Myocardial Stiffness by Intrinsic Cardiac Elastography in Patients with Amyloidosis: Comparison with Chamber Stiffness and Global Longitudinal Strain

doi:10.1016/j.echo.2019.04.418

Journal of the American Society of Echocardiography

Volume 32, Issue 8, August 2019, Pages 958-968.e4

https://doi.org/10.1016/j.echo.2019.04.418 Get rights and content

Highlights

•
A novel ultrahigh frame rate, tissue Doppler-based cardiac elastography method was developed.
•
This method was applied in patients with cardiac amyloidosis.
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Findings by elastography correlated with cardiac functional and structural derangements.
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These measurements were incremental to known echocardiographic predictors of outcomes.

Background

The aim of this study was to test the hypothesis that intrinsic cardiac elastography can detect diastolic tissue abnormalities produced by cardiac amyloid infiltration and that measurements may have incremental value beyond traditional echocardiographic measures. The specific aims were (1) to evaluate the relationship between left ventricular myocardial stiffness (by elastography) and measures of diastolic chamber stiffness and systolic strain in patients with amyloidosis and (2) to compare their prognostic potential.

Methods

We prospectively studied 67 patients with amyloidosis (cardiac amyloidosis, n = 48; noncardiac amyloidosis, n = 19) and 40 normal subjects. Patients underwent comprehensive echocardiography including measurement of left ventricular global longitudinal strain (GLS) by speckle-tracking. Intrinsic velocity propagation of myocardial stretch (iVP), a direct measure of myocardial elasticity, was quantified using intrinsic cardiac elastography. Chamber stiffness was evaluated from the end-diastolic pressure-volume relationships (P = αV^β). The major end point at follow-up was the composite of death, cardiac hospitalization, worsening heart failure, and stroke.

Results

The iVP of myocardial stretch was highest in patients with cardiac amyloidosis compared with those with noncardiac amyloidosis and normal subjects (3.2 ± 1.0, 1.8 ± 0.4, and 1.6 ± 0.2 m/sec, respectively; P < .0001) and correlated with chamber stiffness, function, and structure (β coefficient, operating chamber stiffness, GLS, wall thickness; P ≤ .001 for all). At follow-up (median, 2.6 years), measures of left ventricular and myocardial stiffness, GLS, diastolic dysfunction grade, and N-terminal pro–brain natriuretic peptide were associated with excess events. At multivariate analysis, iVP of myocardial stretch remained an independent predictor of adverse events, incremental to GLS and N-terminal pro–brain natriuretic peptide.

Conclusions

Measurements by cardiac elastography correlate with functional and structural derangements produced by cardiac amyloid infiltration but provide unique information that is incremental to conventional echocardiography.

Section snippets

Methods

The protocol was approved by the institutional review board at our institution and complied with the Declaration of Helsinki; written informed consent was obtained from each subject. We studied consecutive patients with biopsy-proven systemic amyloidosis referred for echocardiographic evaluation in various stages of their disease. A control group was recruited from healthy volunteers or patients referred to the echocardiography laboratory and found to have normal results on echocardiography.

Results

A total of 120 subjects were enrolled for this study; of these, 13 were excluded (concomitant moderate to severe valvular heart disease in three, atrial fibrillation in two, amyloidosis other than amyloid light-chain [AL] or amyloid transthyretin [ATTR] amyloidosis in three, incomplete iVP measurement in five). The final cohort included 107 subjects: 67 patients with systemic amyloidosis (88% with AL amyloidosis, 12% with ATTR amyloidosis) and 40 normal subjects. Of the 67 patients, 48 had

Discussion

In this study we demonstrate that intrinsic cardiac elastography can detect presence of increased LV/myocardial stiffening in patients with CA as confirmed by an independent method (EDPVR), and measures of myocardial elasticity had strong predictive value incremental to functional assessment by conventional echocardiography including strain imaging.

Conclusion

This study demonstrates that measurements by cardiac elastography correlate with functional and structural derangements produced by cardiac amyloid infiltration but provide unique information that is incremental to functional assessment by echocardiography including speckle-tracking strain imaging. Further studies are needed to fully understand the role of this novel measurement for specific clinical applications.

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The advent of high–frame rate imaging in ultrasound allowed the development of shear wave elastography as a noninvasive alternative for myocardial stiffness assessment. It measures mechanical waves propagating along the cardiac wall with speeds that are related to stiffness. The use of cardiac shear wave elastography in clinical studies is increasing, but a proper understanding of the different factors that affect wave propagation is required to correctly interpret results because of the heart’s thin-walled geometry and intricate material properties. The aims of this review are to give an overview of the general concepts in cardiac shear wave elastography and to discuss in depth the effects of age, hemodynamic loading, cardiac morphology, fiber architecture, contractility, viscoelasticity, and system-dependent factors on the measurements, with a focus on clinical application. It also describes how these factors should be considered during acquisition, analysis, and reporting to ensure an accurate, robust, and reproducible measurement of the shear wave.
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MWV estimation during atrial kick is feasible and demonstrates higher velocities in the lateral walls, compared with septal walls. The authors propose indicators for quality assessment of the mechanical wave slope as an aid for achieving consistent measurements. The discrimination between healthy subjects and patients with AS was best for the aortic valve closure mechanical waves. (Ultrasonic Markers for Myocardial Fibrosis and Prognosis in Aortic Stenosis; NCT03422770)
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MS was measured to be significantly higher in CA patients using both ARFI and NSW imaging. Together, these methods have potential utility to aid in clinical diagnosis of diastolic dysfunction and infiltrative cardiomyopathies.
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: This work was supported in part by a Prospective Research Award (to Dr. Cristina Pislaru) from the Mayo Clinic.

: Conflicts of Interest: None.

View full text

2019 by the American Society of Echocardiography.

Clinical InvestigationNew Cardiac Ultrasound TechnologiesMyocardial Stiffness by Intrinsic Cardiac Elastography in Patients with Amyloidosis: Comparison with Chamber Stiffness and Global Longitudinal Strain

Highlights

Background

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

Conclusion

J Am Coll Cardiol

J Am Coll Cardiol

J Am Soc Echocardiogr

Am J Cardiol

J Am Coll Cardiol

JACC Cardiovasc Imaging

J Am Soc Echocardiogr

J Am Soc Echocardiogr

JACC Cardiovasc Imaging

J Am Coll Cardiol

J Am Soc Echocardiogr

Cardiovasc Pathol

J Am Soc Echocardiogr

Immunoglobulin light chain amyloidosis: 2016 update on diagnosis, prognosis, and treatment

Am J Hematol

Light-chain cardiac amyloidosis: strategies to promote early diagnosis and cardiac response

Heart

Transthyretin (TTR) cardiac amyloidosis

Circulation

Longitudinal myocardial function assessed by tissue velocity, strain, and strain rate tissue Doppler echocardiography in patients with AL (primary) cardiac amyloidosis

Circulation

Relative apical sparing of longitudinal strain using two-dimensional speckle-tracking echocardiography is both sensitive and specific for the diagnosis of cardiac amyloidosis

Heart

Correlation of histomorphological pattern of cardiac amyloid deposition with amyloid type: a histological and proteomic analysis of 108 cases

Histopathology

Clinical Investigation
New Cardiac Ultrasound Technologies
Myocardial Stiffness by Intrinsic Cardiac Elastography in Patients with Amyloidosis: Comparison with Chamber Stiffness and Global Longitudinal Strain