Flyer JN, Sleeper LA, Colan SD, Singh MN, Lacro RV.
Am J Cardiol. 2020 Dec 29:S0002-9149(20)31400-4. doi: 10.1016/j.amjcard.2020.12.050. Online ahead of print.
PMID: 33383013
Take Home Points:
In children and young adults with bicuspid aortic valve and dilated ascending aorta, in this retrospective, single centre, non-placebo controlled, non-blinded and non-randomised study of 41 patients:
- Treatment with losartan or atenolol over an average three year period reduced aortic root and ascending aorta Z-scores.
- Both resulted in an apparent reduction in absolute aortic diameter growth rates.
- Losartan or atenolol may reduce proximal aortic growth rates in young patients with bicuspid valve aortic aortopathy.
Commentary from Dr Simon MacDonald (London, UK), section editor of ACHD Journal Watch: It is established that beta-blockade and angiotensin II blockade protects against aortic dilatation in Marfan’s syndrome but their role and possible effectiveness in other types of aortopathy is unclear. The authors studied whether atenolol or losartan prophylaxis reduces aortic dilatation in children and young adults with bicuspid aortic valve and dilated ascending aorta. In this group, severe dilatation is associated with risk of dissection and death.
They reviewed patients with bicuspid aortic valve and aortic dilatation (aged 1 day to 29 years) at Boston Children’s Hospital over the time period 1990-2018. Their hospital protocol recommended medical prophylaxis with losartan or atenolol for patients with bicuspid aortic valve and severe aortic root or ascending aorta dilatation. Patients were identified via their hospital database with BAV and aortic root or ascending aorta diameter with z-score ≥ 4SD and/or absolute diameter ≥ 4cm, and history of prophylaxis with losartan or atenolol. Patients with other congenital heart disease, apart from coarctation, or known connective tissue disorders were excluded.
The primary outcome analysed was the annual rate of change in maximal aortic root and ascending aorta z-scores (SD/yr) compared with those before treatment. Mean changes over time in aortic diameter and BSA adjusted z-scores for the treatments were analysed using a mixed effects linear regression model.
They included gender as a subgroup, in addition to age at initiation (<15 yrs. and ≥ 15years), aortic z-score, coarctation surgery, presence or absence of moderate aortic insufficiency or stenosis. Forty-one patients were included in the analysis, 27 in the losartan group and 18 in the atenolol (4 patients included in both groups as received each drug at different times) with similar baseline characteristics (Table 1A). Median treatment duration was 3.1 years for losartan (IQR 2.4, 6.0) and 3.7 for atenolol (IQR 1.4,6.6) with mean age of initiation of therapy 14.2±5.1 and 15±4.9 years respectively.
Treatment was associated with decreases in aortic root and ascending aorta z-scores (SD/yr) for losartan and atenolol (pre- vs post-treatment) with:
Losartan, n=27:
Aortic root: +0.06± 0.02 pre vs -0.14±0.03 post, p<0.001
Ascending aorta: +0.2±0.03 pre vs -0.09±0.05 post, p<0.001
Atenolol, n=18:
Aortic root: +0.07±0.03 pre vs -0.02±0.04 post, p<0.01
Ascending aorta: +0.21±0.04 pre vs -0.06±0.006, p<0.001
There was a decrease in absolute growth rate (cm/year) for all comparisons (p≤0.02) too.
There were no deaths, with four patients in the losartan group and five in the atenolol having surgery. This was for Sinus of Valsalva fistula (1), aortic size (2), and progressive aortic regurgitation (6). Seven had aortic valve repair/replacement and 8 had replacement/reduction of the aortic root and or ascending aorta.
Patients were not randomised, it was a single centre retrospective study, variable drug dosing, and unblinded echo assessment were potential limitations. In terms of subgroup analysis, there were a small number of patients assessed, and coarctation surgery, aortic valve dysfunction and timing of growth spurts in male/female patients were potential confounders. The authors conclude that additional large clinical studies are warranted with these medications to confirm possible effect and help decrease the rate of serious aortic events during adulthood.
