Adult Congenital Heart Disease
Daan Bosshardt, MD
PhD student
Amsterdam Medical Center
Amsterdam, Noord-Holland, Netherlands
Daan Bosshardt, MD
PhD student
Amsterdam Medical Center
Amsterdam, Noord-Holland, Netherlands
Mitzi M. van Andel, MD
PhD student
Amsterdam Medical Center, Netherlands
Vivian de Waard, PhD
Associate Professor medical biochemistry
Amsterdam Medical Center, Netherlands
Eric M. Schrauben, PhD
Scientific researcher applied MR physics
Amsterdam Medical Center
Toronto, Ontario, Netherlands
Roland R. van Kimmenade, MD, PhD
Cardiologist
Radboud University Medical Center, Netherlands
Arthur J.H.A. Scholte, MD, PhD
Cardiologist
Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands
Michael G. Dickinson, MD, PhD
Cardiologist
University Medical Center Groningen, Netherlands
Aeilko H. Zwinderman, PhD
Professor of biostatistics
Amsterdam Medical Center, Netherlands
Barbara J. Mulder, MD, PhD
Cardiologist
Amsterdam Medical Center, Netherlands
Aart J. Nederveen, PhD
Professor applied MR physics
Amsterdam Medical Center, Netherlands
Pim van Ooij, PhD
Assistant professor cardiovascular MRI
Amsterdam Medical Center, Netherlands
Maarten Groenink, MD, PhD
Cardiologist
Amsterdam Medical Center, Netherlands
Mean aortic root dilatation rate in Marfan syndrome (MFS) is estimated to be 1.3-3.5mm/year (1). Resveratrol, a dietary supplement, has been shown to slow aortic dilatation rate in MFS mice. However, the effect of Resveratrol on aortic dilatation and aortic function in MFS patients has not been investigated yet.
Methods:
In this prospective observational multicenter trial, MFS patients with a native or surgically replaced aortic root received 500mg Resveratrol for a duration of one year. Primary endpoint was change of magnetic resonance imaging (MRI) derived aortic dimensions at predefined levels in the thoracic aorta. The aorta was visualized using an ECG gated Dixon 3D sequence with spatial resolution 0.73 x 0.73 x 1.25 mm. Wall shear stress (WSS) and velocity was measured with a 4D flow MRI sequence with parameters: spatial resolution: 2.5 x 2.5 x 2.5 mm3; temporal resolution: ~33 ms; echo time, repetition time / flip angle 2.1msec/3.9msec/8°; velocity encoding: 150–250 cm/s; acceleration with Prospective Undersampling in Multiple Dimensions (2). Cohort-averaged 3D velocity and WSS atlases from healthy subjects were used to quantify regions with abnormal WSS and velocity magnitude and direction (image 1) (3, 4).
Results:
Fifty-seven patients, mean age 36.5 ± 8.8 years, of which 28 males (49%) were included. In total, 26 (46%) had undergone aortic root replacement prior to the study. All aortic dimensions remained stable after 1.2 ± 0.28 years follow-up, particularly on the aortic root level of non-operated subjects (from 41.4 ± 4.4 mm to 41.2 ± 4.4 mm, p=0.517, growth rate -0.16 ± 1.29 mm/year) (table 1). Growth rate in the distal aorta and mean arterial pressure were positively correlated (Spearman r: 0.349, n=57, p=0.008).
No significant changes in mean WSS magnitude and flow velocities were observed (image 2) Abnormally directed WSS (mm2) in the outer aortic arch increased significantly from 0.0 (IQR: 0.0 - 4.1) to 2.0 (IQR: 0.0 – 30.0), p=0.002. Median amount of abnormally increased WSS (cm2) in the inner aortic arch aorta decreased from 18.3 (IQR: 8.1 – 69.5) to 0.0 (IQR: 0.0 – 34.9), p=0.008 for patients with abnormal WSS at baseline in the same region (n=14). We found a positive correlation between native aortic root growth and increase in WSS during the trial in the outer ascending aorta (Pearson r: 0.537, n=26, p=0.005).
Conclusion:
No significant changes in aortic dimensions after one year of Resveratrol use might be a first sign of stabilization of aortic dilatation. The decrease in some regional abnormal WSS patterns could possibly be attributed to Resveratrol. Furthermore, the correlation between various 4D flow parameters and aortic growth, highlight the potential of these parameters as biomarkers for MFS. Thus, our results warrant a subsequent larger, ideally randomized study with a longer follow-up period, to test this hypothesis.