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Impact of left atrial and diastolic ventricular dysfunction on mortality in patients with aortic stenosis

Institution:	1. Cardiology Department, Heart Valve Centre, Lille Catholic Hospitals, ETHICS EA 7446, Lille Catholic University, 59462 Lomme Cedex, France;2. Centre Hospitalier Universitaire d’Amiens, 80054 Amiens, France;3. EA 7517 MP3CV, Jules Verne University of Picardie, 80054 Amiens, France;1. Cardiology Department, Vall d’Hebron University Hospital, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, Pg. Vall d’Hebron 119–129, 08035 Barcelona, Spain;2. Nuclear Cardiology Department, Vall d’Hebron University Hospital, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain;3. Centro de Investigación Biomédica En Red: Enfermedades Cardiovasculares (CIBER-CV), 28029 Madrid, Spain;4. Centro de Investigación Biomédica En Red: Epidemiología y Salud Pública (CIBER-ESP), 28029 Madrid, Spain;1. Emergency Department, Toulouse University Hospital, 31059 Toulouse, France;2. Intensive Cardiac Care Unit, Cardiology Department, Toulouse University Hospital, 31059 Toulouse, France;3. CERPOP, Toulouse University, Inserm, UPS, Toulouse, France;1. Service de médecine intensive réanimation, département médico-universitaire APPROCHES, hôpital Tenon, AP–HP, Sorbonne université, 75020 Paris, France;2. Groupe de recherche clinique CARMAS, université Paris-Est Créteil, 94010 Créteil, France;3. Department of Cardiology, UNICO Cardio-Oncology Program, hôpital Saint-Antoine, AP–HP, 75012 Paris, France;4. Inserm U 856, 75013 Paris, France;5. Division of Intensive Care, Department of Acute Medicine, University Hospitals of Geneva, 1205 Geneva, Switzerland;6. Laboratory of Nephrology, Department of Medicine, University Hospitals of Geneva, 1205 Geneva; and Department of Cell Physiology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland;7. Service de médecine intensive réanimation, hôpital Saint-Antoine, AP–HP, Sorbonne université, 75012 Paris, France;8. Service de médecine intensive réanimation, département médico-universitaire médecine, hôpitaux universitaires Henri Mondor-Albert Chenevier, AP–HP, 94000 Créteil, France;9. Service de médecine intensive réanimation, centre hospitalier melun, groupe hospitalier Sud Ile-de-France, 77000 Melun, France;10. Réanimation médicale et toxicologique, hôpital Lariboisière, AP–HP, université de Paris, Inserm UMRS-1144, 75010 Paris, France;11. UMR-S ICAN 1166, Sorbonne université, 75013 Paris, France;1. Paediatric and Adult Congenital Cardiology Unit, CHU Toulouse, 330, avenue de Grande Bretagne, 31059 Toulouse cedex 9, France;2. Institut des maladies métaboliques et cardiovasculaires, université de Toulouse, Inserm U1048, I2MC, 31432 Toulouse, France;3. Department of Cardiology, Saint-Antoine and Tenon Hospital, AP–HP, Inserm UMRS-ICAN 1166 and Sorbonne université, 75013 Paris, France;4. Centre de recherche cardiovasculaire de Paris, Inserm U970, 75015 Paris, France;5. Institut des cardiopathies congénitales de Tours, CHRU de Tours, centre hospitalier regional universitaire de Tours, université François-Rabelais, 37000 Tours, France;6. Department of Paediatric and Adult Congenital Cardiology, University Hospital of Bordeaux; IHU Liryc, fondation Bordeaux université, centre de recherche cardiothoracique de Bordeaux, Inserm, 33600 Pessac, France;7. Service de cardiologie pédiatrique, groupe hospitalier Est, CHU de Lyon, 69677 Bron, France;8. Centre de référence des malformations cardiaques congénitales complexes, M3C, Adult Congenital Heart Disease Unit, hôpital européen Georges-Pompidou, AP–HP, Paris Cité University, 75015 Paris, France;1. Department of Cardiology, hôpital Cochin, hôpitaux universitaire Paris centre, AP–HP, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France;2. Université Paris Cité, 75006 Paris, France;3. Medical Intensive Care Unit, hôpital Cochin, hôpitaux universitaire Paris centre, AP–HP, 75014 Paris, France;4. Inserm U970, Paris Cardiovascular Research Center (PARCC), Georges-Pompidou European Hospital, 75015 Paris, France;1. Département de cardiologie, CHU Timone, 13005 Marseille, France;2. C2VN, Aix-Marseille université, Inserm, INRA, 13005 Marseille, France;3. Faculté de médecine, Aix-Marseille université, 13385 Marseille, France;4. Service de cardiologie, centre hospitalier universitaire trousseau et Faculté de médecine, université de Tours, 37032 Tours, France;5. EA4245 Transplantation immunité inflammation, université de Tours, 37032 Tours, France;6. Département de cardiologie, CHU Nord, 13015 Marseille, France;7. Service d’information médicale, d’épidémiologie et d’économie de la santé, centre hospitalier universitaire et Faculté de médecine, EA7505, université de Tours, 37044 Tours, France

Abstract:	BackgroundDiastolic dysfunction (DD) is common in severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF ≥ 50%).AimTo determine the impact of American Society of Echocardiography/European Association of Cardiovascular Imaging-recommended DD grading and left atrial strain on mortality in a cohort of patients with severe AS and preserved LVEF.MethodsWe studied patients with severe AS (aortic valve area indexed < 0.6 cm²/m² and/or aortic valve area < 1 cm²), LVEF ≥ 50% and no or mild AS-related symptoms. The endpoint was all-cause mortality.ResultsA total of 387 patients (median age 76 years; 53% women) were studied. During a median follow-up of 57 (interquartile range 37; 83) months, 158 patients died. After adjustment for prognostic factors, patients with grade II or III DD had an increased mortality risk versus patients with grade I DD (adjusted hazard ratio (aHR) 1.62, 95% confidence interval (CI) 1.11–2.38; P = 0.013; aHR 4.73, 95% CI 2.49–8.99; P < 0.001; respectively). Adding peak atrial longitudinal strain (PALS) ≤ 14% to a multivariable model including DD grade improved predictive performance, with better global model fit, reclassification and discrimination. Patients with grade III DD or grade II DD + PALS ≤ 14% displayed an increased mortality risk versus patients with grade I DD + PALS > 14% (aHR 4.17, 95% CI 2.46–7.06; P < 0.0001). Those with grade I DD + PALS ≤ 14% or grade II DD + PALS > 14% were at intermediate risk (aHR 1.63, 95% CI 1.07–2.49; P = 0.024).ConclusionsOur results demonstrate the strong relationship between DD and mortality in patients with severe AS and preserved LVEF. Patients with grade III or grade II DD and impaired PALS are at very high risk. These data demonstrate the importance of a comprehensive assessment of diastolic function in patients with severe AS.

Keywords:	Aortic stenosis Diastolic dysfunction Left atrial strain Outcome aHR"} {"#name":"keyword" "$":{"id":"kw0030"} "$$":[{"#name":"text" "_":"adjusted hazard ratio AS"} {"#name":"keyword" "$":{"id":"kw0040"} "$$":[{"#name":"text" "_":"aortic stenosis ASE"} {"#name":"keyword" "$":{"id":"kw0050"} "$$":[{"#name":"text" "_":"American Society of Echocardiography AVA"} {"#name":"keyword" "$":{"id":"kw0060"} "$$":[{"#name":"text" "_":"aortic valve area AVR"} {"#name":"keyword" "$":{"id":"kw0070"} "$$":[{"#name":"text" "_":"aortic valve replacement CI"} {"#name":"keyword" "$":{"id":"kw0080"} "$$":[{"#name":"text" "_":"confidence interval DD"} {"#name":"keyword" "$":{"id":"kw0090"} "$$":[{"#name":"text" "_":"diastolic dysfunction EACVI"} {"#name":"keyword" "$":{"id":"kw0100"} "$$":[{"#name":"text" "_":"European Association of Cardiovascular Imaging IDI"} {"#name":"keyword" "$":{"id":"kw0110"} "$$":[{"#name":"text" "_":"integrated discrimination improvement IQR"} {"#name":"keyword" "$":{"id":"kw0120"} "$$":[{"#name":"text" "_":"interquartile range LA"} {"#name":"keyword" "$":{"id":"kw0130"} "$$":[{"#name":"text" "_":"left atrial LACS"} {"#name":"keyword" "$":{"id":"kw0140"} "$$":[{"#name":"text" "_":"left atrial strain during the conduit phase LAS"} {"#name":"keyword" "$":{"id":"kw0150"} "$$":[{"#name":"text" "_":"left atrial strain LV"} {"#name":"keyword" "$":{"id":"kw0160"} "$$":[{"#name":"text" "_":"left ventricular LVEF"} {"#name":"keyword" "$":{"id":"kw0170"} "$$":[{"#name":"text" "_":"left ventricular ejection fraction NRI"} {"#name":"keyword" "$":{"id":"kw0180"} "$$":[{"#name":"text" "_":"net reclassification improvement PACS"} {"#name":"keyword" "$":{"id":"kw0190"} "$$":[{"#name":"text" "_":"peak atrial contraction strain PALS"} {"#name":"keyword" "$":{"id":"kw0200"} "$$":[{"#name":"text" "_":"peak atrial longitudinal strain
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