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. 2024 Sep 6;3(10):101228.
doi: 10.1016/j.jacadv.2024.101228. eCollection 2024 Oct.

Mortality Burden for Patients With Untreated Aortic Regurgitation

Philippe Généreux  1 , Nicholas S Amoroso  2 , Vinod H Thourani  3 , Evelio Rodriguez  4 , Rahul P Sharma  5 , Duane S Pinto  6   7 , Michelle Kwon  8 , Michael Dobbles  8 , Patricia A Pellikka  9 , Linda D Gillam  1
Affiliations

Mortality Burden for Patients With Untreated Aortic Regurgitation

Philippe Généreux et al. JACC Adv. .

Abstract

Background: Aortic valve replacement (AVR) is indicated in patients with severe aortic regurgitation (AR); however, certain clinical factors may identify patients with less-than-severe AR at high mortality risk if untreated.

Objectives: The authors sought to characterize key associations with mortality across the spectrum of AR in patients not treated with AVR from a large, contemporary database.

Methods: We analyzed patients >18 years of age with documented AR assessment in a deidentified real-world data set from 27 U.S. institutions with appropriate permissions (egnite Database, egnite, Inc). Diagnosed AR severity was extracted from echocardiographic reports using a natural language processing-based algorithm. Cox multivariable analysis modeled the impact of key factors on untreated mortality according to AR severity.

Results: In total, 81,378 patients were included for analysis. Hazard ratios for mortality were 1.26 (95% CI: 1.18-1.35) and 2.37 (95% CI: 1.96-2.87) for moderate and severe AR, respectively. Other significant associations included left ventricular (LV) ejection fraction ≤55% (1.09 [95% CI: 1.02-1.15]), LV dilation (1.34 [95% CI: 1.21-1.48]), left atrial dilation (1.09 [95% CI: 1.03-1.16]), atrial fibrillation (1.11 [1.04-1.17]), and elevated B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide (1.71 [95% CI: 1.60-1.84]). Modeled mortality risk increased with the presence of these key factors both alone and in combination.

Conclusions: In patients with untreated AR, LV remodeling, left atrial remodeling, and other markers of cardiac damage are associated with substantial mortality risk, both for severe and moderate AR. Further study is needed to determine whether AVR is warranted in patients with less-than-severe AR with at-risk factors.

Keywords: aortic insufficiency; aortic regurgitation; aortic valve; aortic valve replacement; database; natural language processing.

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Conflict of interest statement

Funding for this work was provided by 10.13039/100019998JenaValve Technology, Inc. Analytical and editorial support was provided by egnite, Inc. Dr Généreux has served as a consultant for 4C Medical, Abbott Vascular, Abiomed, BioTrace Medical, Boston Scientific, Caranx Medical, Cardiovascular Systems Inc, Edwards Lifesciences, GE Healthcare, iRhythm Technologies, Medtronic, Opsens, Pi-Cardia, Puzzle Medical, Saranas, Shockwave, Soundbite Medical Inc, egnite, Inc, and Teleflex; is an advisor to Abbott Vascular, Abiomed, BioTrace Medical, Edwards Lifesciences, egnite, Inc, and Medtronic; has received speaker fees from Abbott Vascular, Abiomed, BioTrace Medical, Medtronic, Shockwave, and Siemens; is a principal investigator of 4C Medical for the AltaValve feasibility study, Cardiovascular Systems Inc for the Eclipse Trial, and Edwards Lifesciences for the EARLY-TAVR and PROGRESS trials; holds equity in Pi-Cardia, Puzzle Medical, Saranas, and Soundbite Medical Inc; and is a proctor for and has received institutional grants from 10.13039/100006520Edwards Lifesciences. Dr Amoroso has served as a consultant and proctor for JenaValve Technology, Inc and Abbott; has received speaker fees from Boston Scientific; has served as a consultant to Edwards Lifesciences and Siemens; is on the advisory board and has an equity interest in Nininger Medical. Dr Thourani is on the advisory board or in research for Edwards Lifesciences, Artivion, Abbott Vascular, AtriCure, JenaValve Technology, Inc, Shockwave, Boston Scientific, Medtronic, and Dasi Simulations; is on the advisory board and is a consultant for egnite, Inc. Dr Rodriguez has received consulting fees, speaker fees, and honoraria from Edwards Lifesciences; consulting fees from egnite, Inc; consulting fees, speaker fees, clinical educator fees, and honoraria from AtriCure; consulting fees, speaker fees, honoraria, and a research grant from Abbott; speaker fees from Phillips; and consulting fees from CardioMech and Teleflex. Dr Sharma has received consulting fees, speaker fees, and honoraria from Edwards Lifesciences, has received consulting fees and has equity interest in egnite, Inc; and has received speaker fees and honoraria from Boston Scientific and Abbott. Dr Pinto has served as a consultant for Abbott Vascular, Abiomed, Boston Scientific, Inari, Philips, Terumo, Teleflex, Biotronik, Medtronic, NuPulseCV, and Magenta; is an employee of and has an equity interest in JenaValve Technology, Inc. Dr Kwon has an equity interest in and is an employee of egnite, Inc. Dr Dobbles has an equity interest in and is an employee of egnite, Inc. Dr Pellikka has received research support from Ultromics and 10.13039/100006520Edwards Lifesciences. Dr Gillam has served as a consultant for Edwards Lifesciences, Medtronic, and Philips; is on the advisory board for egnite, Inc; and has core lab contracts with Abbott, Edwards Lifesciences, and Medtronic for which she receives no direct compensation.

Figures

None
Graphical abstract
Figure 1
Figure 1
Proportion of Patients Exhibiting Individual Key Factors∗ at Time of Worst AR Diagnosis Within Study Window ∗Key factors defined as follows: LV dilation, as LVESDi >25 mm/m2 and/or LVESVi ≥45 mL/m2; LA dilation, as LAVi >34 mL/m2; AF, per International Classification of Diseases-10th revision codes; elevated BNP/NT-proBNP, as BNP ≥400 pg/mL and/or NT-proBNP ≥1,500 pg/mL. AF = atrial fibrillation; AR = aortic regurgitation; BNP = B-type natriuretic peptide; LA = left atrial; LAVi = left atrial volume index; LV = left ventricular; LVEF = left ventricular ejection fraction; LVESDi = left ventricular end-systolic dimension index; LVESVi = left ventricular end-systolic volume index; NT-proBNP = N-terminal pro-B-type natriuretic peptide.
Figure 2
Figure 2
Modeled Mortality Risk Contributions of Key Factors∗ and AR Severity ∗Key factors defined as follows: LV dilation, as LVESDi >25 mm/m2 and/or LVESVi ≥45 mL/m2; LA dilation, as LAVi >34 mL/m2; AF, per International Classification of Diseases-10th revision codes; BNP/NT-proBNP, as elevated BNP ≥400 pg/mL and/or NT-proBNP ≥1,500 pg/mL. Abbreviations as in Figure 1.
Central Illustration
Central Illustration
Mortality Burden for Patients With Untreated Aortic Regurgitation Impact of untreated aortic regurgitation according to severity and factors associated with 2-year mortality. (Top left) Kaplan-Meier summary analysis of observed mortality with untreated aortic regurgitation over up to 2 years of follow-up after the index documented diagnosis for cohorts of interest, with censoring at last documented clinical encounter or treatment with aortic valve replacement. Analysis of all possible documented severities is also available as Supplemental Material. Because of the time-varying nature of the data set for this study, in this analysis, Aortic regurgitation severity is treated as a time-varying covariate. (Bottom left) Modeled hazards for key factors of interest in this study. (Right) 2-year modeled mortality according to different AR severities and key factors of interest. key factors defined as follows: LV dilation, as LVESDi >25 mm/m2 and/or LVESVi ≥45 mL/m2; LA dilation, as LAVi >34 mL/m2; AF, per International Classification of Diseases-10th revision codes; BNP/NT-proBNP, as elevated BNP ≥400 pg/mL and/or NT-proBNP ≥1,500 pg/mL. Abbreviations as in Figure 1.
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References

    1. d'Arcy J.L., Coffey S., Loudon M.A., et al. Large-scale community echocardiographic screening reveals a major burden of undiagnosed valvular heart disease in older people: the OxVALVE Population Cohort Study. Eur Heart J. 2016;37:3515–3522. - PMC - PubMed
    1. Gossl M., Stanberry L., Benson G., et al. Burden of undiagnosed valvular heart disease in the elderly in the community: heart of new ulm valve study. JACC Cardiovasc Imaging. 2023;16:1118–1120. - PubMed
    1. Dujardin K.S., Enriquez-Sarano M., Schaff H.V., Bailey K.R., Seward J.B., Tajik A.J. Mortality and morbidity of aortic regurgitation in clinical practice. A long-term follow-up study. Circulation. 1999;99:1851–1857. - PubMed
    1. Gaasch W.H., Carroll J.D., Levine H.J., Criscitiello M.G. Chronic aortic regurgitation: prognostic value of left ventricular end-systolic dimension and end-diastolic radius/thickness ratio. J Am Coll Cardiol. 1983;1:775–782. - PubMed
    1. Carabello B.A., Williams H., Gash A.K., et al. Hemodynamic predictors of outcome in patients undergoing valve replacement. Circulation. 1986;74:1309–1316. - PubMed

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