scholarly journals 142Insulin resistance, left ventricular hypertrophy and the impact of metformin use on cardiovascular outcomes in patients with calcific aortic stenosis: a genetic and population cohort study

2018 ◽  
Vol 39 (suppl_1) ◽  
Author(s):  
I Mordi ◽  
D Levin ◽  
A Aracil ◽  
M Mohan ◽  
J Singh ◽  
...  
2009 ◽  
Vol 297 (1) ◽  
pp. H65-H75 ◽  
Author(s):  
Cordelia J. Barrick ◽  
Reade B. Roberts ◽  
Mauricio Rojas ◽  
Nalini M. Rajamannan ◽  
Carolyn B. Suitt ◽  
...  

Epidermal growth factor receptor (EGFR) signaling contributes to aortic valve development in mice. Because developmental phenotypes in Egfr-null mice are dependent on genetic background, the hypomorphic Egfr wa2 allele was made congenic on C57BL/6J (B6) and 129S1/SvImJ (129) backgrounds and used to identify the underlying cellular cause of EGFR-related aortic valve abnormalities. Egfr wa2/wa2 mice on both genetic backgrounds develop aortic valve hyperplasia. Many B6- Egfr wa2/wa2 mice die before weaning, and those surviving to 3 mo of age or older develop severe left ventricular hypertrophy and heart failure. The cardiac phenotype was accompanied by significantly thicker aortic cusps and larger transvalvular gradients in B6- Egfr wa2/wa2 mice compared with heterozygous controls and age-matched Egfr wa2 homozygous mice on either 129 or B6129F1 backgrounds. Histological analysis revealed cellular changes in B6- Egfr wa2/wa2 aortic valves underlying elevated pressure gradients and progression to heart failure, including increased cellular proliferation, ectopic cartilage formation, extensive calcification, and inflammatory infiltrate, mimicking changes seen in human calcific aortic stenosis. Despite having congenitally enlarged valves, 129 and B6129F1- Egfr wa2/wa2 mice have normal lifespans, absence of left ventricular hypertrophy, and normal systolic function. These results show the requirement of EGFR activity for normal valvulogenesis and demonstrate that dominantly acting genetic modifiers curtail pathological changes in congenitally deformed valves. These studies provide a novel model of aortic sclerosis and stenosis and suggest that long-term inhibition of EGFR signaling for cancer therapy may have unexpected consequences on aortic valves in susceptible individuals.


2012 ◽  
Vol 13 (13) ◽  
pp. 2503-2514 ◽  
Author(s):  
Cristina Gavina ◽  
Ines Falcao-Pires ◽  
Francisco Rocha-Goncalves ◽  
Adelino Leite-Moreira

2021 ◽  
Vol 10 (13) ◽  
pp. 2864
Author(s):  
Aleksandra Gamrat ◽  
Katarzyna Trojanowicz ◽  
Michał A. Surdacki ◽  
Aleksandra Budkiewicz ◽  
Adrianna Wąsińska ◽  
...  

Traditional electrocardiographic (ECG) criteria for left ventricular hypertrophy (LVH), introduced in the pre-echocardiographic era of diagnosis, have a relatively low sensitivity (usually not exceeding 25–40%) in detecting LVH. A novel Peguero-Lo Presti ECG-LVH criterion was recently shown to exhibit a higher sensitivity than the traditional ECG-LVH criteria in hypertension. Our aim was to test the diagnostic ability of the novel Peguero-Lo Presti ECG-LVH criterion in severe aortic stenosis. We retrospectively analyzed 12-lead ECG tracings and echocardiographic records from the index hospitalization of 50 patients with isolated severe aortic stenosis (mean age: 77 ± 10 years; 30 women and 20 men). Exclusion criteria included QRS > 120 ms, bundle branch blocks or left anterior fascicular block, a history of myocardial infarction, more than mild aortic or mitral regurgitation, and significant LV dysfunction by echocardiography. We compared the agreement of the novel Peguero-Lo Presti criterion and traditional ECG-LVH criteria with echocardiographic LVH (LV mass index > 95 g/m2 in women and >115 g/m2 in men). Echocardiographic LVH was found in 32 out of 50 study patients. The sensitivity of the Peguero-Lo Presti criterion in detecting LVH was improved (55% vs. 9–34%) at lower specificity (72% vs. 78–100%) in comparison to 8 single traditional ECG-LVH criteria. Additionally, the positive predictive value (77% vs. 72%), positive likelihood ratio (2.0 vs. 1.5), and odds ratio (3.2 vs. 2.4) were higher for the Peguero-Lo Presti criterion versus the presence of any of these 8 traditional ECG-LVH criteria. Cohen’s Kappa, a measure of concordance between ECG and echocardiography with regard to LVH, was 0.24 for the Peguero-Lo Presti criterion, −0.01–0.13 for single traditional criteria, and 0.20 for any traditional criterion. However, by the receiver operating characteristics (ROC) curve analysis, the overall ability to discriminate between patients with and without LVH was insignificantly lower for the Peguero-Lo Presti versus Cornell voltage as a continuous variable (area under the ROC curve: 0.65 (95% CI, 0.48–0.81) vs. 0.71 (0.55–0.86), p = 0.5). In conclusion, our preliminary results suggest a slightly better, albeit still low, agreement of the novel Peguero-Lo Presti ECG criterion compared to the traditional ECG-LVH criteria with echocardiographic LVH in severe aortic stenosis.


2013 ◽  
Vol 34 (suppl 1) ◽  
pp. P277-P277
Author(s):  
G. Barone-Rochette ◽  
S. Pierard ◽  
S. Seldrum ◽  
C. De Meester De Ravensteen ◽  
J. Melchior ◽  
...  

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