![Show Menu](styles/mobile-menu.png)
![Page Background](./../common/page-substrates/page0020.png)
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 31, No 3, May/June 2020
128
AFRICA
study, decreased E
′
velocity and increased ejection time and
isovolumetric relaxation time derived from the septal mitral
annulus may indicate a subclinical systolic dysfunction of both
ventricles.
Despite the significant differences in these parameters
between the three groups, we demonstrated a statistically
significant difference of only E velocity of RV inflow values in
the comparison between the IVA and LPC groups. Therefore
it is also possible that diastolic impairment may be due to
retinopathy-related co-morbidities in the treatment groups,
rather than to secondary treatment of retinopathy.
Arterial stiffness is an important predictor of cardiovascular
events, and non-invasively calculated values showed a powerful
correlation with invasive measurements.
32
In a recent study, the
relationship with anti-angiogenic drugs and increased aortic
stiffness was demonstrated in an adult population with cancer,
independent of blood pressure changes.
12
We found that the aortic
elastic indices in the treatment group were significantly different
from the control group. Moreo
et al
. showed that an increase in
arterial stiffness appeared after only two weeks and decreased
in the patients whose treatment was ended.
10
On the other
hand, there was no significant difference in aortic elastic indices
between the LPC and IVA groups; however, higher vascular
stiffness values would make it possible to determine whether an
increase in this parameter was the direct result of aflibercept or
due to hypertension and only indirectly caused by the drug.
Currently, little is known about the systemic effects of
intra-ocular anti-VEGF injections. We have limited knowledge
and experience, especially in intravitreal aflibercept in ROP
treatment, and there are only a few reports with small series in
the literature. In the present study, we evaluated both the cardiac
effects of aflibercept and laser photocoagulation treatment in
infants diagnosed with ROP in comparison to the untreated
infant group. Using echocardiography, we demonstrated some
differences that point to subtle diastolic dysfunction but we
could not show any differences in aortic elastic parameters
between IVA and LPC treatment compared with controls.
Limitations
The small sample size of each group and the retrospective, single-
centre,cross-sectionaldesignconstitutethemainlimitationsof our
study. Another limitation is that the patients’ echocardiographic
assessment should have been done before the treatment because
it is important to obtain baseline strain measurements to observe
subsequent changes after anti-VEGF treatment. Because the link
between the agent and the cardiovascular outcomes could not
be confirmed clearly, more observational studies are needed to
confirm cardiovascular safety during long-term therapy.
Conclusion
This study assessing ventricular function using TDI demonstrated
diminutive diastolic changes in the cardiac parameters measured
by echocardiography. The ultimate future goal would be to
identify these asymptomatic infants accurately with speckle-
tracking echocardiography, using a more sensitive imaging
method. Adequately powered, well-designed clinical trials are
necessary to clearly define the cardiovascular effects of these
anti-VEGF agents in infants.
References
1.
Chang HH, Larson J, Blencowe H,
et al
. Preventing preterm births: anal-
ysis of trends and potential reductions with interventions in 39 countries
with very high human development index.
Lancet
2013:
381
: 223–234.
2.
Gilbert C. Retinopathy of prematurity: a global perspective of the
epidemics, population of babies at risk and implications for control.
Early Hum Dev
2008:
84
: 77–82.
3.
Early Treatment for Retinopathy of Prematurity Cooperative Group.
Revised indications for the treatment of retinopathy of prematurity:
results of the early treatment for retinopathy of prematurity randomized
trial.
Arch Ophthalmol
2003:
121
: 1684–1694.
4.
Lutty GA, McLeod DS, Bhutto I,
et al
. Effect of VEGF trap on normal
retinal vascular development and oxygen-induced retinopathy in the
dog.
Invest Ophthalmol Visual Sci
2011:
52
: 4039–4047.
5.
Salman AG, Said AM. Structural, visual and refractive outcomes of
intravitreal aflibercept injection in high-risk prethreshold type 1 retin-
opathy of prematurity.
Ophthalmic Res
2015:
53
: 15–20.
6.
Mintz-Hittner HA, Kennedy KA, Chuang AZ,
et al
. Efficacy of intra-
vitreal bevacizumab for stage 3+ retinopathy of prematurity.
N Engl J
Med
2011:
364
: 603–615.
7.
Sukgen EA, Soker G, Kocluk Y,
et al
. Effect of intravitreal aflibercept
on central retinal arterial blood flow in type 1 retinopathy of prematu-
rity.
Eur J Ophthalmol
2017:
27
(6): 751–755.
8.
Sato T, Wada K, Arahori H,
et al
. Serum concentrations of bevaci-
zumab (avastin) and vascular endothelial growth factor in infants with
retinopathy of prematurity.
Am J Ophthalmol
2012:
153
: 327–333.
9.
Wu WC, Shih CP, Lien R,
et al
. Serum vascular endothelial growth
factor after bevacizumab or ranibizumab treatment for retinopathy of
prematurity.
Retina
2017
37
(4): 694–701.
10. Moreo A, Vallerio P, Ricotta R,
et al
. Effects of cancer therapy targeting
vascular endothelial growth factor receptor on central blood pressure
and cardiovascular system.
Am J Hypertens
2016:
29
: 158–162.
11. Wasserstrum Y, Kornowski R, Raanani P,
et al
. Hypertension in cancer
patients treated with anti-angiogenic based regimens.
Cardio-Oncology
2015:
1
: 6.
12. Alivon M, Giroux J, Briet M,
et al
. Large artery stiffness and hyper-
tension after antiangiogenic drugs: influence on cancer progression.
J
Hypertens
2015:
33
: 1310–1317.
13. Elsaughier SM, Ghaleb R, Mansour H. Effect of time delay of PDA
closure on the aortic stiffness index and its relationship with cardiac
function.
Cardiovasc J Afr
2019:
30
: 1–6.
14. Quinones MA, Otto CM, Stoddard M,
et al
. Recommendations
for quantification of Doppler echocardiography: a report from the
Doppler Quantification Task Force of the Nomenclature and Standards
Committee of the American Society of Echocardiography. J
Am Soc
Echocard
2002:
15
: 167–184.
15. Fahey M, Ko HH, Srivastava S,
et al
. A comparison of echocardio-
graphic techniques in determination of arterial elasticity in the pediatric
population.
Echocardiography
2009:
26
: 567–573.
16. CATT Research Group, Martin DF, Maguire MG,
et al
. Ranibizumab
and bevacizumab for neovascular age-related macular degeneration.
N
Engl J Med
2011:
364
: 1897–1908.
17. Simons M, Eichmann A. “On-target” cardiac effects of anticancer
drugs: lessons from new biology.
J Am Coll Cardiol
2012:
60
: 626–627.
18. Scott LJ, Chakravarthy U, Reeves BC, et al. Systemic safety of anti-
VEGF drugs: a commentary.
Expert Opin Drug Saf
2015:
14
: 379–388.
19. Daher IN, Yeh ET. Vascular complications of selected cancer therapies.
Nat Clin Pract Cardiovasc Med
2008:
5
: 797–805.
20. Carmeliet P, Ferreira V, Breier G, et al. Abnormal blood vessel devel-
opment and lethality in embryos lacking a single VEGF allele.
Nature