Clinical Investigation
Aortic Stenosis
Prognostic Value of Left Atrial Strain in Aortic Stenosis: A Competing Risk Analysis

https://doi.org/10.1016/j.echo.2022.10.011Get rights and content

Highlights

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    LA strain is a key imaging biomarker for risk-stratifying AS with preserved LVEF.

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    LA strain outperformed AS hemodynamic indices and LV GLS in predicting outcomes.

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    This prognostic value was independent of clinical variables and NT-proBNP.

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    LASr < 20%, LAScd < 6%, and LASct < 12% enhanced discrimination of adverse events.

Background

The role of left atrial (LA) strain as an imaging biomarker in aortic stenosis is not well established. The aim of this study was to investigate the prognostic performance of phasic LA strain in relation to clinical and echocardiographic variables and N-terminal pro–B-type natriuretic peptide in asymptomatic and minimally symptomatic patients with moderate to severe aortic stenosis and left ventricular ejection fraction > 50%.

Methods

LA reservoir strain (LASr), LA conduit strain (LAScd), and LA contractile strain (LASct) were measured using speckle-tracking echocardiography. The primary outcome was a composite of all-cause mortality, heart failure hospitalization, progression to New York Heart Association functional class III or IV, acute coronary syndrome, or syncope. Secondary outcomes 1 and 2 comprised the same end points but excluded acute coronary syndrome and additionally syncope, respectively. The prognostic performance of phasic LA strain cutoffs was evaluated in competing risk analyses, aortic valve replacement being the competing risk.

Results

Among 173 patients (mean age, 69 ± 11 years; mean peak transaortic velocity, 4.0 ± 0.8 m/sec), median LASr, LAScd, and LASct were 27% (interquartile range [IQR], 22%-32%), 12% (IQR, 8%-15%), and 16% (IQR, 13%-18%), respectively. Over a median of 2.7 years (IQR, 1.4-4.6 years), the primary outcome and secondary outcomes 1 and 2 occurred in 66 (38%), 62 (36%), and 59 (34%) patients, respectively. LASr < 20%, LAScd < 6%, and LASct < 12% were identified as optimal cutoffs of the primary outcome. In competing risk analyses, progressing from echocardiographic to echocardiographic-clinical and combined models incorporating N-terminal pro–B-type natriuretic peptide, LA strain parameters outperformed other key echocardiographic variables and significantly predicted clinical outcomes. LASr < 20% was associated with the primary outcome and secondary outcome 1, LAScd < 6% with all clinical outcomes, and LASct < 12% with secondary outcome 2. LAScd < 6% had the highest specificity (95%) and positive predictive value (82%) for the primary outcome, and competing risk models incorporating LAScd < 6% had the best discriminative value.

Conclusions

In well-compensated patients with moderate to severe aortic stenosis and preserved left ventricular ejection fractions, LA strain was superior to other echocardiographic indices and incremental to N-terminal pro–B-type natriuretic peptide for risk stratification. LAScd < 6%, LASr < 20%, and LASct < 12% identified patients at higher risk for adverse outcomes.

Section snippets

Study Population

Participants were from the prospective, multicenter Singapore Assessment of Valvular Insufficiency and Obstruction Using Biomarkers (SAVIOUR) study.19 They had moderate or severe AS (peak transaortic jet velocity [Vmax] ≥ 3.0 m/sec or aortic valve area [AVA] by the continuity equation ≤ 1.2 cm2), no or minimal symptoms (New York Heart Association [NYHA] functional class I or II), LVEF ≥ 50%, and no more than moderate aortic or mitral regurgitation. Informed consent was obtained. The study

Results

Among 173 patients (age, 69 ± 11 years; 55% men; aortic Vmax, 404 ± 78 cm/sec; mean pressure gradient, 40 ± 17 mm Hg; indexed AVA, 0.56 ± 0.13 cm2/m2), median LA reservoir strain (LASr), LA conduit strain (LAScd), and LA contractile strain (LASct) were 27% (IQR, 22%-32%), 12% (IQR, 8%-15%), and 16% (IQR, 13%-18%), respectively. Baseline characteristics, echocardiographic parameters, and median biomarker levels by primary outcome are shown in Table 1. Over a median follow-up period of 2.7 years

Summary of Key Findings

We present compelling data supporting a role for LA strain in the prognostic evaluation of largely asymptomatic patients with moderate to severe AS and preserved LVEF (Graphical Abstract). In competing risk analyses, LA deformation indices consistently outperformed those of AS hemodynamics and LV myocardial response, including LV GLS, and were independent of established clinical risk factors and NT-proBNP, a widely applied guideline-endorsed biomarker,1 in predicting adverse outcomes. LAScd <

Conclusion

In largely asymptomatic patients with moderate or severe AS and preserved LVEFs, LA strain was a stronger prognosticator of adverse clinical outcomes than other key echocardiographic indices and offered additive predictive value to clinical risk markers and plasma NT-proBNP. LAScd < 6%, LASr < 20%, and LASct < 12% identified patients at higher risk for adverse outcomes.

Acknowledgments

The contributions of all clinical staff members, study coordinators, technicians, and patients who assisted with this study are duly acknowledged.

References (53)

  • M. Gomez Perez et al.

    Combined use of tissue Doppler imaging and natriuretic peptides as prognostic marker in asymptomatic aortic stenosis

    Int J Cardiol

    (2017)
  • J.S. Dahl et al.

    Assessment of subclinical left ventricular dysfunction in aortic stenosis

    JACC Cardiovasc Imaging

    (2019)
  • S. Levy-Neuman et al.

    The association between longitudinal strain at rest and stress and outcome in asymptomatic patients with moderate and severe aortic stenosis

    J Am Soc Echocardiogr

    (2019)
  • N. Thellier et al.

    Prognostic importance of left ventricular global longitudinal strain in patients with severe aortic stenosis and preserved ejection fraction

    J Am Soc Echocardiogr

    (2020)
  • K.K. Poh et al.

    Prognostication of valvular aortic stenosis using tissue Doppler echocardiography: underappreciated importance of late diastolic mitral annular velocity

    J Am Soc Echocardiogr

    (2008)
  • W. Hanif et al.

    Left atrial remodeling, hypertrophy, and fibrosis in mouse models of heart failure

    Cardiovasc Pathol

    (2017)
  • G. Benfari et al.

    Effects of aortic valve replacement on left ventricular diastolic function in patients with aortic valve stenosis

    Am J Cardiol

    (2019)
  • L. Thomas et al.

    Left atrial structure and function, and left ventricular diastolic dysfunction: JACC state-of-the-art review

    J Am Coll Cardiol

    (2019)
  • A. Singh et al.

    LA strain for categorization of LV diastolic dysfunction

    JACC Cardiovasc Imaging

    (2017)
  • D.A. Morris et al.

    Potential usefulness and clinical relevance of adding left atrial strain to left atrial volume index in the detection of left ventricular diastolic dysfunction

    JACC Cardiovasc Imaging

    (2018)
  • C.M. Bianco et al.

    Myocardial mechanics in patients with normal LVEF and diastolic dysfunction

    JACC Cardiovasc Imaging

    (2020)
  • K. O’Connor et al.

    Impact of aortic valve stenosis on left atrial phasic function

    Am J Cardiol

    (2010)
  • D. Genovese et al.

    Load dependency of left atrial strain in normal subjects

    J Am Soc Echocardiogr

    (2018)
  • P. Faggiano et al.

    Progression of aortic valve sclerosis to aortic stenosis

    Am J Cardiol

    (2003)
  • G. Strange et al.

    Poor long-term survival in patients with moderate aortic stenosis

    J Am Coll Cardiol

    (2019)
  • A. Coisne et al.

    Impact of moderate aortic stenosis on long-term clinical outcomes: a systematic review and meta-analysis

    JACC Cardiovasc Interv

    (2022)

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    This study was funded by the National Medical Research Council of Singapore (NMRC/CG/NUHCS/2010, NMRC/CG12Aug14, and NMRC/CGAug16C006), which was not involved in the conduct of the study.

    Dr Ewe has received personal fees from Medtronic, Edwards Lifesciences, and Abbott Medical, outside the submitted work. Dr Ding has received personal and speaker fees from GE and Phillips and nonfinancial support from Phillips, outside the submitted work; Dr Richards has received grants from the National Medical Research Council (NMRC) of Singapore; is a long-term collaborator with Roche Diagnostics, the provider of assays central to this submission; and has received support in kind, grants, and speaker’s honoraria from and participated on advisory boards for Roche Diagnostics. Dr Ling has received grants from the National Medical Research Council of Singapore, during the conduct of the study.

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    2022 by the American Society of Echocardiography.