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 Table of Contents  
REVIEW ARTICLE
Year : 2021  |  Volume : 5  |  Issue : 3  |  Page : 211-217

Role of Strain Imaging for Guiding Management of Valvular Heart Disease: Current Status


Department of Cardiology, CHL Hospitals, Indore, Madhya Pradesh, India

Date of Submission21-Feb-2021
Date of Acceptance23-Aug-2021
Date of Web Publication01-Dec-2021

Correspondence Address:
Dr. Atul Karande
3, Sainath Colony, Sector-B, Tilak Nagar, Indore -452 018, Madhya Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiae.jiae_6_21

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  Abstract 

Echocardiographic strain imaging allows more precise evaluation of cardiac function and provides new insights into the complex cardiac mechanics. Global longitudinal strain is found to be clinically useful in various valvular heart diseases. It provides additional diagnostic and prognostic information besides standard echocardiographic and clinical parameters. In this review, a summary of current clinical applications, limitations, and future of strain echocardiography in patients with valvular heart diseases is discussed.

Keywords: Global longitudinal strain, speckle tracking, strain, valvular disease


How to cite this article:
Karande A. Role of Strain Imaging for Guiding Management of Valvular Heart Disease: Current Status. J Indian Acad Echocardiogr Cardiovasc Imaging 2021;5:211-7

How to cite this URL:
Karande A. Role of Strain Imaging for Guiding Management of Valvular Heart Disease: Current Status. J Indian Acad Echocardiogr Cardiovasc Imaging [serial online] 2021 [cited 2022 Aug 12];5:211-7. Available from: https://www.jiaecho.org/text.asp?2021/5/3/211/331676


  Introduction Top


Valvular heart disease (VHD) is a major contributor to loss of physical function, quality of life, and longevity. The epidemiology of VHD varies substantially around the world, with a predominance of functional and degenerative disease in high-income countries, whereas there is still a large burden of rheumatic heart disease (RHD) in low- and middle-income countries. Contrary to popular belief, there is hardly any decline in RHD in the last 25 years, in low- and middle-income countries.[1] In VHD, clinical outcome depends on optimum assessment of risk and appropriate timing of intervention. Present guidelines advocate the use of left ventricular ejection fraction (LVEF) for decision-making regarding intervention.[2] However, over the last decade, strain imaging has emerged as an important parameter for the management of patients with VHD as it provides additional information useful for diagnostic and prognostic purposes.[3],[4],[5] In this article, we review present clinical applications, limitations, and future of strain echocardiography in the management of VHD.


  Evaluation of Cardiac Function in Valvular Heart Diseases Top


It is challenging to recognize early left ventricular (LV) systolic dysfunction in VHD. According to the current guidelines, in asymptomatic patients with severe valve disease, decision to intervene is based on a fall in LVEF to prevent irreversible LV damage.[2] Surgical intervention is indicated in asymptomatic patients with severe mitral regurgitation (MR) if LVEF ≤60% and with severe aortic disease (aortic regurgitation [AR] or aortic stenosis [AS]) at LVEF <50%. However, LVEF is a volume-based parameter without any consideration of complex myocardial mechanics. In patients of valve diseases, loading conditions are inherently altered, and LVEF which represents only relative volume change has an important limitation in the assessment of systolic function.

In regurgitant valvular diseases, LVEF is often exaggerated making it a poor indicator of LV systolic function.[6],[7] In mitral regurgitation (MR), LVEF estimation includes both aortic stroke volume and regurgitant volume; thus, LV systolic function is supernormal, at least during the early stages. LVEF can remain within normal limits for a long duration and may mask subtle early contractile dysfunction. Similarly, aortic stenosis (AS) causes concentric LV hypertrophy with reduction in cavity size; hence, LVEF can remain normal despite a decrease in myocardial shortening.[8] Therefore, in stenotic lesions also, EF can only detect LV systolic dysfunction at a later stage of disease when myocardial contractility has already become significantly impaired.

In this scenario, strain imaging may be of great value in detecting subtle early dysfunction and global longitudinal strain (GLS) is the earliest to be affected.[6],[7],[9] Initially, as LV systolic dysfunction sets in, increased circumferential strain compensates for reduced longitudinal strain so that LVEF remains within normal limit.[8] Therefore, identification of subclinical dysfunction by GLS is the most important part of deformation imaging in VHD.[3],[4],[5],[10],[11]


  Clinical Applications of Strain Echocardiography in Valve Diseases Top


Strain imaging can detect subclinical LV systolic dysfunction which might be helpful in determining the timing of interventions in VHD. Robust data are available on aortic and mitral valvular diseases, but studies on tricuspid and pulmonary valve diseases are limited.

Aortic stenosis

Natural history of asymptomatic severe AS is unpredictable and variable. In AS, myocardial fibrosis is one of the main processes determining the LV decompensation and the progression to the development of symptoms, heart failure, and adverse events. According to current guidelines, early elective surgery is indicated in asymptomatic patients with depressed LV function (EF <50%) not due to other causes and in patients who develop symptoms during exercise testing.

Abnormal longitudinal LV systolic function, manifesting as impaired LVGLS, is one of the predictors of symptom development and adverse outcomes in asymptomatic patients with severe AS. In AS, GLS goes on worsening with the severity of lesion, even though LVEF can remain normal or supernormal for a long time. [Video 1] and [Figure 1].[12] Among the subgroups, GLS is more impaired in patients with severe AS and low flow than those with normal flow and patients with low flow/high gradient AS have a more impaired GLS than those with normal flow/high gradient.[12] GLS is one of the strong predictors of all-cause mortality independent of stenosis severity and LVEF.[12],[13],[14],[15] In symptomatic patients undergoing aortic valve replacement (AVR), preoperative GLS is of incremental prognostic value in addition to age, LV mass, and left atrial (LA) volume.[3]
Figure 1: Markedly impaired global longitudinal strain (-11.9%) in a patient of severe aortic stenosis and maintained ejection fraction (Video 1)

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[Additional file 1]

Video 1: Markedly impaired left ventricular global longitudinal strain [Figure 1] in a patient of severe aortic stenosis and maintained ejection fraction.

In asymptomatic patients of severe AS and preserved LVEF, if −18.2% is taken as cutoff, event rate (symptoms and need for AVR) is higher in impaired GLS patients.[10] Similarly, 5-year event-free survival improves if GLS is more than −17% [Figure 2]a.[15] In a recent large study, a GLS worse than −14.7% predicted a 2.5-fold increase in mortality.[16] Hence, if GLS is impaired in asymptomatic severe AS, patients can be referred for earlier intervention than recommended by current guidelines.[2] The Heart Valve Clinic International Database group has included GLS into algorithm for decision-making in asymptomatic severe AS. According to them, intervention may be done in patients with asymptomatic severe AS if GLS is <−16.0% and other risk factors are present such as high calcium score on computed tomography (CT) and myocardial fibrosis on cardiac magnetic resonance imaging (MRI).[17] Recently, Dahl et al. have also recommended a similar approach [Figure 3].[18]
Figure 2: Normogram of estimated risk of death at 5 years for left ventricular global longitudinal strain (GLS) in valve diseases: (a) Aortic stenosis. Based on data from Huded CP, et al. J Am Heart Assoc. 2018;7:pii, e007880. (b) Aortic regurgitation. Reproduced with permission from Alashi A, et al. JACC Cardiovasc Imaging. 2018;11:673–82. (c) Mitral regurgitation. Reproduced with permission from Mentias A, et al. J Am Coll Cardiol. 2016;68:1974–86.The GLS value where the risk of death continuously increased is marked in every group by vertical orange dashed line. AVR: Aortic valve replacement, LV-GLS: Left ventricular global longitudinal strain

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Figure 3: Proposed algorithm for the management of patients with asymptomatic severe aortic stenosis. Reproduced with permission from Dahl JS, et al. JACC Cardiovasc Imaging, 2019;12:163–71. *The presence of important late gadolinium enhancement, delayed native T1, or elevated extracellular volume in cardiac magnetic resonance. Only if there is no other current guidelines indication for aortic valve intervention. LOE = Level of Evidence, AS: Aortic Stenosis

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Cardiac MRI has the ability to characterize the pattern and volume of myocardial fibrosis.[19],[20] T1 mapping of extracellular volume provides an estimate of diffuse fibrosis specific to pressure-overload cardiomyopathies. Other studies indicate that the presence of mid wall fibrosis is more specific to AS rather than to ischemic heart disease and is a more powerful predictor of cardiac events.

Aortic regurgitation

Asymptomatic patients of severe aortic regurgitation (AR) have better GLS than those with symptomatic severe AR. According to the current guidelines, early elective surgery is indicated in asymptomatic patients with LVEF <50% and/or LV enlargement with an LV end-diastolic diameter >70 mm or left ventricular end-systolic diameter >25 mm/m2. Impaired GLS with −19.3% as cutoff can be considered to pick up asymptomatic patients who will need AVR during follow-up.[21] In another study, it was concluded that in asymptomatic AR, the mortality continuously increased as GLS decreased below −19% [Figure 2]b.[4] Classification of mortality risk improves if GLS is included in determining the risk of death. In symptomatic patients referred for AVR, mortality is high if preoperative GLS is <−19%.[22]

Mitral regurgitation

Primary and secondary MR behave as two different entities. In symptomatic patients or those with overt LV systolic dysfunction, the decision about mitral valve surgical timing is already clear. Currently, in asymptomatic patients with severe primary MR, surgery is indicated in the presence of LVEF ≤60%, LV end-systolic diameter ≥45 mm, atrial fibrillation, and/or a systolic pulmonary pressure of ≥50 mmHg at rest. In patients of severe MR referred for mitral valve surgery, preoperative GLS <−18.1% was associated with poor outcome, and it had incremental predictive value over conventional clinical and echocardiographic risk factors.[5],[23] Similarly, in asymptomatic severe MR patients with preserved LVEF who underwent mitral valve surgery, a combination of abnormal brain natriuretic peptide (BNP) and impaired LV-GLS was associated with abnormal postoperative LVEF and increased long-term mortality. One large study showed improvement in all-cause mortality after mitral valve surgery in patients of asymptomatic severe MR if GLS was <–21% [Figure 2]c.[24] In these studies, the GLS cutoff values reported were higher which indicates that in patients of primary MR, GLS values that are otherwise considered normal may also have poor outcome.

In contrast to primary MR, there is currently no evidence that a reduction of secondary MR improves survival. Robust data evaluating the clinical value of GLS in secondary MR are lacking. A retrospective study of 650 severe MR patients concluded that GLS <−7.0% was associated with higher mortality, whereas there was no association of LVEF with mortality.[25] In comparison to primary MR, the lower GLS found in this study was due to high-risk patients that were investigated, many of them had advanced heart failure.

Mitral stenosis and tricuspid and pulmonary valve diseases

Limited studies are available evaluating clinical utility of GLS in mitral stenosis, and tricuspid and pulmonary valve diseases. Severe mitral stenosis is associated with impaired GLS which is related to the severity of mitral stenosis.[26],[27] Sengupta et al. showed that after balloon mitral commissurotomy, strain values improved within 72 h. In these patients, the impaired LV deformation was due to reduced LV diastolic filling without much contribution of irreversible myocardial structural damage.[26]

In significant tricuspid regurgitation, RV free wall GLS of <−23% was associated with poor outcome. In this regard, prognostic value of RV GLS is beyond conventional echocardiographic parameters of RV systolic function such as tricuspid annular plane systolic excursion and fractional area change.[28]

In pulmonary valve disease patients referred for percutaneous pulmonary valve implantation, preprocedural RV GLS can predict the improvement of exercise capacity after procedure.[29]


  Limitations of Strain Echocardiography in Valve Diseases Top


Variable global longitudinal strain cutoffs

Various studies evaluating the utility of GLS in various VHDs have proposed different cutoffs for each VHD [Figure 2]. Furthermore, for the same VHD, cutoffs are variable in different studies. This is the main reason why it has been difficult to include strain into decision-making guidelines.

Technical factors such as intervendor variability also contribute to variability. Different vendors use different postprocessing algorithms and strain definitions for measuring strain. Vendors use either full-wall strain or mid wall or endocardial strain and this is an important reason for differences in strain measurements among various vendors.[30]

Effect of load on strain

Experimental studies indicate that increase in the afterload decreases the strain while increasing preload increases the strain.[31],[32],[33] In experiments models which created effects of progressive AS with chronic increase in afterload, all strain components were found to decrease, with prominent effect on GLS.[34] As against this, transcatheter AVR which leads to sudden decrease in afterload results in rapid increase in GLS.[35] Studies show that, among all determinant of overall cardiac performance, afterload is the dominant factor which affects the GLS.[31] These results indicate that strain is affected more by afterload than contractility.

Tilt-table test studies show that preload reduction in upright position leads to a significant acute decrease in GLS compared to supine position.[36] This confirms the Frank-Starling concept that myocardial contraction can be increased by prestretching and indicates that GLS depends on preload. In patients of valvular regurgitation when there is chronic increase in preload, a biphasic behavior of GLS is seen. Initially, when myocardial contractility is still maintained, GLS is increased.[6],[7],[24] Hence, at this stage, strain values indicate volume overload rather than altered contractility. Later, with the adaptive remodeling of the ventricle, GLS becomes normal and eventually decreases due to impairment of myocardial contractility.

Effect of chamber remodeling on strain

Chronic pressure or volume overload leads to chamber remodeling, and it additionally influences GLS. In AS patients, chronic pressure overload causes LV hypertrophy with decrease in cavity size which maintains wall stress within normal limits. As a result of both these alterations, initially, LV EF increases and it is maintained for a long period despite a reduction in GLS[8] [Video 1] and [Figure 1]. Experimental studies have shown that, in these patients with chronically increased LV afterload and maintained LVEF, decrease in GLS is mainly due to hypertrophy rather than impaired contractility and pressure overload. Hence, the deformation is predominantly affected by hypertrophy (62%) and to a lesser extent by impaired contractility and afterload (38%) [Figure 4]a. At a later stage in patients of valvular stenosis and chronic pressure overload, impaired GLS is due to altered contractility secondary to LV myocardial fibrosis [Figure 4]b.[34]
Figure 4: Relative contribution of various factors to alterations in global longitudinal strain in diseases with chronically increased afterload and hypertrophy- (a) at early-stage, and (b) at advanced stage. Thus, contractile state of the myocardium is hard to establish from a single strain measurement alone

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In patients of valvular regurgitation, volume overload over a long time causes chamber enlargement and augmentation of stroke volume. GLS increases with increase in stroke volume but decreases if the chamber enlargement is not accompanied by an increase in stroke volume.[7] Thus, GLS is determined by an interplay between stroke volume, chamber size, and the myocardial contractility and not directly by regurgitation itself [Figure 5]a. Therefore, in the early stages of valvular regurgitation, increased stroke volume increases GLS.[6],[7],[24] Later on, wall stress increases due to exhaustion of all compensatory mechanisms, and myocardium is irreversibly damaged resulting in impaired contractility. At this stage, decreased contractility mainly contributes to impaired GLS [Figure 5]b.[6],[7]
Figure 5: (a)Factors contributing to alterations in global longitudinal strain in diseases with chronic increase in preload. (b) Biphasic behavior of myocardial strain in patients with increased preload. In the early phase of valve regurgitation, strain values increase due to increased stroke volume. In advanced disease, irreversible changes in the myocardium result in the development of contractile dysfunction and impaired deformation. GLS: Global longitudinal strain

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  Future of Strain Echocardiography in Valve Diseases Top


Emerging evidences suggests that strain imaging will soon become an integral part of evaluation of VHDs. Clinical studies have strongly indicated that strain imaging gives prognostic information in addition to routine clinical and echocardiographic parameters. However before its wider implementation in clinical practice, there are some limitations that need to be addressed.

As discussed above, several observational studies have shown that strain imaging can be included as an additional parameter for taking decisions regarding early intervention in asymptomatic VHD patients. However, large randomized control trials are needed to conclusively prove that such strain-guided management does indeed lead to improved clinical outcomes.

Another issue with strain imaging is variable GLS cutoffs. For using strain imaging for clinical decision making, we need disease-specific cutoffs. Due to the efforts of the European Association of Cardiovascular Imaging, American Society of Echocardiography and Industry Task Force on strain standardization, intervendor variability has been reduced to a great extent.[30],[37] However, in recent comparative studies of vendors, a moderate bias still remains.[38],[39] The evidence favors measurement of full wall strain, but still there is no uniformity regarding the layer selection for estimation of LV strain.[39],[40]

To overcome the dependency of strain on loading conditions and geometry, various authors have proposed different approaches. One of the sensitive methods in regurgitative lesions could be to correct myocardial strain for changes in geometry.[6],[7],[9] In patients of AR and control group, when absolute GLS values were compared with the GLS values normalized to LV end-diastolic volume, remarkably less overlap was observed.[6],[9]

Similarly, some studies have shown that in AS, to segregate the effect of myocardial contractility and afterload, GLS should always be measured along with end-systolic wall stress.[41] The myocardial work estimation is a relatively new noninvasive concept which integrates strain obtained by speckle tracking with afterload estimated by LV pressure, i.e., blood pressure [Figure 6].[42] In AS, myocardial work can be reliably estimated by the adding mean aortic gradient to systolic blood pressure.[43] LV stress–strain loop areas have been suggested as an index of myocardial work where wall stress can be estimated by integrating measurement of wall thickness, radius of curvature, and blood pressure [Figure 7].[44] However, we need further large trials to establish that these proposed approaches can yield better prognostic parameters.
Figure 6: (a) Representative traces showing pressure–strain loops derived from estimated left ventricular (LV) pressure and strain using speckle-tracking echocardiography. (b) The myocardial work bull's eye showing work done by various segments. AVC: Aortic valve closure, AVO: Aortic valve opening, LVP: Left ventricular pressure, MVC: Mitral valve closure, MVO: Mitral valve opening

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Figure 7: Schematic diagram showing steps involved in the calculation of segmental left ventricular (LV) stress-strain loop area. Segmental strain curves are imported from speckle-tracking software. LV pressure, segmental wall thickness, and curvature are used to calculate segmental wall stress. Finally, segmental stress-strain loops are constructed and the loop area is used as a measure of regional work load. Reproduced with permission from Cvijic M et al. Eur Heart J Cardiovasc Imaging. 2018;19:941–9. LVP: Left ventricular pressure

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  Conclusion Top


Strain imaging is gradually becoming a part of comprehensive evaluation of VHDs. It can identify patients who are likely to develop symptoms, can predict poor survival, and likely to become a part of algorithms for taking decisions in the management of VHDs. As besides contractility, strain is also affected by loading conditions and chamber geometry, large trials are needed to establish the role of myocardial work and stress–strain loop areas.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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