Publications by authors named "Tomer D Mann"

2 Publications

  • Page 1 of 1

Natural History of Moderate Aortic Stenosis with Preserved and Low Ejection Fraction.

J Am Soc Echocardiogr 2021 Feb 27. Epub 2021 Feb 27.

Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Tel Aviv Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address:

Background: There is a shortage of data concerning the natural history of patients with moderate aortic stenosis (AS). The aim of this study was to assess the effect of moderate AS on mortality in the general population and in the subgroups of patients with moderate AS and reduced ejection fractions (EF) and patients with moderate AS and low aortic valve gradients. The study was not designed to address the applicability of treatment in this population.

Methods: Outcomes were compared between patients with moderate AS and a propensity-matched cohort (1:3 ratio) without AS. The primary outcome was survival until end of follow-up.

Results: Among approximately 40,000 patients who underwent echocardiographic evaluations between 2011 and 2016, 952 had moderate AS. Median follow-up duration was 181 weeks (interquartile range, 179-182 weeks) for the entire cohort and 174 weeks (interquartile range, 169-179 weeks) for the propensity-matched groups. Propensity matching successfully balanced most preexisting clinical differences. Increased mortality was observed in the group of patients with moderate AS before propensity matching and persisted following propensity matching (median survival 4.1 vs 5.2 years, P = .008). Survival rates and corresponding standard errors at 1, 2, 3, and 5 years were 80 ± 1% versus 82 ± 0.7%, 70 ± 1.5% versus 74 ± 0.8%, 62 ± 1.7% versus 66 ± 0.9%, and 47 ± 2.4% versus 52 ± 1.3%, respectively. A survival difference was similarly observed for the subgroup analyses of moderate AS and reduced ejection fraction (P = .028) and moderate AS and low aortic valve gradients (P = .039).

Conclusions: Moderate AS is associated with increased mortality. The increased mortality was also observed in the subgroups of patients with either reduced ejection fraction or low aortic valve gradients.
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February 2021

RNA editing of Filamin A pre-mRNA regulates vascular contraction and diastolic blood pressure.

EMBO J 2018 10 7;37(19). Epub 2018 Aug 7.

Division of Cell Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria

Epitranscriptomic events such as adenosine-to-inosine (A-to-I) RNA editing by ADAR can recode mRNAs to translate novel proteins. Editing of the mRNA that encodes actin crosslinking protein Filamin A (FLNA) mediates a Q-to-R transition in the interactive C-terminal region. While FLNA editing is conserved among vertebrates, its physiological function remains unclear. Here, we show that cardiovascular tissues in humans and mice show massive editing and that FLNA RNA is the most prominent substrate. Patient-derived RNA-Seq data demonstrate a significant drop in FLNA editing associated with cardiovascular diseases. Using mice with only impaired FLNA editing, we observed increased vascular contraction and diastolic hypertension accompanied by increased myosin light chain phosphorylation, arterial remodeling, and left ventricular wall thickening, which eventually causes cardiac remodeling and reduced systolic output. These results demonstrate a causal relationship between RNA editing and the development of cardiovascular disease indicating that a single epitranscriptomic RNA modification can maintain cardiovascular health.
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October 2018