Author + information
- Received September 6, 2011
- Revision received December 5, 2011
- Accepted December 18, 2011
- Published online July 31, 2012.
- Denise van der Linde, MSc⁎,
- Ingrid M.B.H. van de Laar, MD†,
- Aida M. Bertoli-Avella, MD, PhD†,
- Rogier A. Oldenburg, MD, PhD†,
- Jos A. Bekkers, MD‡,
- Francesco U.S. Mattace-Raso, MD, PhD§,
- Anton H. van den Meiracker, MD, PhD§,
- Adriaan Moelker, MD, PhD∥,
- Fop van Kooten, MD, PhD¶,
- Ingrid M.E. Frohn-Mulder, MD#,
- Janneke Timmermans, MD⁎⁎,
- Els Moltzer, PhD§,
- Jan M. Cobben, MD, PhD††,
- Lut van Laer, PhD‡‡,
- Bart Loeys, MD, PhD‡‡,
- Julie De Backer, MD, PhD§§,
- Paul J. Coucke, PhD§§,
- Anne De Paepe, MD, PhD§§,
- Yvonne Hilhorst-Hofstee, MD∥∥,
- Marja W. Wessels, MD, PhD† and
- Jolien W. Roos-Hesselink, MD, PhD⁎,⁎ ()
- ↵⁎Reprints requests and correspondence:
Dr. Jolien W. Roos-Hesselink, Department of Cardiology, Ba-583a, Erasmus Medical Center, P. O. Box 2040, 3000 CA, Rotterdam, the Netherlands
Objectives The purpose of this study was describe the cardiovascular phenotype of the aneurysms-osteoarthritis syndrome (AOS) and to provide clinical recommendations.
Background AOS, caused by pathogenic SMAD3 variants, is a recently described autosomal dominant syndrome characterized by aneurysms and arterial tortuosity in combination with osteoarthritis.
Methods AOS patients in participating centers underwent extensive cardiovascular evaluation, including imaging, arterial stiffness measurements, and biochemical studies.
Results We included 44 AOS patients from 7 families with pathogenic SMAD3 variants (mean age: 42 ± 17 years). In 71%, an aortic root aneurysm was found. In 33%, aneurysms in other arteries in the thorax and abdomen were diagnosed, and in 48%, arterial tortuosity was diagnosed. In 16 patients, cerebrovascular imaging was performed, and cerebrovascular abnormalities were detected in 56% of them. Fifteen deaths occurred at a mean age of 54 ± 15 years. The main cause of death was aortic dissection (9 of 15; 60%), which occurred at mildly increased aortic diameters (range: 40 to 63 mm). Furthermore, cardiac abnormalities were diagnosed, such as congenital heart defects (6%), mitral valve abnormalities (51%), left ventricular hypertrophy (19%), and atrial fibrillation (22%). N-terminal brain natriuretic peptide (NT-proBNP) was significantly higher in AOS patients compared with matched controls (p < 0.001). Aortic pulse wave velocity was high-normal (9.2 ± 2.2 m/s), indicating increased aortic stiffness, which strongly correlated with NT-proBNP (r = 0.731, p = 0.005).
Conclusions AOS predisposes patients to aggressive and widespread cardiovascular disease and is associated with high mortality. Dissections can occur at relatively mildly increased aortic diameters; therefore, early elective repair of the ascending aorta should be considered. Moreover, cerebrovascular abnormalities were encountered in most patients.
This work was funded partially by an Erasmus Fellowship to Dr. Bertoli-Avella; a Research Foundation Flanders grant to Dr. Loeys; the Flanders Fund for Scientific Research to Dr. De Backer as a Senior Clinical Researcher; and Methusalem grant number BOF08/01M01108 from Ghent University to Dr. De Paepe. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The first two authors contributed equally to this work.
- Received September 6, 2011.
- Revision received December 5, 2011.
- Accepted December 18, 2011.
- American College of Cardiology Foundation