Multiparametric Strategy to Predict Early Disease Decompensation in Asymptomatic Severe Aortic Regurgitation

Abstract

Background: Use of the current echocardiography-based indications for aortic regurgitation (AR) surgery might result in late valve replacement at the stage of irreversible myocardial damage. Therefore, we aimed to identify simple models combining multiple echocardiography or magnetic resonance imaging (MRI)–derived indices and natriuretic peptides (BNP [brain natriuretic peptide] or NT-proBNP [N-terminnal pro-B type natriuretic peptide]) to predict early disease decompensation in asymptomatic severe AR. Methods: This prospective and multicenter study included asymptomatic patients with severe AR, preserved left ventricular ejection fraction (>50%), and sinus rhythm. The echocardiography and MRI images were analyzed centrally in the CoreLab. The study end point was the onset of indication for aortic valve surgery as per current guidelines. Results: The derivative cohort consisted of 127 asymptomatic patients (age 45±14 years, 84% males) with 41 (32%) end points during a median follow-up of 1375 (interquartile range, 1041–1783) days. In multivariable Cox regression analysis, age, BNP, 3-dimensional vena contracta area, MRI left ventricular end-diastolic volume index, regurgitant volume, and a fraction were identified as independent predictors of end point (all P <0.05). However, a combined model including one parameter of AR assessment (MRI regurgitant volume or regurgitant fraction or 3-dimensional vena contracta area), 1 parameter of left ventricular remodeling (MRI left ventricular end-diastolic volume index or echocardiography 2-dimensional global longitudinal strain or E wave), and BNP showed significantly higher predictive accuracy (area under the curve, 0.74–0.81) than any parameter alone (area under the curve, 0.61–0.72). These findings were confirmed in the validation cohort (n=100 patients, 38 end points). Conclusions: In asymptomatic severe AR, multimodality and multiparametric model combining 2 imaging indices with natriuretic peptides, showed high accuracy to identify early disease decompensation. Further prospective studies are warranted to explore the clinical benefit of implementing these models to guide patient management. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02910349

Optimizing the Timing of Aortic Valve Surgery: A Multiparametric Approach

“…Indeed, several large studies have shown that asymptomatic patients with severe AR and a normal left ventricular ejection fraction have better pre and postoperative outcomes if surgical intervention takes place below the currently recommended thresholds, avoiding potential accrual or residual risk or limitation that persists after procedure. 17,18 The present study by Kockova et al, 16 together with others, proposes an alternative approach to surgical intervention, with the aim of surgery taking place before irreversible myocardial damage has occurred. Future studies will be needed to comprehensively redefine the core processes involved (hemodynamic changes, structural and functional changes, and myocardial consequences) and use these to reclassify disease stages.…”

“…13,14 Importantly, elevated natriuretic peptides, impaired global longitudinal strain, and myocardial fibrosis, detected on late gadolinium enhancement imaging, are all associated with early adverse outcomes and an increased risk of mortality following aortic valve surgery. 9,10,15 In the current issue of Circulation: Cardiovascular Imaging, Kockova et al 16 present data on a multiparametric scoring system that combined echocardiographic or CMR-derived parameters and serum natriuretic peptides to detect early disease decompensation in patients with asymptomatic severe AR and preserved left ventricular systolic function. This prospective multicenter study recruited 127 patients (age 45±14 years, 84% males) with asymptomatic severe AR and preserved left ventricular systolic function, all of whom underwent a comprehensive baseline assessment comprising serum natriuretic peptides, transthoracic echocardiography, and CMR.…”

“…Furthermore, the performance of this proposed model remained robust in an external validation cohort. In the study by Kockova et al, 16 indices of AR severity outperformed indices of left ventricular remodeling in predicting early disease progression; and CMR-derived measures of AR severity outperformed all clinically relevant echocardiographic measures of AR severity. Additionally, this study demonstrated that the single most powerful predictors of disease progression were all indices of AR severity, rather than indices of left ventricular remodeling.…”

Rationale and design of the ELEANOR trial early aortic valve surgery versus watchful waiting strategy in severe asymptomatic aortic regurgitation, ACRONYM: ELEANOR

“…The selection of CMR-derived RF and RV cut-off values are based on previously published prognostic data of four independent groups: Myerson et al (RV >42 mL, RF >33 %) [ 14 ], Harris et al (RV >50 mL, RF ≥37 %) [ 15 ], Vejpongsa et al (RF >35 %) [ 16 ] and our data, Kockova et al (RV >45 mL and RF >34 %) [ 17 ]. Left ventricular diameters and volumes have lower predictive accuracy, however, a combination of AR quantification parameters (cut-offs: RV > 45 mL and RF >34 %) and LV EDVI (cut-off LV EDVI >125 mL/m2) showed high accuracy in identifying patients at risk of early clinical deterioration requiring surgery during a median of 399 (IQR 209) days [ 17 ].

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“…Recently introduced multimodality-imaging markers of AR quantification or LV remodeling assessed by using 3-dimensional echocardiography (ECHO) or cardiac magnetic resonance (CMR) along serum natriuretic peptide level [ 11 , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] ], have shown high accuracy in identifying asymptomatic patients who are at risk of early clinical progression and could potentially benefit from early surgical intervention [ 14 , 17 ]. Specifically, the approach integrating CMR-derived AR quantification with LV remodeling assessment has shown very promising results in observational studies [ 14 , 17 ].…”