasia, renal failure, periventricular leukomalacia and necrotizing enterocolitis. When PDA closure is indicated with failure of medical therapy (cyclooxygenase inhibitors or paracetamol), surgical ligation is usually performed with excellent results. Transcatheter closure has been recently developed with promising results but comparative studies with surgical ligation are lacking. To compare results and outcomes after transcatheter closure using the Amplatzer Piccolo device versus surgical closure in 2 matched groups of pre-term infants weighing ≤ 3000 g. One hundred and forty seven babies (3 tertiary centres) were retrospectively analysed. Sixty-four patients who underwent transcatheter closure were compared with 83 matched surgical patients, using Wilcoxon signed-rank tests. PDA closure was successful in all surgical and transcatheter cases. During NICU course, mortality was 6.3% (n = 4) after transcatheter closure and 12% (n = 10) after surgery (P = 0.24). Median duration of mechanical ventilation was shorter after transcatheter closure than after surgical ligation (3 vs. 5 days, P = 0.035). In babies undergoing duct closure before 4 weeks of age the difference between transcatheter and surgical closure for mechanical ventilation during the NICU course was even more pronounced (3 vs. 9 days, P = 0.022). When transcatheter closure was performed before 4 weeks, babies were discharged home earlier as compared to those who underwent closure later in life (39 + 1 vs. 41 + 5 weeks, P = 0.021). Such difference was not found in the surgical group. Transcatheter PDA closure in low birth weight babies is safe, effective and associated with improved mechanical ventilation as compared to surgery. It may offer shorter hospital stay when performed earlier in life. [ABSTRACT FROM AUTHOR]

Objective The aim of the study was to compare the short-term outcome after patent ductus arteriosus (PDA) percutaneous closure versus surgical ligation in extremely preterm infants. Methods We retrospectively performed a mono-centric matched case-control study. Cases were preterm infants born before 28 weeks of gestation with PDA percutaneous closure performed in Nantes University hospital. Each case was matched, for gestational age and post-natal age at intervention, with 2 controls who had PDA surgical ligation. The main criterion was the rate of extubated patients 2 days after the procedure. Results We included in the analysis 14 percutaneous closures and 28 surgical ligations performed between January 2006 and December 2017. Two days after the procedure, 7.1% patients were off mechanical ventilation in the surgical group versus 50% in the percutaneous group ( P = 0.001). Mean duration of mechanical ventilation was 5.4 days (± 5.0) in the percutaneous group versus 12.5 days (± 11.1) in the surgical group ( P = 0.009). No complication of percutaneous closure was noticed. Conclusion Percutaneous closure of PDA allowed a faster pulmonary recovery and mechanical ventilation cessation in preterm infant born before 28 weeks of gestation with the same efficacy and without any related complication than surgery. [ABSTRACT FROM AUTHOR]

The coronary angiography among patients with coronary artery bypass graft (CABG) are more complex procedures with more X-ray exposure, longer compared to conventional coronary angiography. Image fusion is a new technology allowing a fusion in real-time of a 3D model obtained by reconstruction of computed tomography (CT) images with fluoroscopic images. To evaluate the contribution of image fusion in coronary angiography for the detection of CABG. A prospective study over 9 months, single center comparing the use of image fusion to conventional coronary angiography. All patients coming for angiographic control of CABG were included in the study. Patients who had previously (for another indication) a chest CT with injection of contrast media were the fusion image group, patients without prior injected chest CT constituted the control group. For patients in the fusion group, the aorta, the CABG, sternotomy sutures, the bronchi and a vertebra were reconstructed in 3D from CT acquisitions and these images were incorporated in real-time on fluoroscopic images. The following parameters were reported in both groups and compared: search time of CABG, procedure time, X-Ray exposure and the amount of contrast. 59 patients were included, 13 in the fusion image group, 46 in the control group. There were not significant differences between the 2 groups in terms of general characteristics patients and procedures. The search time of CABG was significantly shorter in the fusion group of images in the control group (16.04 min±13.2 min vs 6.4 min±4.7 min, p=0.002), as well as procedure time (31.5 min±15.2 min vs 19.4 min± 6.8 min, p = 0.007), fluoroscopy time (14.76 min±8.3 min vs 9.3 min±4.2 min, p = 0.04), Air KERMA (822.9 mGy±475.5 mGy vs 569.1 mGy±242.4 mGy, p = 0.01) and amount of iodinated contrast (121 cc ± 43.5 cc vs 88.2 cc±30.8 cc, p = 0.01). 3D reconstruction of CABG from CT with real-time fusion on coronary angiography images may shorten the search time of CABG, procedure time, X-Ray exposure and the use of iodinated contrast compared to standard coronary angiography for diagnostic purposes in patients with CABG. Abstract 0498 – Figure: 3D picture merged with the real-time fluoroscopic [ABSTRACT FROM AUTHOR]

Background Transcatheter aortic valve replacement (TAVR) is quickly spreading as an efficient and safe therapy for the treatment of aortic valve stenosis in patients denied for surgery. There is no clear guideline established regarding anesthetic modalities to perform TAVR procedures. Objective This study was designed to assess the superiority of the local anesthesia for transfemoral TAVR, regarding major adverse events occuring in the early postoperative time. Methods From January 2014 to June 2015, 236 consecutive patients were included in the study (99 under general anesthesia [GA] and 137 under local anesthesia [LA]). The primary endpoint was a combination of MACE, rehospitalization for heart failure, acute kidney injury (AKI) stage 2 or 3, lifethreatening bleeding, major vascular complication, cardiac or rythmologic reintervention and/or haemodynamic instability, in the first 30 days after TAVR (each defined by VARC-2 criteria). Results Baseline characteristics were similar between the two groups. Conversion to general anesthesia occured in only 2 cases and procedural success was 94.9% ( p =NS). The combined endpoint was reached in 45 GA patients and in 41 LA patients ( p =0.02). We observed significantly less AKIevents in LA patients (9 vs 22; p <0.001), less rehospitalization (0 vs 4; p =0.02) and less vascular access site complications (15 vs 29; p <0.001). Postoperative echocardiographic results were similar in both groups. Secondary analysis revealed a shorter hospital stay (9±6.2 days vs 11.4±6.1 days; p =0.003) and shorter ICU stay (2.2±3.9 days vs 3.4±3.6 days; p =0.016) in LA patients.Fig. 1 Conclusion Local anesthesia significantly reduced the incidence of major adverse events after transfemoral TAVR, especially AKI and vascular access site complications (main predictors of early death after TAVR), without any significant change in echocardiographic results or procedural success. The author hereby declares no conflict of interest Primary endpoint and echocardiographic results [ABSTRACT FROM AUTHOR]

Aims We aimed to determine the correlation between optical frequency-domain imaging (OFDI) and micro-computed tomography (mCT) in the quantitative and qualitative assessment of ABSORB® bioresorbable vascular scaffold (BVS) in a bench test of multiple bifurcation technique. Method BVS were deployed in bifurcation silicon phantoms divided into two benches. Bench A is a LAD-diagonal bifurcation with a 40° angle and bench B, a left main bifurcation with a 70° angle. Finet’s law was respected. Different bifurcation techniques (provisional T stenting, kissing balloon, mini crush and culotte) were performed with a total of 16 procedures, 8 for each bench. All procedures were imaged by OFDI and mCT. BVS area, lumen area, number of struts, maximal stent thickness, disruption, lumen protrusion and deformation were the parameters collected. The analysis was performed in each segment, proximal, bifurcation and distal. Results In bench A, we found no differences between OFDI and mCT for each proximal, bifurcation and distal segments concerning BVS area, lumen area, number of struts, maximal stent thickness, fractures, lumen protrusion, BVS deformation or BVS fragments. In the proximal segment, length was higher in mCT (13.2mm vs 10.4mm; p<0.0001) and there was more malapposition detected in mCT (75% vs 0%, p=0.007). In bench B, for the proximal segment, lumen area was higher (13.7mm 2 vs 13.mm 2 , p=0.01) and we found more BVS malapposition in mCT (100% vs 0%, p =0.0002). All the other parameters were similar. In each bench, the apposition defect measured by mCT remained minimal. Conclusion We demonstrated an excellent correlation between OFDI and mCT which is considered as the gold standard to evaluate stent in bench tests. In vitro techniques can now be validated in vivo using OFDI. [ABSTRACT FROM AUTHOR]