Background: While endothelial dysfunction is suggested to contribute to heart failure with preserved ejection fraction pathophysiology, understanding the importance of the endothelium alone, in the pathogenesis of diastolic abnormalities has not yet been fully elucidated. Here, we investigated the consequences of specific endothelial dysfunction on cardiac function, independently of any comorbidity or risk factor (diabetes or obesity) and their potential effect on cardiomyocyte. Methods: The ubiquitine ligase Pdzrn3 , expressed in endothelial cells (ECs), was shown to destabilize tight junction. A genetic mouse model in which Pdzrn3 is overexpressed in EC (iEC-Pdzrn3) in adults was developed. Results: EC-specific Pdzrn3 expression increased cardiac leakage of IgG and fibrinogen blood-born molecules. The induced edema demonstrated features of diastolic dysfunction, with increased end-diastolic pressure, alteration of dP/dt min, increased natriuretic peptides, in addition to limited exercise capacity, without major signs of cardiac fibrosis and inflammation. Electron microscopic images showed edema with disrupted EC-cardiomyocyte interactions. RNA sequencing analysis of gene expression in cardiac EC demonstrated a decrease in genes coding for endothelial extracellular matrix proteins, which could be related to the fragile blood vessel phenotype. Irregularly shaped capillaries with hemorrhages were found in heart sections of iEC- Pdzrn3 mice. We also found that a high-fat diet was not sufficient to provoke diastolic dysfunction; high-fat diet aggravated cardiac inflammation, associated with an altered cardiac metabolic signature in EC- Pdzrn3 mice, reminiscent of heart failure with preserved ejection fraction features. Conclusions: An increase of endothelial permeability is responsible for mediating diastolic dysfunction pathophysiology and for aggravating detrimental effects of a high-fat diet on cardiac inflammation and metabolism.

OBJECTIVES: The aim of this retrospective multicentre study was to investigate and compare clinical outcomes of unilateral and bilateral antegrade cerebral perfusion (ACP) strategies on cerebral protection during surgery for type A aortic dissection. METHODS: Data from 646 patients who underwent surgical repair of thoracic type A aortic dissection using unilateral and bilateral ACP with moderate hypothermic circulatory arrest in 3 cardiac surgical institutions between 2008 and 2018 were analysed. Propensity matching was performed to assess which technique ensured better outcomes. RESULTS: Unilateral and bilateral ACP techniques were performed in 250 (39%) and in 396 (61%) patients, respectively. Propensity score analysis identified 189 matched pairs. In the matched cohort, the lowest core temperature was 27.5°C and 28°C in the bilateral and unilateral groups, respectively (P < 0.001). The unilateral technique required significantly shorter aortic cross-clamp and cardiopulmonary bypass times than bilateral technique [82 min vs 100 min (P < 0.001); 170 min vs 195 min (P < 0.001)]. The 30-day mortality was comparable (P = 0.325). The bilateral group reported a significantly higher incidence of permanent neurologic deficits (P < 0.001), left brain hemisphere stroke (P = 0.007) and all-combined complications (P < 0.001). Ten-year survival was comparable (P = 0.45). CONCLUSIONS: Unilateral and bilateral ACP are both valid brain protection strategies in the landscape of aortic arch surgery. While admitting all the study limitations, unilateral technique could offer some clinical advantages. Clinical registration number: 76049

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.

Aims: Short-term mechanical circulatory support (STMCS) may be used as an intentional escalation strategy to treat refractory cardiogenic shock (rCS). However, with growing technical possibilities, making the right choice at the right time can be challenging. We established a shock team in January 2013 comprising a cardiac anaesthetist–intensivist, an interventional cardiologist, and a cardiac surgeon. Since then, a diagnosis of rCS has triggered a multidisciplinary team meeting based on a common algorithm. This study aimed to compare the decision-making process for STMCS for rCS before (2007–2013) and after (2013–2019) the creation of the shock team. Methods and results: This before-and-after cohort study was conducted over a 156-month period. Post-cardiotomy rCS were excluded. The primary outcome was a 1-year survival rate. In total, 250 consecutive adult patients were included in the analysis (84 in the control group and 166 in the shock team group). At baseline, the CardShock score was not different between the two groups (5[3–5] vs. 5[4–6], P = 0.323). The 1-year survival rate was significantly higher in the shock team group compared with the control group (59% vs. 45%, P = 0.043). After a Cox regression analysis, the shock team intervention was independently associated with a significantly improved 1-year survival rate (HR: 0.592, 95% CI: 0.398–0.880, P = 0.010). Conclusion: A multidisciplinary shock team-based decision for STMCS device implantation in rCS is associated with better 1-year survival rates.

Background: Genome-wide association studies have revealed robust associations of common genetic polymorphisms in an intron of the PHACTR-1 (phosphatase and actin regulator 1) gene (chr6p24), with cervical artery dissection, spontaneous coronary artery dissection, and fibromuscular dysplasia. The aim was to assess its role in the pathogenesis of cervical artery dissection or fibromuscular dysplasia. Methods: Using various tissue-specific Cre-driver mouse lines, Phactr1 was deleted either in endothelial cells using 2 tissue-specific Cre-driver (PDGFB [platelet-derived growth factor B]-Cre^ERT2 mice and Tie2 [tyrosine kinase with immunoglobulin and EGF homology domains]-Cre) and smooth muscle cells (smooth muscle actin-Cre^ERT2) with a third tissue-specific Cre-driver. Results: To test the efficacy of the Phactr1 deletion after cre-induction, we confirmed first, a decrease in Phactr1 transcription and Phactr1 expression in endothelial cell and smooth muscle cell isolated from Phactr1^iPDGFB and Phactr1^iSMA mice. Irrespective to the tissue or the duration of the deletion, mice did not spontaneously display pathological phenotype or vascular impairment: mouse survival, growth, blood pressure, large vessel morphology, or actin organization were not different in knockout mice than their comparatives littermates. Challenging vascular function and repair either by angiotensin II–induced hypertension or limb ischemia did not lead to vascular morphology or function impairment in Phactr1-deleted mice. Similarly, there were no more consequences of Phactr1 deletion during embryogenesis in endothelial cells. Conclusions: Loss of PHACTR-1 function in the cells involved in vascular physiology does not appear to induce a pathological vascular phenotype. The in vivo effect of the intronic variation described in genome-wide association studies is unlikely to involve downregulation in PHACTR-1 expression.

OBJECTIVES: Our goal was to provide a picture of left ventricular assist device (LVAD) activity in France between 2007 and 2016 based on the multicentric ASSIST-ICD registry. METHODS: We retrospectively collected 136 variables including in-hospital data, follow-up survival rates and adverse events from 671 LVAD recipients at 20 out of 24 LVAD implant centres in France. The average follow-up time was 1.2 years (standard deviation: 1.4); the total follow-up time was 807.5 patient-years. RESULTS: The included devices were the HeartMate II®, HeartWare LVAS® or Jarvik 2000®. The overall likelihood of being alive while on LVAD support or having a transplant (primary end point) at 1, 2, 3 and 5 years postimplantation was 65.2%, 59.7%, 55.9% and 47.7%, respectively, given a cumulative incidence of 29.2% of receiving a transplant at year 5. At implantation, 21.5% of patients were on extracorporeal life support. The overall rate of cardiogenic shock at implantation was 53%. The major complications were driveline infection (26.1%), pump pocket or cannula infection (12.6%), LVAD thrombosis (12.2%), ischaemic (12.8%) or haemorrhagic stroke (5.4%; all strokes 18.2%), non-cerebral haemorrhage (9.1%) and LVAD exchange (5.2%). The primary end point (survival) was stratified by age at surgery and by the type of device used, with inference from baseline profiles. The primary end point combined with an absence of complications (secondary end point) was also stratified by device type. CONCLUSIONS: The ASSIST-ICD registry provides a real-life picture of LVAD use in 20 of the 24 implant centres in France. Despite older average age and a higher proportion of patients chosen for destination therapy, survival rates improved compared to those in previous national registry results. This LVAD registry contrasts with other international registries because patients with implants have more severe disease, and the national policy for graft attribution is distinct. We recommend referring patients for LVAD earlier and suggest a discussion of the optimal timing of a transplant for bridged patients (more dismal results after the second year of support?).