Trends in aortic valve replacement for aortic stenosis: a French nationwide study.

AIMS: Transcatheter aortic valve replacement (TAVR) as an alternative to surgical aortic valve replacement (SAVR) has profoundly changed the management of patients with aortic valve stenosis (AS). Large unbiased nationwide data regarding TAVR implementation, impact on SAVR and their respective outcomes are scarce. METHODS AND RESULTS: Based on a French administrative hospital-discharge database, we collected data on all consecutive aortic valve replacements (AVRs) performed in France for AS between 2007 and 2019 [106 253 isolated SAVR (49%), 46 514 combined SAVR (21%), and 65 651 TAVR (30%)]. The number of AVR linearly increased between 2007 and 2019 (from 10 892 to 23 109, P for trend < 0.0001) due to a marked increase in TAVR (from 253 to 13 030, P for trend < 0.0001), while SAVR increased up to 2013 and then declined (10 892 in 2007, 12 699 in 2013, and 10 079 in 2019). The Charlson index decreased linearly for TAVR, but in two steps for SAVR (2011 and 2017). In-hospital mortality rates of both SAVR and TAVR declined (both P for trend < 0.0001) and were similar or lower for TAVR than for isolated SAVR in patients 75 years or above in the last 3 years (2017-19). Complication rates of TAVR also declined but permanent pacemaker rates remained high and length of stay substantial (16.7% and median 6 days, respectively, in 2017-19). CONCLUSION: The number of AVR has doubled in a decade and TAVR has become the dominant form of AVR in 2018. The improvement in patient profiles seems to have anticipated the demonstrated benefit of TAVR in intermediate and low-risk patients. In patients 75 years or older, TAVR should be considered as the first option. We also highlight two important areas for improvement, the high permanent pacemaker rates, and the long length of stay even in the contemporary era. Our results may have major implications for clinical practice and policymakers.

Trends in aortic valve replacement for aortic stenosis: a French nationwide study.

AIMS: Transcatheter aortic valve replacement (TAVR) as an alternative to surgical aortic valve replacement (SAVR) has profoundly changed the management of patients with aortic valve stenosis (AS). Large unbiased nationwide data regarding TAVR implementation, impact on SAVR and their respective outcomes are scarce. METHODS AND RESULTS: Based on a French administrative hospital-discharge database, we collected data on all consecutive aortic valve replacements (AVRs) performed in France for AS between 2007 and 2019 [106 253 isolated SAVR (49%), 46 514 combined SAVR (21%), and 65 651 TAVR (30%)]. The number of AVR linearly increased between 2007 and 2019 (from 10 892 to 23 109, P for trend < 0.0001) due to a marked increase in TAVR (from 253 to 13 030, P for trend < 0.0001), while SAVR increased up to 2013 and then declined (10 892 in 2007, 12 699 in 2013, and 10 079 in 2019). The Charlson index decreased linearly for TAVR, but in two steps for SAVR (2011 and 2017). In-hospital mortality rates of both SAVR and TAVR declined (both P for trend < 0.0001) and were similar or lower for TAVR than for isolated SAVR in patients 75 years or above in the last 3 years (2017-19). Complication rates of TAVR also declined but permanent pacemaker rates remained high and length of stay substantial (16.7% and median 6 days, respectively, in 2017-19). CONCLUSION: The number of AVR has doubled in a decade and TAVR has become the dominant form of AVR in 2018. The improvement in patient profiles seems to have anticipated the demonstrated benefit of TAVR in intermediate and low-risk patients. In patients 75 years or older, TAVR should be considered as the first option. We also highlight two important areas for improvement, the high permanent pacemaker rates, and the long length of stay even in the contemporary era. Our results may have major implications for clinical practice and policymakers.

TRI-SCORE: a new risk score for in-hospital mortality prediction after isolated tricuspid valve surgery.

AIMS: Isolated tricuspid valve surgery (ITVS) is considered to be a high-risk procedure, but in-hospital mortality is markedly variable. This study sought to develop a dedicated risk score model to predict the outcome of patients after ITVS for severe tricuspid regurgitation (TR). METHODS AND RESULTS: All consecutive adult patients who underwent ITVS for severe non-congenital TR at 12 French centres between 2007 and 2017 were included. We identified 466 patients (60 ± 16 years, 49% female, functional TR in 49%). In-hospital mortality rate was 10%. We derived and internally validated a scoring system to predict in-hospital mortality using multivariable logistic regression and bootstrapping with 1000 re-samples. The final risk score ranged from 0 to 12 points and included eight parameters: age ≥70 years, New York Heart Association Class III-IV, right-sided heart failure signs, daily dose of furosemide ≥125 mg, glomerular filtration rate <30 mL/min, elevated bilirubin, left ventricular ejection fraction <60%, and moderate/severe right ventricular dysfunction. Tricuspid regurgitation mechanism was not an independent predictor of outcome. Observed and predicted in-hospital mortality rates increased from 0% to 60% and from 1% to 65%, respectively, as the score increased from 0 up to ≥9 points. Apparent and bias-corrected areas under the receiver operating characteristic curves were 0.81 and 0.75, respectively, much higher than the logistic EuroSCORE (0.67) or EuroSCORE II (0.63). CONCLUSION: We propose TRI-SCORE as a dedicated risk score model based on eight easy to ascertain parameters to inform patients and physicians regarding the risk of ITVS and guide the clinical decision-making process of patients with severe TR, especially as transcatheter therapies are emerging (www.tri-score.com).

Isolated tricuspid valve surgery: impact of aetiology and clinical presentation on outcomes.

AIMS: The aim of this study was to identify determinants of in-hospital and mid-term outcomes after isolated tricuspid valve surgery (ITVS) and more specifically the impact of tricuspid regurgitation (TR) mechanism and clinical presentation. METHODS AND RESULTS: Among 5661 consecutive adult patients who underwent a tricuspid valve (TV) surgery at 12 French tertiary centres in 2007-2017 collected from a mandatory administrative database, we identified 466 patients (8% of all tricuspid surgeries) who underwent an ITVS. Most patients presented with advanced disease [47% in New York Heart Association (NYHA) III/IV, 57% with right-sided heart failure (HF) signs]. Tricuspid regurgitation was functional in 49% (22% with prior left-sided heart valve surgery and 27% isolated) and organic in 51% (infective endocarditis in 31% and other causes in 20%). In-hospital mortality and major complications rates were 10% and 31%, respectively. Rates of survival and survival free of HF readmission were 75% and 62% at 5 years. Patients with functional TR incurred a worse in-hospital mortality than those with organic TR (14% vs. 6%, P = 0.004), but presentation was more severe. Independent determinants of outcomes were NYHA Class III/IV [odd ratios (OR) = 2.7 (1.2-6.1), P = 0.01], moderate/severe right ventricular dysfunction [OR = 2.6 (1.2-5.8), P = 0.02], lower prothrombin time [OR = 0.98 (0.96-0.99), P = 0.008], and with borderline statistical significance, right-sided HF signs [OR = 2.4 (0.9-6.5), P = 0.06] while TR mechanism was not [OR = 0.7 (0.3-1.8), P = 0.88]. CONCLUSION: Isolated TV surgery was associated with high mortality and morbidity, both in hospital and during follow-up, predicted by the severity of the presentation but not by TR mechanism. Our results suggest that TV intervention should be performed earlier in the course of the disease.

Maternal Milk T Cells Drive Development of Transgenerational Th1 Immunity in Offspring Thymus.

Using multiple murine foster-nursing protocols, thereby eliminating placental transfer and allowing a distinction between dam- and pup-derived cells, we show that foster nursing by an immunized dam results in development of CD8(+) T cells in nonimmunized foster pups that are specific for Ags against which the foster dam was immunized (Mycobacterium tuberculosis or Candida albicans). We have dubbed this process "maternal educational immunity" to distinguish it from passive cellular immunity. Of the variety of maternal immune cells present in milk, only T cells were detected in pup tissues. Maternal T cells, a substantial percentage of which were CD4(+)MHC class II(+), accumulated in the pup thymus and spleen during the nursing period. Further analysis of maternal cells in the pup thymus showed that a proportion was positive for maternal immunogen-specific MHC class II tetramers. To determine the outcome of Ag presentation in the thymus, the maternal or foster pup origin of immunogen-responding CD8(+) cells in foster pup spleens was assessed. Whereas ∼10% were maternally derived in the first few weeks after weaning, all immunogen-responding CD8(+) T cells were pup derived by 12 wk of age. Pup-derived immunogen-responsive CD8(+) cells persisted until at least 1 y of age. Passive cellular immunity is well accepted and has been demonstrated in the human population. In this study, we show an arguably more important role for transferred immune cells: the direction of offspring T cell development. Harnessing maternal educational immunity through prepregnancy immunization programs has potential for improvement of infant immunity.

Increased use of brachiocephalic arteriovenous fistulas improves functional primary patency.

OBJECTIVE: As vascular surgeons strive to meet the Fistula First Initiative, some authors have observed a decrease in arteriovenous fistula (AVF) maturation rates in association with an increase in AVF creation. In May 2012, we adopted a practice change in an attempt to maintain the same high level of AVF creation while leading to a decrease in fistula failures. METHODS: A retrospective study was conducted of all dialysis access procedures performed by a single vascular surgeon before (period 1; before May 1, 2012) and after (period 2; after May 1, 2012) the change in practice pattern. The adopted change included favoring the brachiocephalic location unless the patient was an ideal anatomic candidate for a radiocephalic AVF, creating a larger and standardized arteriotomy, and using a large venous footplate whenever possible. The main outcome measure was primary functional patency at 1 year. Secondary outcome measures included primary patency at 1 year, time to maturation, type of fistula created, steal syndrome, and tunneled hemodialysis catheter infections. RESULTS: Of 213 vascular access procedures performed, 191 (90%) were AVFs. There was no difference in use of AVFs between period 1 (93% AVFs) and period 2 (88% AVFs; P = .2). Use of brachiocephalic AVFs increased from 38% in period 1 to 56% in period 2 (P = .01), with a corresponding trend toward a decrease in radiocephalic AVFs in period 2 (36% in period 1 to 27% in period 2; P = .2). Primary functional patency at 1 year was 47% in period 1 and 63% in period 2 (P = .03). Primary patency at 1 year was 51% in period 1 and 70% in period 2 (P = .001). Time to reach functional maturation was decreased in period 2 (median, 76 vs 82.5 days; P = .046). There was no difference in steal syndrome (P = 1.0), and the incidence of hemodialysis catheter infections was lower in period 2 (0 vs 7 [7%]; P = .006). CONCLUSIONS: Increasing brachiocephalic AVF creation and reducing our reliance on radiocephalic AVFs resulted in a significant increase in primary functional patency at 1 year. This was achieved while maintaining the same high percentage of fistulas, a lower rate of central catheter infections, and the same low incidence of steal syndrome.

Feasibility of percutaneous mitral commissurotomy in patients with commissural mitral valve calcification.

AIMS: Whether a percutaneous mitral commissurotomy (PMC) should be attempted in patients with mitral stenosis (MS) and valvular calcification, especially located at the commissural level remained debated. We sought to evaluate the impact of the degree and location of mitral valve calcifications on PMC results. METHODS AND RESULTS: Over a 3-year period, we enrolled 464 consecutive patients who underwent a PMC at our institution. According to the location (within the body valve leaflets' or at the commissural level) and the degree of calcification, patients were divided into three groups: 261 patients were in Group 1 (no leaflets' or commissural calcification), 141 in Group 2 (leaflets' calcification with no significant commissural calcification), and 62 in Group 3 (at least one commissure significantly calcified). Final valve area (1.83 ± 0.26, 1.71 ± 0.25, and 1.60 ± 0.24 cm(2), P < 0.00001) and the rate of complete opening of at least one commissure (92, 94, and 84%, P = 0.05) were significantly different. However, the rate of post-PMC mitral regurgitation (MR) of grade ≥ 3 (10, 10, and 8%, P = 0.90) was not different among the groups and if the rate of good immediate result, defined as valve area ≥ 1.5 cm(2) with no MR >2/4 was different among the three groups (88, 78, and 73%, P = 0.004), an overallprocedural success could be achieved in most patients with calcified commissures. CONCLUSION: In this large contemporary series of patients with MS, a procedural success was obtained less frequently in patients with calcified commissure but a successful PMC could still be safely achieved in a large proportion of patients. Our results support the use of PMC as a first-line treatment of patients with severe MS even in the presence of significant commissural calcifications with otherwise favourable clinical characteristics.

Impact of the coronavirus disease 2019 pandemic on aortic valve replacement and outcomes in France.

BACKGROUND: The coronavirus disease of 2019 (COVID-19) pandemic lockdowns limited access to medical care. The impact on surgical (SAVR) and transcatheter (TAVR) aortic valve replacement (AVR) has been poorly described. AIM: We sought to evaluate the impact of the COVID-19 pandemic on the number and modalities of AVR, patient demographics and in-hospital outcomes at the nationwide level. METHODS: Using the French nationwide administrative hospital discharge database, we compared projected numbers and proportions of AVR and hospital outcomes, obtained using linear regressions derived from 2015-2019 trends, with those observed in 2020. RESULTS: In 2020, 21,382 AVRs were performed (13,051 TAVRs, 5706 isolated SAVRs and 2625 SAVRs combined with other cardiac surgery). Compared with the 2020 projected number of AVRs (24,586, 95% confidence interval [CI] 23,525-25,646), TAVRs (14,866, 95% CI 14,164-15,568), isolated SAVRs (6652, 95% CI 6203-7100) and SAVRs combined with other cardiac surgery (3069, 95% CI 2822-3315), there were reductions of 13.0%, 12.2%, 14.2% and 14.5%, respectively. These trends were similar regardless of sex or age. In 2020, the mean age, Charlson Comorbidity Index and hospital admission duration continued to decline, and the proportion of females remained constant, following 2015-2019 trends. Overall, 2020 in-hospital mortality was higher than projected (2.0% observed vs. 1.7% projected; 95% CI 1.5-1.9%), with no increased pacemaker implantation, but more acute kidney injury and cerebrovascular accidents in some surgical subsets. CONCLUSIONS: During the COVID-19 pandemic, fewer TAVR and SAVR procedures were performed, with increased in-hospital mortality and periprocedural complications. Extended follow-up will be important to establish the long-term effect of the COVID-19 pandemic on patient management and outcomes.

Aortic valve replacement for aortic stenosis: Influence of centre volume on TAVR adoption rates and outcomes in France.

BACKGROUND: Transcatheter (TAVR) has supplanted surgical (SAVR) aortic valve replacement (AVR). AIM: To evaluate whether adoption of this technology has varied according to centre volume at the nationwide level. METHODS: From an administrative hospital-discharge database, we collected data on all AVRs performed in France between 2007 and 2019. Centres were divided into terciles based on the annual number of SAVRs performed in 2007-2009 ("before TAVR era"). RESULTS: A total of 192,773 AVRs (134,662 SAVRs and 58,111 TAVRs) were performed in 47 centres. The annual number of AVRs and TAVRs increased significantly and linearly in low-volume (<152 SAVRs/year; median 106, interquartile range [IQR] 75-129), middle-volume (152-219 SAVRs/year; median 197, IQR 172-212) and high-volume (>219 SAVRs/year; median 303, IQR 268-513) terciles, but to a greater degree in the latter (+14, +16 and +24 AVRs/centre/year and +16, +19 and +31 TAVRs/centre/year, respectively; PANCOVA<0.001). Charlson Comorbidity Index and in-hospital death rates declined from 2010 to 2019 in all terciles (all Ptrend<0.05). In 2017-2019, after adjusting for age, sex and Charlson Comorbidity Index, there was a trend toward lower death rates in the high-volume tercile (P=0.06) for SAVR, whereas death rates were similar for TAVR irrespective of tercile (P=0.27). Similar results were obtained when terciles were defined based on number of interventions performed in the last instead of the first 3years. Importantly, even centres in the lowest-volume tercile performed a relatively high number of interventions (150 TAVRs/year/centre). CONCLUSIONS: In a centralized public healthcare system, the total number of AVRs increased linearly between 2007 and 2019, mostly due to an increase in TAVR, irrespective of centre volume. Progressive declines in patient risk profiles and death rates were observed in all terciles; in 2017-2019 death rates were similar in all terciles, although lower in high-volume centres for SAVR.

Kuppfer cells trigger nonalcoholic steatohepatitis development in diet-induced mouse model through tumor necrosis factor-α production.

BACKGROUND: The mechanisms triggering nonalcoholic steatohepatitis (NASH) remain poorly defined. RESULTS: Kupffer cells are the first responding cells to hepatocyte injuries, leading to TNFα production, chemokine induction, and monocyte recruitment. The silencing of TNFα in myeloid cells reduces NASH progression. CONCLUSION: Increase of TNFα-producing Kupffer cells is crucial for triggering NASH via monocyte recruitment. SIGNIFICANCE: Myeloid cells-targeted silencing of TNFα might be a tenable therapeutic approach. Nonalcoholic steatohepatitis (NASH), characterized by lipid deposits within hepatocytes (steatosis), is associated with hepatic injury and inflammation and leads to the development of fibrosis, cirrhosis, and hepatocarcinoma. However, the pathogenic mechanism of NASH is not well understood. To determine the role of distinct innate myeloid subsets in the development of NASH, we examined the contribution of liver resident macrophages (i.e. Kupffer cells) and blood-derived monocytes in triggering liver inflammation and hepatic damage. Employing a murine model of NASH, we discovered a previously unappreciated role for TNFα and Kupffer cells in the initiation and progression of NASH. Sequential depletion of Kupffer cells reduced the incidence of liver injury, steatosis, and proinflammatory monocyte infiltration. Furthermore, our data show a differential contribution of Kupffer cells and blood monocytes during the development of NASH; Kupffer cells increased their production of TNFα, followed by infiltration of CD11b(int)Ly6C(hi) monocytes, 2 and 10 days, respectively, after starting the methionine/choline-deficient (MCD) diet. Importantly, targeted knockdown of TNFα expression in myeloid cells decreased the incidence of NASH development by decreasing steatosis, liver damage, monocyte infiltration, and the production of inflammatory chemokines. Our findings suggest that the increase of TNFα-producing Kupffer cells in the liver is crucial for the early phase of NASH development by promoting blood monocyte infiltration through the production of IP-10 and MCP-1.

Association of Age and Sex With Use of Transcatheter Aortic Valve Replacement in France.

BACKGROUND: Current guidelines recommend selecting surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) based on age, comorbidities, and surgical risk. Nevertheless, reports from the United States suggest a rapid expansion of TAVR in young patients. OBJECTIVES: The authors sought to evaluate the trends in TAVR uptake at a nationwide level in France according to age and sex. METHODS: Using a nationwide administrative database, we evaluated age- and sex-related trends in TAVR uptake, patient demographics, and in-hospital outcomes between 2015 and 2020. RESULTS: A total of 107,397 patients (44.0% female) underwent an isolated aortic valve replacement (AVR) (59.1% TAVR, 40.9% SAVR). In patients <65 years of age, the proportion of TAVR increased by 63.2% (P < 0.001) from 2015 to 2020 but remained uncommon at 11.1% of all AVR by 2020 (12.4% in females, 10.6% in males) while TAVR was the dominant modality in patients ≥65 years of age. In patients undergoing TAVR, the Charlson comorbidity index (CCI) (P = 0.119 for trend) and in-hospital mortality (P = 0.740 for trend) remained unchanged in patients <65 years of age but declined in those ≥65 years of age irrespective of sex (all P < 0.001 for trends). Females were older (P < 0.001), had lower CCI (P < 0.001), were more likely to undergo TAVR (P < 0.001), and experienced higher in-hospital mortality (TAVR, P = 0.015; SAVR, P < 0.001) that persisted despite adjustment for age and CCI. CONCLUSIONS: In France, the use of TAVR remained uncommon in young patients, predominantly restricted to those at high risk. Important sex differences were observed in patent demographics, selection of AVR modality, and patient outcomes. Additional research evaluating the long-term impact of TAVR use in young patients and prospective data evaluating sex differences in AVR modality selection and outcomes are needed.

Extracellular hepatitis C virus core protein activates STAT3 in human monocytes/macrophages/dendritic cells via an IL-6 autocrine pathway.

Hepatitis C virus (HCV) infection is highly efficient in the establishment of persistent infection, which leads to the development of chronic liver disease and hepatocellular carcinoma. Impaired T cell responses with reduced IFN-γ production have been reported to be associated with persistent HCV infection. Extracellular HCV core is a viral factor known to cause HCV-induced T cell impairment via its suppressive effect on the activation and induction of pro-inflammatory responses by antigen-presenting cells (APCs). The activation of STAT proteins has been reported to regulate the inflammatory responses and differentiation of APCs. To further characterize the molecular basis for the regulation of APC function by extracellular HCV core, we examined the ability of extracellular HCV core to activate STAT family members (STAT1, -2, -3, -5, and -6). In this study, we report the activation of STAT3 on human monocytes, macrophages, and dendritic cells following treatment with extracellular HCV core as well as treatment with a gC1qR agonistic monoclonal antibody. Importantly, HCV core-induced STAT3 activation is dependent on the activation of the PI3K/Akt pathway. In addition, the production of multifunctional cytokine IL-6 is essential for HCV core-induced STAT3 activation. These results suggest that HCV core-induced STAT3 activation plays a critical role in the alteration of inflammatory responses by APCs, leading to impaired anti-viral T cell responses during HCV infection.

Distribution of prolactin receptors suggests an intraductal role for prolactin in the mouse and human mammary gland, a finding supported by analysis of signaling in polarized monolayer cultures.

Despite the important role of prolactin (PRL) in mammary gland development and function, little is known about the distribution of the different forms of the prolactin receptor (PRLR) under various physiological circumstances. Here, the distribution of the long (LF) and the short (S3 in mouse) receptor common to both mice and rats was determined by immunofluorescence on frozen sections of virgin, pregnant and lactating mouse mammary gland. Myoepithelial cells were consistently and intensely stained for both receptors. For luminal cells at all stages (ducts and alveoli), a large proportion of PRLR staining was unexpectedly present on the apical face. In the non-lactating state, no basal staining of luminal cells was detectable. During lactation, a proportion of both receptors moved to the basolateral surface. In vitro, HC11 cells showed constitutive expression of LF but expression of S3 only upon the formation of adherent junctions. Tight junction formation was accelerated by incubation in pseudo-phosphorylated PRL, as measured by transepithelial resistance and the expression and placement of the tight junction protein, zonula occludens-1. Once an intact monolayer had formed, all LF and S3 receptors were apical (akin to the non-lactating state) and only apical application of PRL activated the Jak2-STAT5 and ERK pathways. By contrast, basolateral application of PRL resulted in a reduction in basal ERK phosphorylation, suggesting an involvement of a dual specificity protein phosphatase. Normal human breast samples also showed apical PRLRs. These results demonstrate important contextual aspects of PRL-PRLR interactions with implications for the analysis of the role of PRL in breast cancer.

The "50% rule" in arthroscopic and orthopaedic surgery.

The "50% rule" is used commonly to guide treatment of partial tears of tendons and ligaments. The purpose of this study was to examine the history and validity of the 50% rule in arthroscopic and orthopaedic surgery. A PubMed search yielded 1,039 articles that were reviewed to identify the origins of the 50% rule for hand flexor tendon lacerations, partial anterior cruciate ligament tears, partial-thickness rotator cuff tears, and partial injuries of the long head of the biceps tendon. The rule appears to have evolved from the hand literature toward somewhat arbitrary application for other orthopaedic conditions. Little scientific information is available to support the 50% rule for these disparate entities. In our Level V opinion, the 50% rule allows surgeons to use subjective discretion in the management of prevalent orthopaedic conditions but there is very little scientific support for this ubiquitous decision-making criterion.

Size-adjusted aortic valve area: refining the definition of severe aortic stenosis.

AIMS: Severe aortic valve stenosis (AS) is defined by an aortic valve area (AVA) <1 cm2 or an AVA indexed to body surface area (BSA) <0.6 cm/m2, despite little evidence supporting the latter approach and important intrinsic limitations of BSA indexation. We hypothesized that AVA indexed to height (H) might be more applicable to a wide range of populations and body morphologies and might provide a better predictive accuracy. METHODS AND RESULTS: In 1298 patients with degenerative AS and preserved ejection fraction from three different countries and continents (derivation cohort), we aimed to establish an AVA/H threshold that would be equivalent to 1.0 cm2 for defining severe AS. In a distinct prospective validation cohort of 395 patients, we compared the predictive accuracy of AVA/BSA and AVA/H. Correlations between AVA and AVA/BSA or AVA/H were excellent (all R2 > 0.79) but greater with AVA/H. Regressions lines were markedly different in obese and non-obese patients with AVA/BSA (P < 0.0001) but almost identical with AVA/H (P = 0.16). AVA/BSA values that corresponded to an AVA of 1.0 cm2 were markedly different in obese and non-obese patients (0.48 and 0.59 cm2/m2) but not with AVA/H (0.61 cm2/m for both). Agreement for the diagnosis of severe AS (AVA < 1 cm2) was significantly higher with AVA/H than with AVA/BSA (P < 0.05). Similar results were observed across the three countries. An AVA/H cut-off value of 0.6 cm2/m [HR = 8.2(5.6-12.1)] provided the best predictive value for the occurrence of AS-related events [absolute AVA of 1 cm2: HR = 7.3(5.0-10.7); AVA/BSA of 0.6 cm2/m2 HR = 6.7(4.4-10.0)]. CONCLUSION: In a large multinational/multiracial cohort, AVA/H was better correlated with AVA than AVA/BSA and a cut-off value of 0.6 cm2/m provided a better diagnostic and prognostic value than 0.6 cm2/m2. Our results suggest that severe AS should be defined as an AVA < 1 cm2 or an AVA/H < 0.6 cm2/m rather than a BSA-indexed value of 0.6 cm2/m2.

Hypotony maculopathy after eyelid massage for overcorrected blepharoptosis.

A 57-year-old woman with a history of left eye trabeculectomy was evaluated for gradual ipsilateral visual loss. Several months prior, she had undergone levator advancement of the left upper eyelid. For management of resulting retraction, she was instructed to "massage" her eyelid. Examination was notable for left eye visual acuity of 20/200 and an intraocular pressure of 5 mm Hg. On fundoscopic examination, the macula was edematous with multiple folds, consistent with hypotony maculopathy. Two years later, after obliteration of the bleb and placement of a Seton valve, the intraocular pressure has increased to 8 mm Hg with an acuity correctable to 20/50. Ocular hypotony may result from digital eyelid massage in patients with filtering blebs. Clinicians should bear this in mind when managing patients with eyelid retraction after blepharoptosis repair.

Epicardial adipose tissue volume is associated with left ventricular remodelling in calcific aortic valve stenosis.

BACKGROUND: The severity of left ventricular (LV) remodelling is only partially related to the severity of aortic valve stenosis; additional factors, including diabetes, insulin resistance, obesity and metabolic syndrome, may play important roles. Epicardial adipose tissue (EAT), now considered as a metabolically active organ, is also linked to these factors. AIM: To analyse the association between EAT volume measured using computed tomography and LV remodelling in a prospective cohort of patients with aortic stenosis. METHODS: Consecutive asymptomatic patients with at least mild degenerative aortic stenosis enrolled in a prospective cohort that aimed to assess the determinants of aortic stenosis occurrence and progression constituted our population. RESULTS: We enrolled 143 patients (78±5 years; 65% men). Mean LV mass and EAT volume were 219±64g and 134±56mL, respectively. LV hypertrophy was diagnosed in 86 patients (60%), and concentric hypertrophy (32%) was the main remodelling pattern. EAT was associated with body mass index (P<0.001) and body surface area (P<0.001), but not with age (P=0.33) or aortic stenosis severity (all P>0.10). EAT was correlated with LV mass (r=0.41; P<0.0001), and after adjustment for age, sex, body mass index/body surface area, hypertension, waist circumference, low-density lipoprotein cholesterol and aortic stenosis severity, EAT was independently associated with LV mass (P=0.01/P=0.02). Similar results were found when EAT and LV mass index (adjusted for body surface area) were considered instead of absolute values (P=0.04). CONCLUSIONS: In this prospective cohort of patients with aortic stenosis, EAT volume was independently associated with LV mass. Further studies are warranted to elucidate the underlying mechanisms of this link.

Ascending aorta dilatation rates in patients with tricuspid and bicuspid aortic stenosis: the COFRASA/GENERAC study.

Background: Ascending aorta (AA) dilatation is common in aortic valve stenosis (AS) but data regarding AA progression, its determinants and impact of valve anatomy [bicuspid (BAV), or tricuspid (TAV)] are scarce. Methods and Results: Asymptomatic AS patients enrolled in a prospective cohort (COFRASA/GENERAC) with at least 2 years of follow-up were considered in the present analysis. A transthoracic echocardiography (TTE) and a computed tomography (CT) scan were performed at inclusion and yearly thereafter. We enrolled 195 patients [mean gradient 22 ± 11 mmHg, 42 BAV patients (22%)]. Mean aorta diameters assessed using TTE were 35 ± 4 and 36 ± 5 mm at the sinuses of Valsalva and tubular level, respectively. Ascending aorta diameter was >40 mm in 29% of patients (24% in TAV vs. 52% in BAV, P < 0.01). Determinants of AA diameters were age, sex, BSA, and BAV, but not AS severity. After a mean follow-up of 3.8 ± 1.5years, AA enlargement rate assessed using TTE was +0.18 ± 0.34 mm/year and +0.36 ± 0.54 mm/year at the Valsalva and tubular level, respectively. Determinants of the progression of AA size were smaller AA diameter (P < 0.01) but not baseline AS severity or valve anatomy (all P > 0.05). Only four patients presented an AA progression ≥2 mm/year. Correlations between TTE and CT scan were excellent (all r >0.74) and similar results were obtained using CT. During follow-up, two BAV patients underwent a combined AA surgery; no surgery was primarily performed for AA aneurysm and no dissection was observed. Conclusion: In this prospective cohort of AS patients determinants of AA diameters were age, sex, BSA, and valve anatomy but not AS severity. AA progression rates were low and not influenced by AS severity or valve anatomy.

Implementation of Transcatheter Aortic Valve Replacement in France.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has emerged as an alternative to surgical aortic valve replacement (SAVR), but unbiased data regarding evolution of the treatment of patients with aortic stenosis at the nationwide level are scarce. OBJECTIVES: This study sought to evaluate the number of aortic valve replacements (AVRs) performed in France, changes over time, and the effect of the adoption of TAVR. METHODS: Based on a French administrative hospital-discharge database, the study collected all consecutive AVRs performed in France between 2007 and 2015. RESULTS: A total of 131,251 interventions were performed: 109,317 (83%) SAVR and 21,934 (17%) TAVR. AVR linearly increased (from 10,892 to 18,704; p for trend <0.0001) mainly due to a marked increase in TAVR (from 244 to 6,722; p for trend = 0.0004), whereas SAVR remained stable (from 10,892 to 11,982; p for trend = 0.18). Parallel to a decrease in the Charlson index (p for trend <0.05), SAVR and TAVR in-hospital mortality rates significantly declined (both p for trend <0.01). The number of TAVRs significantly increased in all age categories (<75, 75 to 79, 80 to 84, and ≥85 years of age; all p for trend = 0.003), but reached or even exceeded SAVR in the 2 oldest categories. Although mortality rates declined for both isolated SAVR and TAVR, it became similar or slightly lower for TAVR than for isolated SAVR in 2015 in the 3 oldest age categories even if it did not reach statistical significance (p = 0.66, p = 0.47, and p = 0.06, respectively). CONCLUSIONS: The number of AVRs markedly increased in France between 2007 and 2015 due to the wide adoption of TAVR, which represented one-third of all AVRs in 2015. Patients' profile improved, suggesting that patients are referred earlier, and in-hospital mortality declined in all AVR subsets. Despite a worse clinical profile, the immediate outcome of TAVR compared favorably to isolated SAVR in patients >75 years of age. The results may have major implications for clinical practice and policymakers.