Drug-induced aortic valve stenosis: An under recognized entity

Pierre-Vladimir Ennezat (1) , Patrick Bruneval (2) , Daniel Czitrom (3) , Jean-Pierre Gueffet (4) , Nicolas Piriou (5) , Jean Noel Trochu , Odile Patra , Benedicte Blanchard-Lemoine , Xavier Halna Du Fretay , Pierre Nazeyrollas (6) , Bernard Assoun , Yannick Jobic (7) , Eric Brochet (8) , Emmanuel Bogino , Raymond Roudaut (9) , Caroline Augier (10) , Lorraine Greffe , Helene Petit-Eisenmann (11, 12, 13) , Camille Dambrin (14) , Olivier Chavanon (15) , Louis Guillou (16) , Dominique Grisoli (17) , Pierre Morera , Carlo Banfi (18) , Jean Paul Remadi , Olivier Fabre , Andre Vincentelli (18) , Sylvie Lantuejoul (19) , Jean-Fortune Ikoli , Marie-Christine Copin (18) , Marie-Christine Malergue (20, 21, 22) , Sylvestre Marechaux (23, 24) , Christophe Tribouilloy (24)

1 Département de cardiologie et hypertension
2 Immunopathologie humaine
3 IMM - Institut Mutualiste de Montsouris
4 Institut du thorax
5 ITX-lab - Unité de recherche de l'institut du thorax
6 CHU Reims - Centre Hospitalier Universitaire de Reims
7 Département Cardiologie
8 LVTS (UMR_S_1148 / U1148) - Laboratoire de Recherche Vasculaire Translationnelle
9 Département de cardiologie
10 UGA UFRM - Université Grenoble Alpes - UFR Médecine
11 Nouvel Hôpital Civil de Strasbourg
12 CHU Strasbourg
13 UNISTRA - Université de Strasbourg
14 Chirurgie Cardio-Vasculaire
15 LLSETI - Langages, Littératures, Sociétés, Études Transfrontalières et Internationales
16 Oncology - Pathology - Anatomy
17 MEPHI - Microbes évolution phylogénie et infections
18 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]
19 Département d'anatomie et cythologie pathologique
20 Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes]
21 CIC-IT Rennes
22 LTSI - Laboratoire Traitement du Signal et de l'Image
23 Groupement Hospitalier de l'Institut Catholique de Lille
24 MP3CV - Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517

Background: We have been intrigued by the observation that aortic stenosis (AS) may be associated with characteristic features of mitral drug-induced valvular heart disease (DI-VHD) in patients exposed to valvulopathic drugs, thus suggesting that beyond restrictive heart valve regurgitation, valvulopathic drugs may be involved in the pathogenesis of AS. Methods: Herein are reported echocardiographic features, and pathological findings encountered in a series of patients suffering from both AS (mean gradient > 15 mm Hg) and mitral DI-VHD after valvulopathic drugs exposure. History of rheumatic fever, chest radiation therapy, systemic disease or bicuspid aortic valve disease were exclusion criteria. Results: Twenty-five (19 females, mean age 62 years) patients having both AS and typical features of mitral DI-VHD were identified. Mean transaortic pressure gradient was 32+/-13 mm Hg. Aortic regurgitation was >= mild in 24 (96%) but trivial in one. Known history of aortic valve regurgitation following drug initiation prior the development of AS was previously diagnosed in 17 patients (68%). Six patients underwent aortic valve replacement and 3 both aortic and mitral valve replacement. In the 9 patients with pathology analysis, aortic valvular endocardium was markedly thickened by dense non-inflammatory fibrosis, a characteristic feature of DI-VHD. Conclusion: The association between AS and typical mitral DI-VHD after valvulopathic drug exposure may not be fortuitous. Aortic regurgitation was usually associated to AS and preceded AS in most cases but may be lacking. Pathology demonstrated the potential role of valvulopathic drugs in the development of AS. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Domaines: Sciences du Vivant [q-bio]

Pierre-Vladimir Ennezat, Patrick Bruneval, Daniel Czitrom, Jean-Pierre Gueffet, Nicolas Piriou, et al.. Drug-induced aortic valve stenosis: An under recognized entity. International Journal of Cardiology, 2016, 220, pp.429-434. ⟨10.1016/j.ijcard.2016.06.112⟩. ⟨hal-03580779⟩