Prevention and Mitigation of Heart Failure in the Treatment of Calcific Aortic Stenosis

2021 ◽  
Author(s):  
Brian R. Lindman ◽  
JoAnn Lindenfeld
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.


Circulation ◽  
1995 ◽  
Vol 92 (10) ◽  
pp. 3138-3138
Author(s):  
Richard L. Mueller ◽  
Geoffrey Bergman

1958 ◽  
Vol 36 (6) ◽  
pp. 759-776 ◽  
Author(s):  
Dwight E. Harken ◽  
Harrison Black ◽  
Warren J. Taylor ◽  
Wendell B. Thrower ◽  
Harry S. Soroff

2021 ◽  
Vol 77 (18) ◽  
pp. 1703
Author(s):  
Mika Maeda ◽  
Shunsuke Kagawa ◽  
Taku Omori ◽  
Goki Uno ◽  
Shunsuke Shimada ◽  
...  

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Piayda ◽  
A Wimmer ◽  
H Sievert ◽  
K Hellhammer ◽  
S Afzal ◽  
...  

Abstract Background In the era of transcatheter aortic valve replacement (TAVR), there is renewed interest in percutaneous balloon aortic valvuloplasty (BAV), which may qualify as the primary treatment option of choice in special clinical situations. Success of BAV is commonly defined as a significant mean pressure gradient reduction after the procedure. Purpose To evaluate the correlation of the mean pressure gradient reduction and increase in the aortic valve area (AVA) in different flow and gradient patterns of severe aortic stenosis (AS). Methods Consecutive patients from 01/2010 to 03/2018 undergoing BAV were divided into normal-flow high-gradient (NFHG), low-flow low-gradient (LFLG) and paradoxical low-flow low-gradient (pLFLG) AS. Baseline characteristics, hemodynamic and clinical information were collected and compared. Additionally, the clinical pathway of patients (BAV as a stand-alone procedure or BAV as a bridge to aortic valve replacement) was followed-up. Results One-hundred-fifty-six patients were grouped into NFHG (n=68, 43.5%), LFLG (n=68, 43.5%) and pLFLG (n=20, 12.8%) AS. Underlying reasons for BAV and not TAVR/SAVR as the primary treatment option are displayed in Figure 1. Spearman correlation revealed that the mean pressure gradient reduction had a moderate correlation with the increase in the AVA in patients with NFHG AS (r: 0.529, p<0.001) but showed no association in patients with LFLG (r: 0.145, p=0.239) and pLFLG (r: 0.030, p=0.889) AS. Underlying reasons for patients to undergo BAV and not TAVR/SAVR varied between groups, however cardiogenic shock or refractory heart failure (overall 46.8%) were the most common ones. After the procedure, independent of the hemodynamic AS entity, patients showed a functional improvement, represented by substantially lower NYHA class levels (p<0.001), lower NT-pro BNP levels (p=0.003) and a numerical but non-significant improvement in other echocardiographic parameters like the left ventricular ejection fraction (p=0.163) and tricuspid annular plane systolic excursion (TAPSE, p=0.066). An unplanned cardiac re-admission due to heart failure was necessary in 23.7% patients. Less than half of the patients (44.2%) received BAV as a bridge to TAVR/SAVR (median time to bridge 64 days). Survival was significantly increased in patients having BAV as a staged procedure (log-rank p<0.001). Conclusion In daily clinical practice, the mean pressure gradient reduction might be an adequate surrogate of BAV success in patients with NFHG AS but is not suitable for patients with other hemodynamic entities of AS. In those patients, TTE should be directly performed in the catheter laboratory to correctly assess the increase of the AVA. BAV as a staged procedure in selected clinical scenarios increases survival and is a considerable option in all flow states of severe AS. (NCT04053192) Figure 1 Funding Acknowledgement Type of funding source: None


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