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 Table of Contents  
Year : 2023  |  Volume : 7  |  Issue : 2  |  Page : 93-100

Utility of Global Longitudinal Strain in Mitral Regurgitation: A Systematic Review

1 Department of Cardiology, CMC, Vellore, Tamil Nadu, India
2 Department of Community Medicine, CMC, Vellore, Tamil Nadu, India

Date of Submission08-Jun-2023
Date of Decision01-Aug-2023
Date of Acceptance03-Aug-2023
Date of Web Publication30-Aug-2023

Correspondence Address:
Jesu Krupa
Department of Cardiology, CMC, Vellore, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jiae.jiae_33_23

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Background: The assessment of myocardial function is important in both primary and secondary mitral regurgitation (MR), to determine the timing of interventions and to predict outcomes. Ejection fraction is relied on for clinical decisions, even though, it is well understood that it does not reflect myocardial function. Global longitudinal strain (GLS) is a promising parameter that correlates well with outcomes postinterventions. In this review, we aimed to determine the utility of GLS in both primary and secondary MR in predicting clinical outcomes. We also aimed to determine the GLS cutoff at which clinical decisions can be made. Methods: We conducted a systematic review of the literature regarding the use of GLS as a predictor of left ventricular (LV) function. We searched PubMed and Embase for relevant articles and identified 141 articles after removing duplicates. We screened titles and abstracts to identify 28 relevant articles from which data were extracted. Results: In 16 of the 28 studies, patients had primary MR mostly of degenerative etiology and the LV GLS cutoff for events ranged from −17.2% to −21%. In 10 studies, patients with secondary MR were included, and a cutoff ranging from −7%− to −9% was most often reported except for one study that reported-16.3%, as it included patients with atrial functional MR. Conclusion: GLS assesses LV dysfunction and is a good predictor of clinical and echocardiographic outcomes postinterventions. Values lower than the cutoff value of −17.2% to −21% in primary MR and −7% to −9% in secondary MR are associated with poorer outcomes. These findings suggest that the use of GLS as a routine assessment in patients with significant MR may be appropriate for both clinical decision-making and prognostication.

Keywords: Global longitudinal strain, left ventricular function, mitral regurgitation

How to cite this article:
Krupa J, Lall D. Utility of Global Longitudinal Strain in Mitral Regurgitation: A Systematic Review. J Indian Acad Echocardiogr Cardiovasc Imaging 2023;7:93-100

How to cite this URL:
Krupa J, Lall D. Utility of Global Longitudinal Strain in Mitral Regurgitation: A Systematic Review. J Indian Acad Echocardiogr Cardiovasc Imaging [serial online] 2023 [cited 2023 Oct 4];7:93-100. Available from: https://jiaecho.org/text.asp?2023/7/2/93/384774

  Introduction Top

Management decisions for intervention in severe mitral regurgitation (MR) depend on the symptomatic status of the patient, left ventricular (LV) dimensions, and ejection fraction (EF).[1] It is well understood that load dependence, measurement error, and observer variability render LVEF a poor measure of LV systolic function. In addition, LVEF, which is calculated from end-diastolic and end-systolic chamber volumes, is a measure of chamber function and not of myocardial function.[2] Further, in severe MR, there is a tendency to overestimate the LV function by EF since there is an increase in preload and a reduced afterload due to the LV unloading into a low-pressure left atrium.[3],[4] Hence, an LVEF cutoff of 60%, higher than normal, is recommended for surgical decision-making.[5] LV end-systolic dimension (ESD) is another measure at a cutoff of 40 mm that is often used to decide on surgery. LV ESD is relatively independent of preload, and it reflects contractility, afterload, and remodeling. However, it varies with body size and there are racial differences. Hence, both LVEF and LVESD have limitations for decision-making in severe MR.

There have been vast improvements in mitral valve repair techniques for mitral valve prolapse (MVP) as well as an improved awareness leading to early detection of MVP.[6] Corrective surgery is often conducted even before the onset of LV dysfunction and overt symptoms. However, in the Indian context, most MR is of rheumatic origin and patients still undergo mitral valve replacement instead of repair. In either case, a robust estimation of LV function is required to decide on management.

Global longitudinal strain (GLS) is a measure of the longitudinal function of the myocardium which reflects a change in the length of the myocardial fiber in relation to its initial length.[7] GLS is less load-dependent as compared to EF and has been shown in various conditions to be impaired even before a reduction in EF.[8] Many studies have evaluated the prognostic advantage of GLS and recommend the use of GLS for management decisions.[9],[10]

However, its utility in various groups of MR by etiology and severity remains unclear. Therefore, in this systematic review, we included all studies with different groups of MR, where the prognostic utility of GLS has been explored. We present the current evidence for GLS as a predictive tool in primary and secondary MR for clinical and echocardiographic outcomes. The question of how to detect subclinical LV dysfunction early or predict its occurrence postoperatively remains clinically significant for planning early MV interventions, especially in primary MR [Figure 1].
Figure 1: Example of a patient with severe mitral valve regurgitation (MR) and normal global longitudinal strain value. (a-c) Two-dimensional apical views (left to right apical three-chamber view, apical two-chamber view and apical four-chamber view) with strain overlay and corresponding strain curves underneath. (d) Bull's eye pattern of regional strain values. (e) Colour Doppler image illustrating the severe MR[11]

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  Methods Top

We conducted a systematic review of the literature regarding the use of GLS as a predictor of LV function. We searched PubMed and Embase for relevant articles. The search strategy included key terms and MeSH terms for PubMed (“Global longitudinal strain” OR “left ventricular strain”) AND (“mitral valve insufficiency” OR “mitral regurgitation”). The same key terms were modified for Embase. A total of 141 articles were identified after the removal of duplicates. Abstract screening for relevance to the research question was done and 28 articles were finally selected for review. We used the PICO framework to include all studies reporting original research, not limited by age group or study design. The primary outcomes included were both clinical and echocardiographic. Clinical outcomes reported were all-cause mortality, symptomatic improvement in New York Heart Association (NYHA) class, and exercise tolerance measured by metabolic equivalents, and the echocardiographic outcomes were LVEF and LVESD. All the studies reported the prognostic utility of GLS in different subgroups of patients with MR of varying etiology, before or after an intervention. Most studies reported a cutoff value for GLS that correlated with the outcome measured. Some studies also reported the sensitivity and specificity of the cutoff value proposed. We excluded studies that used GLS as an outcome measure in the evaluation of different treatment modalities and those that reported mean GLS as an outcome. The data were extracted from individual studies and synthesized to draw meaningful conclusions.

Data synthesis and quality appraisal

We synthesized the data in subgroups of MR by etiology and by surgical repair or replacement. In each subgroup, we assessed the prognostic value of GLS as reported and the GLS cutoff value associated with the outcome studied. We synthesized clinical and echocardiographic outcomes in each subgroup and reported the prognostic value of GLS.

The JBI tool for quality appraisal of cross-sectional analytic studies[12] was used since the observational cohort design was the most often used study design. Most studies were of good quality; however, few studies were limited by the sample size included.

  Results Top

A total of 141 articles were identified after the removal of duplicates from the search. Abstract and title screening was done to exclude a total of 112 articles [Figure 2]. Further, one article was excluded as it was not in English. The data were extracted from 28 articles that were finally included and are reported below. We first present the description of the studies included in terms of the year it was reported, study design sample size, age, gender composition of the sampled patients, and duration of follow-up. Next, we present the primary outcome, estimated prognostic utility of GLS reported, and its sensitivity/specificity if reported in the subgroups of primary and secondary MR.
Figure 2: PRISMA flowchart

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Most studies included were designed as observational cohorts, either prospective or retrospective. Sample sizes in the studies included ranged from 32 to 737 [Table 1]. Most of the study participants were in the elderly age group with a reported mean age of >65 years and were predominantly males. Of the 28 studies included, 15 studies were conducted in patients with primary MR and the remaining studies were in patients with secondary MR. Patients in most studies underwent interventions that were mostly surgical mitral valve repair but also included replacement and few transcatheter edge-to-edge repairs.
Table 1: Details of studies included in the review

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In 16 studies, the inclusion criteria was primary MR mostly of degenerative etiology and the LV GLS cutoff for events ranged from −17.2% to −21% [Table 2]. The main outcomes studied were mortality, postoperative LVEF after valve repair or replacement, and exercise tolerance. All studies reported a good correlation between GLS and the postoperative outcomes, except for one study.[18] In 10 studies of secondary MR, a cutoff ranging from −7% to −9% was reported. One study reported-16.3% as the cutoff, for patients with atrial functional MR.[13] Only 2 studies included both primary and secondary MR, of which one reported a cutoff of −14.5% for patients with degenerative MR (primary MR).[19] Most echocardiographic studies were done on General Electric (GE) systems, some were done on Philips machines, and few were done on Seimens systems. GE EchoPAC software (EchoPAC GE Medical Systems, Horten, Norway) was used for analysis in most of the studies. Few studies were done before 2015 before the standardization of GLS across vendors and this may explain some of the variations in cutoffs.
Table 2: Reported global longitudinal strain cutoff and prognostic utility according to the subgroup studied

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In the 16 studies that reported outcomes in primary MR, most underwent mitral valve repair. Both repair and replacement surgeries had findings that were comparable concerning GLS and the outcomes. Most studies used an echocardiographic outcome of LVEF, few studies also included LV and left atrial (LA) remodeling [Table 2]. The clinical outcomes studied included all-cause mortality (in four studies), cardiac event-free survival (in one study), and exercise tolerance (in one study). The cutoff for GLS that was associated with poorer outcomes ranged from −17.7% to −21.7%, except for one study that reported-11.91% ± 4.22%[21] [Table 2]. This study by Singh et al. was conducted in India, and all patients were in NYHA class II to III suggestive of more severe disease at initial presentation. Most studies evaluated GLS, but few studies included exercise and B-type natriuretic peptide (BNP) to add incremental value to prognostication.

In the 10 studies with secondary MR, the clinical outcomes measured were mainly all-cause mortality and cardiac events. Only one study reported an echocardiographic outcome of LV remodeling.[20] One study did not report any association of GLS with all-cause mortality, however, the mean GLS reported in the tertile with the poorest outcomes was −8.4%.[18]

  Discussion Top

In this systematic review, we found that LV GLS is a good predictor of clinical and echocardiographic outcomes in patients with primary MR undergoing mitral valve interventions and the cut-off value ranged from −17.2% to −21.0%. In secondary MR, most studies reported a good correlation of LV GLS with outcomes except for the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial.[18] In secondary MR, the GLS cut-off ranged from −7% to −9.2% and was predictive of mortality and poorer outcomes, irrespective of the type of intervention. The findings have implications for determining the optimal time for intervention as well as for predicting outcomes for informed decision-making. A few studies also reported incremental benefits of parameters such as exercise capacity and BNP that may further refine the utility of GLS in MR.

Left ventricular global longitudinal strain in primary mitral regurgitation

Preoperative assessment of myocardial function in primary MR has become increasingly important, especially since it is predictive of short and long-term postoperative echocardiographic and clinical outcomes.[41] LVEF and LV dimensions are currently used to decide on the optimal timing for surgery. However, GLS assesses LV function more accurately and hence, is useful to detect subclinical LV dysfunction.[9] With an improvement in surgical techniques and interventions, the aim is early detection of contractile dysfunction and early intervention in asymptomatic patients with severe MR. The estimation of GLS can improve decision-making for the timing of surgery in these patients that are asymptomatic and detected early. In patients that are symptomatic and candidates for surgery, GLS has a role to play in predicting postoperative LV dysfunction.

Most patients in the studies included in this review were older, had degenerative MR, and underwent mitral valve repair. There were few studies, from India, that included a small number of patients with rheumatic etiology that underwent mitral valve replacement. The utility of GLS in rheumatic etiology and in younger adults needs further exploration, especially in India.

Postoperative LV function may also be influenced by the type of surgery such as repair or replacement, length of cardiopulmonary bypass, specific surgical techniques such as chordal sparing MVR, the experience of the surgeon, caseload of the center, and myocardial protection measures. Therefore, while studying LV dysfunction as a predictive outcome, these factors should be taken into consideration.

There is a variability in the cutoff values that different studies have proposed. This range may be due to various reasons such as the studies were done on different vendors, with varying software versions, and at different time points. It is also to be noted that the normal value of GLS for a given individual has a wide range; for example, in men, it is known to range between −17.0% and −24%. Further, there is variation in the normal values by gender and race.[42] Hence, it may be more useful to compare GLS values in a given patient serially against their initial assessment, rather than with a normal reference value. A change in GLS values on serial follow-up such as for chemotherapy-related cardiotoxicity is known to be useful.[43]

Left ventricular global longitudinal strain in secondary mitral regurgitation

The main value of GLS estimation in secondary MR is for prognostication. However, the COAPT trial with a large sample of patients did not show any association of GLS with postintervention outcomes. Further exploration within specific subsets of patients may be required to understand its utility, for example, in atrial functional MR, ischemic MR, disproportionate, and proportionate MR.

Future directions

A limitation of GLS in MR at present is that there is no evidence from a randomized prospective trial that demonstrates the value of GLS-guided management in the improvement of clinical outcomes. Trials that evaluate clinical outcomes in patients assessed by GLS compared to those assessed by conventional methods would add to the evidence.

While GLS estimation correlates well with both clinical and echocardiographic outcomes, there is scope to further refine the measurement. The studies by Lancellotti et al.[39] and Magne et al.[33] found that exercise stress-induced change in GLS ≥−2% in primary MR was predictive of outcomes. The same was also noted in secondary MR by De Luca et al.[25] while using dobutamine stress echocardiography. Singh et al. showed that BNP estimation with GLS had an incremental value as compared to an estimation of only GLS.[21]

Some studies also report that assessment of myocardial disease in valvular heart disease may be further refined using novel cardiac magnetic resonance imaging biomarkers such as native T1 mapping, extracellular volume, and late gadolinium enhancement.[44] Echocardiographic biomarkers such as LA strain, LV strain, and LV myocardial work indices can also enhance the assessment of myocardial disease.

  Conclusion Top

GLS assesses LV function and is a good predictor of clinical and echocardiographic outcomes postintervention. Values lower than the cutoff value of −17.2%–21% in primary MR and −7%–−9% in secondary MR are associated with poorer outcomes. Serial measurements of GLS in the same patient may be useful in clinical decision-making for surgery and interventions. The utility of GLS can be enhanced by adding parameters such as stress, exercise-induced change in GLS, and BNP. Based on the evidence presented in this review, it may be appropriate for GLS estimation to become a part of routine assessment for myocardial function in patients with significant MR.

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Conflicts of interest

There are no conflicts of interest.

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  [Table 1], [Table 2]


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