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Background: Dialysis is a rare but serious complication after transcatheter aortic valve replacement. We analyzed the large multicenter TRITAVI (transfusion requirements in transcatheter aortic valve implantation) registry in order to develop and validate a clinical score assessing this risk., Methods and Results: A total of 10 071 consecutive patients were enrolled in 19 European centers. Patients were randomly assigned (2:1) to a derivation and validation cohort. Two scores were developed, 1 including only preprocedural variables (TRITAVIpre) and 1 also including procedural variables (TRITAVIpost). In the 6714 patients of the derivation cohort (age 82±6 years, 48% men), preprocedural factors independently associated with dialysis and included in the TRITAVIpre score were male sex, diabetes, prior coronary artery bypass graft, anemia, nonfemoral access, and creatinine clearance <30 mL/min per m 2 . Additional independent predictors among procedural features were volume of contrast, need for transfusion, and major vascular complications. Both scores showed a good discrimination power for identifying risk for dialysis with C-statistic 0.78 for TRITAVIpre and C-statistic 0.88 for TRITAVIpost score. Need for dialysis increased from the lowest to the highest of 3 risk score groups (from 0.3% to 3.9% for TRITAVIpre score and from 0.1% to 6.2% for TRITAVIpost score). Analysis of the 3357 patients of the validation cohort (age 82±7 years, 48% men) confirmed the good discrimination power of both scores (C-statistic 0.80 for TRITAVIpre and 0.81 for TRITAVIpost score). Need for dialysis was associated with a significant increase in 1-year mortality (from 6.9% to 54.4%; P =0.0001)., Conclusions: A simple preprocedural clinical score can help predict the risk of dialysis after transcatheter aortic valve replacement.

DNA damage is emerging as a driver of heart disease, although the cascade of events, its timing, and the cell types involved are yet to be fully clarified. In this context, the implication of cardiomyocytes has been highlighted, while that of vasculature smooth muscle cells has been implicated but not explored exhaustively. In our previous work we characterized a factor called Ft1 in mice and AKTIP in humans whose depletion generates telomere instability and DNA damage. Herein, we explored the effect of the reduction of Ft1 on the heart with the goal of comparatively defining the impact of DNA damage targeted to vasculature smooth muscle cells to that of diffuse damage. Using two newly generated mouse models, Ft1 constitutively knocked out (Ft1ko) mice, and mice in which we targeted the Ft1 depletion to the smooth muscle cells (Ft1sm22ko), it is shown that both genetic models display cardiac defects but with differences. Both Ft1ko and Ft1sm22ko mice display hypertrophy, fibrosis, and functional heart defects. Interestingly, Ft1sm22ko mice have early milder pathological traits that become manifest with age. Significantly, the defects of Ft1ko mice, including the alteration of the left ventricle and functional heart defects, are rescued by depletion of the DNA damage sensor p53. These results point to Ft1 deficiency as a driver of cardiac disease and show that Ft1 deficiency targeted to vasculature smooth muscle cells generates a pre-pathological profile exacerbated by age., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Human AKTIP and mouse Ft1 are orthologous ubiquitin E2 variant proteins involved in telomere maintenance and DNA replication. AKTIP also interacts with A- and B-type lamins. These features suggest that Ft1 may be implicated in aging regulatory pathways. Here, we show that cells derived from hypomorph Ft1 mutant (Ft1 kof/kof ) mice exhibit telomeric defects and that Ft1 kof/kof animals develop progeroid traits, including impaired growth, skeletal and skin defects, abnormal heart tissue, and sterility. We also demonstrate a genetic interaction between Ft1 and p53. The analysis of mice carrying mutations in both Ft1 and p53 (Ft1 kof/kof ; p53 ko/ko and Ft1 kof/kof ; p53 +/ko ) showed that reduction in p53 rescues the progeroid traits of Ft1 mutants, suggesting that they are at least in part caused by a p53-dependent DNA damage response. Conversely, Ft1 reduction alters lymphomagenesis in p53 mutant mice. These results identify Ft1 as a new player in the aging process and open the way to the analysis of its interactions with other progeria genes using the mouse model., (© 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Objective: This study aims to assess changes in mitral regurgitation (MR) severity after transcatheter aortic valve implantation (TAVI)., Background: Existing data on MR after TAVI are contradictory., Methods: Thirty-five patients with MR graded ≥ 2+ were followed after undergoing TAVI with either the Edwards Sapien or CoreValve device. Echocardiography was performed the week before and 3 months after the procedure. MR was graded on a scale of 0 to 4+, classified as organic or functional, and the effective regurgitant orifice area (EROA) and MR index were calculated., Results: At baseline, MR was graded 4+ in 4 (11.4%) patients, 3+  in 10 (28.6%), and 2+ in 21 (60%). At follow-up, MR was graded at 3+ in 4 (11.4%) patients, 2+ in 8 (22.9%), and 1+ in 19 (54.3%); 4 (11.4%) exhibited no MR. EROA (24.4 ± 11.5 mm(2) pre-TAVI vs. 11.2 ± 10.3 mm(2) post-TAVI, P < 0.001) and MR index (1.9 ± 0.3 pre-TAVI vs. 1.3 ± 0.7 post-TAVI, P < 0.001) were reduced with TAVI, independent of the etiology. MR decreased by at least 1 grade in 28 (80%) patients, with a reduction ≥2 grades in 10 (28.6%) patients; no patient showed a worsened condition. Subgroup analyses showed that the reduction in MR was significant in patients treated with the Edwards Sapien device but not in patients treated with the CoreValve device., Conclusions: This multiparametric echocardiographic evaluation showed that MR improved significantly after TAVI and that this result may be related to the type of valve implanted., (© 2012, Wiley Periodicals, Inc.)

Problem: In consideration of the effect of adenosine deaminase (ADA) and ACP1 (a low-molecular-weight protein tyrosine phosphatase) on T-cell receptor activity, we have analysed the joint distribution of these polymorphisms in a sample of women with primary repeated spontaneous abortion (RSA) to search for possible interactive effects on susceptibility to RSA., Method of Study: ACP1 and ADA phenotypes were determined in 170 women with primary RSA in 79 healthy consecutive puerperae and in 160 female newborns from the Caucasian population of Rome and in 357 healthy consecutive puerperae from the Caucasian population of Penne. Chi-square test of independence and three way contingency table analysis by a log-linear model were performed., Results: Women with low-ADA activity and high-ACP1 activity show the lowest susceptibility to RSA. Women with high-ADA activity and low-ACP1 activity, on the contrary, show the highest susceptibility to RSA and also the highest incidence of auto antibodies and of A blood group incompatibility., Conclusion: The data are in agreement with those expected on the basis of the effects of ACP1 and ADA genetic variability on T-cell receptor activity and suggest a cooperative effect of the two polymorphic systems in the susceptibility/resistance to repeated spontaneous abortion.

A deviation of the maternal-neonatal joint phosphoglucomutase locus 1 (PGM1) distribution from Hardy-Weinberg expectation has been reported. It was suggested that selection on PGM1 during intrauterine life might account for these deviations and that maternal and paternal PGM1 alleles might have different associations with intrauterine survival. This study considered possible associations between the joint mother-newborn PGM1 genotype and intrauterine growth. There was a significant association between birth weight percentile class and mother-newborn PGM1 genotype in infant females. Also, the paternal PGM1*2 allele was associated negatively with macrosomia, and this effect was significant only in female infants.

An association of the phosphoglucomutase locus 1 (PGM1) genetic polymorphism with repeated spontaneous abortion (RSA), with intrauterine development in both normal and diabetic pregnancies, and with fertility has been reported in previous studies. In view of the evolutionary interest and of a possible clinical relevance of PGM1 selection during intrauterine life, this study considers healthy puerperae, consecutive newborns, and couples with RSA as well as two alleles (PGM1*1 and PGM1*2). The joint maternal-neonatal PGM1 distribution in a sample from an Italian rural population is significantly different from that expected assuming Hardy-Weinberg conditions for equilibrium. Deviation is dependent on maternal age and parity. The joint mother-newborn PGM1 genotype distribution is significantly associated with a positive history of previous spontaneous miscarriage, suggesting that the presence of the PGM1*2 allele in the father predisposes to spontaneous abortion. This hypothesis is also supported by the observation that in couples with RSA, the delivery of a live born infant within 5 years from the first episode of miscarriage is negatively associated with the presence of a PGM1*2 allele in the husband. Altogether these observations suggest the hypothesis of PGM1 maternal selection at the reproductive level involving a differential role of PGM1*1 and PGM1*2 alleles of paternal origin.