Frederic Pinaud

Notch3 Is a Major Regulator of Vascular Tone in Cerebral and Tail Resistance Arteries

Objective—Notch3, a member of the evolutionary conserved Notch receptor family, is primarily expressed in vascular smooth muscle cells. Genetic studies in human and mice revealed a critical role for Notch3 in the structural integrity of distal resistance arteries by regulating arterial differentiation and postnatal maturation. Methods and Results—We investigated the role of Notch3 in vascular tone in small resistance vessels (tail and cerebral arteries) and large (carotid) arteries isolated from Notch3-deficient mice using arteriography. Passive diameter and compliance were unaltered in mutant arteries. Similarly, contractions to phenylephrine, KCl, angiotensin II, and thromboxane A2 as well as dilation to acetylcholine or sodium nitroprusside were unaffected. However, Notch3 deficiency induced a dramatic reduction in pressure-induced myogenic tone associated with a higher flow (shear stress)-mediated dilation in tail and cerebral resistance arteries only. Furthermore, RhoA activity and myosin light chain phosphorylation, measured in pressurized tail arteries, were significantly reduced in Notch3KO mice. Additionally, myogenic tone inhibition by the Rho kinase inhibitor Y27632 was attenuated in mutant tail arteries. Conclusions—Notch3 plays an important role in the control of vascular mechano-transduction, by modulating the RhoA/Rho kinase pathway, with opposite effects on myogenic tone and flow-mediated dilation in the resistance circulation.

Paradoxical Role of Angiotensin II Type 2 Receptors in Resistance Arteries of Old Rats

The role of angiotensin II type 2 receptors (AT2Rs) remains a matter of controversy. Its vasodilatory and antitrophic properties are well accepted. Nevertheless, in hypertensive rats, AT2R stimulation induces a vasoconstriction counteracting flow-mediated dilation (FMD). This contraction is reversed by hydralazine. Because FMD is also decreased in aging, another risk factor for cardiovascular diseases, we hypothesized that AT2R function might be altered in old-rat resistance arteries. Mesenteric resistance arteries (250 &mgr;m in diameter) were isolated from old (24 months) and control (4 months) rats receiving hydralazine (16 mg/kg per day; 2 weeks) or water. FMD, NO-mediated dilation, and endothelial NO synthase expression were lower in old versus control rats. AT2R blockade improved FMD in old rats, suggesting that AT2R stimulation produced vasoconstriction. AT2R expression was higher in old rats and mainly located in the smooth muscle layer. In old rats, AT2R stimulation induced endothelium-independent contraction, which was suppressed by the antioxidant Tempol. Reactive oxygen species level was higher in old-rat arteries than in controls. Hydralazine improved FMD and NO-dependent dilation in old rats without change in AT2R expression and location. In old rats treated with hydralazine, reactive oxygen species level was reduced in endothelial and smooth muscle cells, and AT2R-dependent contraction was abolished. Thus, AT2R stimulation induced vasoconstriction through activation of reactive oxygen species production, contributing to decrease FMD in old-rat resistance arteries. Hydralazine suppressed AT2R-dependent reactive oxygen species production and AT2R-dependent contraction, improving FMD. Importantly, endothelial alterations in aging were reversible. These findings are important to consider in the choice of vasoactive drugs in aging.

In vitro protection of vascular function from oxidative stress and inflammation by pulsatility in resistance arteries

OBJECTIVE Resistance arteries remain subject to pulsatility, a potent regulator of large elastic artery tone and structure, but the effect is incompletely understood. Extracorporeal circulation during cardiac surgery is often associated with absence of pulsatility, which may affect vascular tone. To define the role of the vascular wall in the inflammatory process that may occur with or without pulsatility, we studied resistance arteries functions ex vivo. We measured vascular reactivity, oxidative stress, and inflammation in the arterial wall. METHODS Isolated rat mesenteric resistance arteries were mounted in an arteriograph and subjected to pulsatility or not in vitro. Arteries were perfused with a physiologic salt solution without circulating cells. RESULTS After 180 minutes, flow-mediated dilation was higher and pressure-induced myogenic tone lower in arteries subjected to pulsatility. Without pulsatility, reactive oxygen species and markers of inflammation (monocyte chemotactic protein 1 and tumor necrosis factor α) were higher than baseline. In perfused mesenteric beds under similar conditions, tumor necrosis factor α was higher in perfusate after 180 minutes of nonpulsatility (5.7 ± 1.6 pg/mL vs 1.1 ± 0.4 pg/mL; P < .01). In arteries treated with the antioxidant 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (tempol), flow-mediated dilation and myogenic tone were similar in nonpulsatile and pulsatile arteries; monocyte chemotactic protein 1 and nuclear factor κB expression levels were not increased in tempol-treated nonpulsatile arteries. CONCLUSIONS Absence of pulsatility in resistance arteries increased oxidative stress, which in turn induced inflammation and preferentially altered pressure and flow-dependent tone, which play a key role in control of local blood flow.

Influence of Sex on Mortality and Perioperative Outcomes in Patients Undergoing TAVR: Insights From the FRANCE 2 Registry

Henoch-Schonlein purpura (HSP) is a common autoimmune vasculitis in childhood. The detailed pathogenesis of HSP is still unclear, whereas several types of predisposing factors have been proved to be the initial step. The objectives of present study were to analyze the distribution of predisposing factors, association of the predisposing factors with clinical manifestations and HSP relapse/recurrence. 1200 children with HSP were recruited between January 2015 and December 2017. We reviewed their laboratory tests and medical histories associated with HSP onset. The annual incidence of HSP was 8.13–9.17 per 100 000 in Anhui province. HSP occurred more commonly in spring and winter than in summer with an obvious west-to-east gradient. Cutaneous purpura was the most prevalent manifestation (100%), followed by arthritis/arthralgias (43.67%), abdominal pain (40.17%) and renal involvement (18.17%). On admission, series of potential infections were identified in 611 patients (50.92%). The histories of allergy, injury, surgery, vaccination and tick bite were declared by 231 patients (19.25%), 15 patients (1.25%), 12 patients (1.00%), 4 patients (0.33%) and 3 patients (0.25%), respectively. However, predisposing factors could not be identified in 521 children with HSP (43.42%) yet. 123 cases (10.25%) relapsed or recurred more than one time; the mean number was 2.92, and the mean interval was 11.4 weeks. The infection is the most frequent predisposing factor regardless of clinical phenotypes and relapse/recurrence, whereas the clinical manifestations exhibit an obvious heterogenicity according to different predisposing factors.

Long-Delayed Localization of a Cardiac Functional Paraganglioma With SDHC Mutation

TO THE EDITOR: The evidence supporting the effectiveness of early screening of African Americans at average risk for colorectal cancer (CRC) is scarce. It is surprising that the American College of Physicians’ (ACP) guidance statement (1) recommends CRC screening in this group at age 40 years when there is no evidence that such a strategy is effective. A recent article from Gupta and colleagues (2) reported that increasing colonoscopy participation by 5% and 10% among African Americans aged 50 years or older detected 53% and 57% of CRC, respectively, and early screening of African Americans at age 45 years detected 52% of CRC. You and colleagues (3) further demonstrate that early-onset CRC was more prevalent among nonwhite patients who were either uninsured or insured by Medicaid (3). The results of these 2 studies have several implications that feed into the wider debate on social determinants of health and access to health care by the underserved, who are often disproportionately African American. First, simply implementing race-specific, early-age CRC screening policy for African Americans is unlikely to significantly increase early detection rates. Second, factors leading to reduced colonoscopy participation among African Americans need to be identified and appropriately addressed. African Americans are a diverse group of self-identified Americans with varying amounts of African genetic admixture. Classifying this group as having aboveaverage risk for CRC presupposes that race, as a proxy of ancestral African genomic identification, predicts CRC disease clusters in the African American population. If that is the case, biological markers that make African Americans more likely to develop CRC earlier should be identifiable and would lend credence to the argument for earlier screening. Furthermore, there should be a corresponding clustering of CRC in ancestral populations in Africa; however, this is not the case, because the available evidence shows that the incidence of CRC in Africa is low (4). Therefore, the observed increased incidence of CRC among African Americans is probably related to environmental, lifestyle, and socioeconomic factors rather than biological or genetic factors (4). While the medical community eagerly awaits the outcome of ongoing studies on the effectiveness of initiating early CRC screening in African Americans, strategies to improve access to CRC screening and colonoscopy participation among African Americans aged 50 years or older should be actively pursued in addition to timely case detection of symptomatic young adults and sustained advocacy on healthier lifestyle choices.

Endovascular treatment of inoperable acute type A dissection via the transapical approach

An 83-year-old female patient was admitted to our department for thoracic pain. Her medical history composed of hypertension, atrial fibrillation, two thoracic aortic endoprostheses for penetrating aortic ulcer, an aorto-bi-iliac endoprosthesis for subrenal aortic aneurysm, as well as a right ilio-femoral bypass. ( Panel A ). At admission, the computer tomography (CT) scan showed a dissecting haematoma of the ascending aorta, with heavy calcifications …

Incidence et évolution des images thrombotiques dans la veine jugulaire interne après cathétérisme de Swan-Ganz en chirurgie cardiaque

OBJECTIVES Insertion of Swan-Ganz catheter for a few days may be necessary in cardiac surgery. This study was aimed at determining the incidence and the evolution of thrombotic images within the internal jugular vein as well as assessing their association with the presence of a prolonged fever at postoperative day 7 in the lack of any documented infection. MATERIAL AND METHODS All the patients undergoing cardiac surgery had a two-dimensional ultrasonography of internal jugular veins preoperatively, at discharge (day 7) and at postoperative day 90 if thrombotic images were seen at day 7. RESULTS Sleeve-like and compact thrombotic images have been observed in site of venipuncture in 52 patients (70.3%). None had any residual thrombotic image 90 days after the operation. No clinical thromboembolic migration has been observed. There was no statistical association between the presence of a thrombotic image at the ultrasonography and the duration of catheterization. Moreover, there was no association between the anticoagulation before, during and after the surgery and the presence of a thrombotic image. We found a non-significant association between fever at day 7 and the presence of a thrombotic image within the internal jugular vein. CONCLUSION Thrombotic images in the internal jugular vein after catheterization are frequent and disappear at day 90. The limited sample size of this study does not provide strong evidence of the role of jugular thrombi in the prolongation of fever after cardiac surgery.

TCT-84 Outcomes of Transcatheter Aortic Valve Replacement without predilation of the aortic valve: Insights from 1942 patients included in the SOURCE 3 Registry

nos: 85 88

0179: Transcatheter valve-in-valve implantation in patients with failed aortic bioprosthesis: immediate and medium-term outcomes of 15 procedures

Background TAVI offers an attractive option for patients with failed bioprosthesis and high operative risk (valve-in-valve concept). Purpose The objective of this study was to analyze outcomes of patients with failed aortic bioprosthesis undergoing transcatheter aortic valve-in-valve implantation. Methods From January 2012 to January 2015, 15 patients with degenerated aortic valve bioprosthesis underwent transcatheter aortic valve-in-valve implantation in our institution. Mean patient age was 82±6 years. Mean logistic Euroscore was 36±16% and mean STS score was 16±14%. The mean follow-up was 260±316 days. Results The failing bioprosthesis were Cryolife O’brien in 5 patients, Carpentier Edwards in 5 patients, Medtronic mosaic in 4 patients and Mitroflow in 1 patient. Bioprosthesis mode of failure was stenosis (n=6), regurgitation (n=5), or combined stenosis and regurgitation (n=4). The mean degenerative time was 11.15±6.1 years. Implanted devices included Medtronic CoreValve (n=6) and Edwards SAPIEN (n=9). Successful implantation of a transcatheter aortic valve-in-valve with the patient leaving the catheterization laboratory alive was achieved in all patients. Adverse procedural outcomes included initial device malposition in 3 cases requiring a second valve, retroperitoneal hematoma in 1 patient, permanent pacemaker in 1 patient, Stroke in 1 patient and acute renal failure in 1 patient. The mean transvalvular gradient passed from 48.7±17.63 to 18.32±9.3mmHg in stenotic degenerated bioprosthesis. No significant aortic regurgitation was observed post-implantation. During hospitalization, 1 patient developed myocardial infarction. The medium inhospital stay was 13.4±7.7 days. During later follow-up, there was no death, no myocardial infarction and no stroke or TIA. 2 patients were hospitalized for heart failure. Conclusion Transcatheter aortic valve-in-valve implantation seems to be feasible and safe in both stenotic and regurgitant degenerative bioprosthesis.

Endovascular treatment of iatrogenic aortic graft injury after sternal puncture

We report the case of a 71-year old woman who had previously undergone supra-aortic trunk transposition via a median sternotomy, along with endovascular thoracic aortic stent-graft repair. During the diagnostic sternal puncture for a recently discovered acute lymphoblastic leukaemia, an accidental graft injury occurred. For this patient, who was not a surgical candidate, endovascular treatment with a covered stent (endograft) was performed, with uneventful postoperative follow-up. This case report illustrates the limitations of sternal puncture in patients with a previous sternotomy, and discusses the possibility of endovascular treatment in the event of aortic graft injury, given easy accessibility and favourable aortic neck anatomy.