|Year : 2023 | Volume
| Issue : 2 | Page : 109-120
Strain Imaging in Aortic Stenosis
Shanmugasundaram Somasundaram, U Ilayaraja, K Rajeswari
Department of Cardiology, Billroth Hospitals, Chennai, Tamil Nadu, India
|Date of Submission||10-Apr-2023|
|Date of Decision||03-Jun-2023|
|Date of Acceptance||06-Jun-2023|
|Date of Web Publication||30-Aug-2023|
Billroth Hospitals, Chennai, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Although aortic stenosis (AS) is a disease of poor outcomes, timely aortic valve replacement [AVR -surgical AVR (SAVR) or transcatheter AVR (TAVR)] improves the outlook with acceptable procedural risk. Survivors of AVR enjoy life expectancy that is like that of age matched controls. AVR receives a class I indication from the American and European Guidelines, in the presence of symptoms attributable to AS or when left ventricular (LV) systolic dysfunction manifests. However, there are fallacies in timing the intervention based on symptoms or LV ejection fraction. If surgery is delayed till symptoms manifest or LV dysfunction occurs, surgical risks are increased, long term outcomes are poor and in half of the patients, LV function never normalizes. Because of these reasons, pre-emptive intervention based on non-conventional parameters is expected to save more lives and prevent LV dysfunction. Data are emerging towards this approach and researchers have started focussing their attention on biomarkers like brain natriuretic peptide, multimodality imaging like estimation of extracellular volume by cardiac magnetic resonance for choosing the appropriate time for intervention in asymptomatic individuals. A relatively inexpensive way of identifying such high-risk individuals is speckle tracking imaging and in the last decade sufficient data have accumulated in favour of this modality to identify patients who may be benefited by early intervention. Speckle tracking echocardiography is a well validated technique which enables highly reproducible, angle-independent assessment of regional and global LV systolic function in longitudinal, circumferential and radial planes. Longitudinal strain, which is predominantly governed by the subendocardial layer, is most sensitive in the presence of myocardial disease and well-studied. Moreover, when discrepancies occur between gradient and valve area leading to uncertainties about the severity of AS, strain imaging would be of value in predicting outcomes particularly in those with low flow low gradient AS with normal LV ejection fraction.
Keywords: Aortic stenosis, global longitudinal strain, left atrial strain, right ventricle strain
|How to cite this article:|
Somasundaram S, Ilayaraja U, Rajeswari K. Strain Imaging in Aortic Stenosis. J Indian Acad Echocardiogr Cardiovasc Imaging 2023;7:109-20
|How to cite this URL:|
Somasundaram S, Ilayaraja U, Rajeswari K. Strain Imaging in Aortic Stenosis. J Indian Acad Echocardiogr Cardiovasc Imaging [serial online] 2023 [cited 2023 Sep 27];7:109-20. Available from: https://jiaecho.org/text.asp?2023/7/2/109/384769
| Introduction|| |
Aortic stenosis (AS) of degenerative and bicuspid etiology and mitral regurgitation (MR) due to ischemic and degenerative causes are the most common valve diseases encountered in the developed countries. With an ever-increasing elderly population worldwide, degenerative AS is becoming the most common valve disease, affecting 3%–7% of the population. While the bicuspid aortic valve appears to be the most common cause in those below 65 years, degenerative (calcific) AS is the dominant cause in those >70 years. In the Euro Heart Study, AS contributed to 43.1% of all valve diseases. AS is a disease of aging as evident from the Norway Tromsø Study, which showed an age-related increase in the prevalence of AS-0.2% during 50-59 years, 1.3% during 60-69 years, 3.9% during 70-79 years, and 9.8% during 80-89 years. The incidence of AS was found to be 5/1000/year. Although rheumatic fever continues to be an important cause of valve diseases in developing countries, isolated aortic valve disease is rarely of rheumatic etiology. A retrospective study from a tertiary center in South India, based on echo laboratory data, indicated that isolated AS contributed to 7.3% of all valvular heart diseases, with degenerative calcification (65%) and bicuspid valve (33.9%) being the most common causes.
AS is a slowly progressive disease with decades of latency before symptoms develop. However, once the symptoms develop, the course is rapidly downhill. Contemporary data indicate that nearly half of the elderly individuals with symptomatic severe AS die within 1 year with an average life expectancy of 1.8 years. The prognosis is poor even among those who have asymptomatic severe AS; the median survival rates at 2, 4, and 8 years being 92%, 80%, and 65%, respectively, and aortic valve replacement (AVR)-free survival rates being 54%, 32%, and 12%, respectively. In another study of 114 patients with asymptomatic severe AS, the survival rate at 1, 2, and 3 years was 88%, 75%, and 63%, respectively. Recent data indicate that even those with moderate AS seem to have poor survival when compared to the general population. In the National Echocardiographic Database of Australia, 6.7% had mild AS, 1.4% moderate AS, and 2.6% severe AS. The 5-year mortality was 19% in those with any degree of AS, 56% in moderate AS, and 67% in severe AS. In a meta-analysis of 25 studies that enrolled patients with moderate AS, pooled rates per 100 person-years were 9 for all-cause death, 4.9 for cardiac death, 3.9 for heart failure, 1.1 for sudden death, and 7.2 for AVR. In those with moderate AS and reduced EF (<50%) or low stroke volume index (<35 ml/m2) or clinical heart failure, the prognosis is much worse with nearly 80% of them dying in 5 years.
Despite being a disease with poor outcomes, timely AVR [(surgical AVR (SAVR) or transcatheter AVR (TAVR)] improves the outlook with acceptable procedural risk. Survivors of AVR enjoy life expectancy that is similar to that of age-matched controls. AVR receives a class I indication from the American and European guidelines when patients are symptomatic or if they develop left ventricular (LV) systolic dysfunction. However, there are fallacies in timing the intervention based on symptoms, i.e., patients may subconsciously limit their activities, comorbid conditions like obesity or lung disease may be confounders, and sudden death or asymptomatic LV dysfunction may occur during the waiting period. Progressive fibrosis of the left ventricle which may occur during the medical follow-up may eventually be irreversible. Similarly, decisions based on LV ejection fraction (LVEF) may have their own disadvantages. Ejection fraction (EF) is a load-dependent parameter, and calculating EF in a hypertrophied, small-sized geometrically deformed ventricle may be fallacious. If surgery is delayed till LV dysfunction manifests, surgical risks are increased, long-term outcomes are poor, and in half of the patients, LV function never normalizes. Because of these reasons, preemptive intervention based on nonconventional parameters seems to be desirable. Data are emerging toward this approach, and researchers have started focusing their attention on biomarkers like brain natriuretic peptide (BNP) and multimodality imaging parameters like the estimation of extracellular volume by cardiac magnetic resonance (CMR) for choosing the appropriate time for intervention in asymptomatic individuals. A relatively inexpensive way of identifying such high-risk individuals is speckle-tracking imaging, and in the past decade, sufficient data have accumulated in favor of this modality to identify patients who may be benefited from early intervention. Speckle-tracking echocardiography (STE) is a well-validated technique in terms of high reproducibility and angle independency for assessing regional and global LV systolic function in the longitudinal, circumferential, and radial planes. Longitudinal strain (LS) imaging, which is essentially governed by the subendocardial layer, is a well-studied technique for the detection of early myocardial disease and is used in most of the studies for risk prediction. Moreover, global LS (GLS) is emerging as a novel technique for risk prediction improvement in certain subsets of patients with AS like low-flow low-gradient severe AS (LFLGAS) with normal EF and moderate AS. Apart from the preoperative selection of patients, strain imaging may be useful in predicting outcomes after AVR.
| Performing Strain Imaging in Aortic Stenosis|| |
Due to the established value of strain imaging, it should be routinely incorporated in the echocardiographic evaluation of all patients with moderate-to-severe AS. For LS measurements of LV, good-quality cine-loop recordings of apical two-chamber, three-chamber, and four-chamber views should be obtained and stored digitally for offline analysis. While acquiring apical images, the endocardium should be well-defined, and the entire LV should be included. The sector size should be adjusted in such a way as to include just the ventricles from the apex to AV valves without foreshortening. Sector width should be as minimum as possible to include the opposing walls. The frame rate should preferably be in the range between 40-80 per second. The offline analysis is done using a dedicated software. The operator marks three points in each of the three apical views; one at the apex and two on either side of the mitral valve. The software then automatically tracks the endocardial borders. The region of interest (ROI) or the endocardial borders should be manually adjusted to optimize tracking whenever required. Inadequately tracked segments may be excluded from the analysis. If more than two segments are not properly tracked, the strain values may be unreliable. The left ventricle is divided into six basal, six middle, and six apical segments (anteroseptal, anterior, lateral, inferolateral, inferior, and inferoseptal) constituting an 18-segment model. The strain and strain rate of each segment are analyzed individually. Apical LS (ALS), middle LS, and basal LS (BLS) may be individually calculated as the average of peak systolic LS of the six apical, middle, and basal segments, respectively. GLS is then calculated as the mean of the peak systolic LS of all 18 segments. Since myocardial contraction results in the shortening of longitudinal fibers, the GLS values are ideally expressed as negative values. However, for the sake of clarity, the GLS values are expressed in absolute values in recent publications, which are adopted in this article. Lower values indicate worse LV function and higher values indicate better LV function. Normal values differ from vendor to vendor, but are usually more than 18%. In a meta-analysis of different studies, GLS values ranged from 15.9% to 22.1%. A value of 15% or less is generally considered abnormal, and values of 16%–18% are considered borderline. BLS has been found to be a more sensitive marker of LV systolic dysfunction than GLS in some studies, and hence, the BLS/ALS ratio may also be calculated. With three-dimensional transthoracic echocardiography, it is possible to get automated measurements of the longitudinal, circumferential, and radial strain. The advantages of STE include the simplicity of the concept, the ease and rapidity with which it can be performed, and low intraobserver and interobserver variability (5%–8%). In contrast, the variability for EF estimation is around 8%–10%. Moreover, strain values are relatively less load and geometry dependent.
For left atrial (LA) strain, the nonforeshortened left atrium is imaged from apical four-chamber and apical two-chamber views. Although a biplane estimate is always preferable, a single-plane measurement from apical four-chamber is acceptable. After freezing the image in end-systole, the endocardium of left atrium is marked starting from one end of the annulus at the mitral leaflet-LA junction to the other end, excluding the orifices of the pulmonary veins and LA appendage. The software then automatically tracks the entire LA wall with the width of ROI being generally 3 mm. ROI should be manually adjusted to include the entire LA myocardium, including the right atrial side of the atrial septum but without including the pericardium. Due to the thin atrial wall, it is usually the LS that is measured in different phases of the cardiac cycle. For calculating the strain value, which is expressed as a percentage, either the onset of atrial contraction (defined by the onset of P-wave or ideally the onset of A-wave of mitral Doppler) or the end-diastole (defined as the nadir of the LA strain curve or the mitral closure in Doppler waveform) are used as reference points. ECG reference may be avoided particularly in bundle branch blocks. Values depend on the method adopted, and in general, end-diastole is chosen as the reference point, which can be done even in the absence of P-wave as in atrial fibrillation (AF). Formulae are available to calculate the value obtained by one method from the other method.
The following values are obtained from the strain curve that is obtained: (1) LA reservoir strain (LASr) = reservoir strain, measured as the difference of the strain value at the mitral valve opening minus that obtained at the ventricular end-diastole (positive value). (2) LA conduit strain (LAScd) = conduit strain, measured as the difference of the strain value at the onset of atrial contraction minus the value obtained at the mitral valve opening (negative value). In patients with AF, LAScd has the same value as LASr, but with a negative sign. (3) LASct = contraction phase strain, measured only in patients in sinus rhythm as the difference of the strain value at the ventricular end diastole minus the value at the onset of atrial contraction (negative value). The normal reference range for reservoir strain is 39% (38%–41%), conduit strain is 23% (21%–25%), and contractile strain is 17% (16–19%).
For measuring right ventricular (RV) strain, a right ventricle-focused view should be obtained in such a way that the apex is maximally visualized without foreshortening of right ventricle throughout the cardiac cycle. The RV endocardium is traced from the insertion point of the anterior tricuspid leaflet to that of the septal leaflet. The moderator band and papillary muscles are excluded while tracing the RV endocardium. The width of ROI should be ideally 5 mm. Manual adjustment is done to include from the endocardium to the epicardium without including the pericardium. The septum is included while tracing the endocardium; however, the septal values are ignored while calculating RV strain, as the RV free-wall strain is the one that is important. The normal RV free-wall strain is 28.5% ± 4.8%.
| Caveats|| |
Strain measurements are vendor specific, and hence, for comparison between the patients or for serial evaluation of the same subject, the same software should be used. In general, when there is mere LV hypertrophy (LVH) without dilatation, including the entire LV in a narrow sector is not difficult. However, when LV dysfunction supervenes and LV dilates, incorporating all the segments without a drop in the frame rate may not be always possible. One should remember that strain measurements in AS are likely to be influenced not only by the intrinsic contractility but also by the extent of hypertrophy (which may not always correlate with the severity of AS), associated coronary artery disease (CAD), and comorbid conditions such as diabetes and hypertension.
| Determinants of Global Longitudinal Strain in Aortic Stenosis|| |
Apart from the severity of obstruction, the degree of LVH, extent of fibrosis, LVEF, and additional vascular load imposed by hypertension and stiff aorta are the major determinants of GLS in AS [Figure 1]. In a study of 113 patients with AS, GLS was 17.1% ± 3.0% in mild AS, 16.4% ± 3.0% in moderate AS, and 14.5% ± 3.9% in severe AS. GLS showed a significant correlation with aortic valve area (AVA), mean pressure gradient, LVEF, LV mass index, and early diastolic mitral annular velocity (e'). In multiple step-wise regression analysis, the mean gradient, EF, and hypertension seemed to be independently associated with GLS. Comorbid conditions such as diabetes, hypertension [Figure 2], and obesity may cause an additional reduction of GLS in AS. Although associated CAD may affect the GLS value, studies have shown that GLS predicted high risk in patients with AS irrespective of the association with CAD.
|Figure 1: Global longitudinal strain of 9% in a patient with severe aortic stenosis, marked left ventricular hypertrophy, and ejection fraction of 41%|
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|Figure 2: Moderate aortic stenosis with left ventricular ejection fraction 65%, and no coronary artery disease. Global longitudinal strain was markedly reduced (5.4%), which could be because of associated uncontrolled severe hypertension|
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Associated uncontrolled severe hypertension may cause low GLS (vascular load).
| Global Longitudinal Strain as a Predictor of Symptoms|| |
GLS shows a rough correlation with the severity of AS, extent of LVH, LVEF, valvulo-arterial impedance, and functional capacity. However, it failed to show a correlation with the symptoms, as suggested by a study of 171 patients with AS. There was a significant overlap of the values among the four groups chosen in the study, namely, moderate AS with no symptoms, severe asymptomatic AS, severe symptomatic AS, and AS with low EF. The area under the curve of GLS was only 0.60 for diagnosing severe symptomatic AS in patients with normal EF. GLS was not independently associated with the presence of symptoms in the multivariate analysis performed after adjusting for age, gender, AVA, and LVEF. The lack of correlation between symptom status and GLS may be due to the following possibilities. In patients with severe AS with normal EF, diastolic dysfunction may be the primary cause of symptoms. Response to exercise and, hence, the symptoms depend on the myocardial response and also the valve reserve. A reduction in longitudinal performance may be compensated by increased radial and circumferential shortening thereby maintaining the stroke volume. Although there is a lack of correlation between GLS and symptoms, it serves as a robust indicator of clinical events, death, and need for AVR.
| Global Longitudinal Strain as a Measure of Subtle Left Ventricular Dysfunction|| |
As the severity of AS increases, a progressive increase in the LV systolic pressure tends to overcome the effects of obstruction and maintain forward flow. LVH that develops in response to increased afterload reduces LV wall stress. Such compensatory measures are responsible for the long asymptomatic phase of this disease. However, when the disease is advanced or longstanding, LV dysfunction starts occurring due to afterload mismatch or reduction of intrinsic contractility of the myocardium or both. LV dysfunction is at least partly reversible if caused by afterload mismatch, but may become irreversible when contractile dysfunction occurs. Detection of subtle or early LV dysfunction may allow the physician to recommend AVR at an appropriate time so that overt LV dysfunction can be prevented. Subendocardial muscle fibers are affected to a greater extent in many disease states, including AS, due to higher LV wall stress and relative reduction of perfusion in the subendocardium. Since subendocardial fibers are mostly vertically oriented, the assessment of longitudinal deformation by strain imaging would be useful in the detection of subtle (early) LV dysfunction. The obliquely oriented muscle fibers in the subepicardial layer and the circumferentially oriented muscle fibers in the middle myocardial layers determine the twist and circumferential mechanics, and hence, the EF. These fibers are less susceptible to damage from chronic pressure overload in AS. Studies have shown that LS is a better measure than LVEF in predicting outcomes in AS. Follow-up studies have identified a significant reduction of GLS values preceding a reduction in EF. In a study of 220 patients with asymptomatic severe AS, the mean GLS significantly deteriorated, from 18.0% ± 2.6% to 16.3% ± 2.8%, while EF remained unchanged during a 2-year follow-up. The cumulative event rates in terms of the onset of symptoms were significantly higher in those with a baseline LV GLS <18.2% compared with patients with an LV GLS of more than 18.2% (59% vs. 45% at 2-year follow-up and 91% vs. 79% at 5-year follow-up, respectively).
| Outcome Studies|| |
Due to its ability to detect subclinical LV dysfunction, GLS is expected to predict future clinical events better than EF. GLS emerged as a better predictor of all-cause mortality independent of AS severity and EF in a study of 688 patients. In that study, LV GLS was 18.2% ± 2.1%, 16.4% ± 2.3%, and 13.3% ± 3.7% in patients with mild, moderate, and severe AS, respectively. This finding of near-normal values in mild AS and progressive reduction of GLS with increasing severity of obstruction has been uniformly documented in many such studies. In those with severe AS and normal EF, a GLS value of >14% was associated with better survival than those with a value of <14%. Survival of patients with severe AS, normal EF, and a GLS value of <14% was indeed similar to those with reduced EF. Based on similar studies, recommending AVR seems to be justifiable when GLS is low. In another study of 146 patients with a mean valve area of 1.0 ± 0.4 cm2, the baseline GLS values were 22.1% ± 2% in controls, 18% ± 3% in mild AS, 17% ± 3% in moderate AS, and 15% ± 3% in severe AS. GLS showed a good correlation with LV mass index, LVEF, AS severity, and symptom class. During a median follow-up of 2.1 years, there were 20 deaths and 101 major adverse cardiac events (MACE). Unadjusted hazard ratios (HRs) for GLS (per %) were 1.42 for all-cause mortality and 1.09 for MACE. After adjusting for the clinical and echocardiographic variables, GLS remained a strong independent predictor of all-cause mortality with an HR of 1.38. It has been documented by Salaun et al. that LS showed a reduction not only in relation to the severity of AS but also the flow status. In this multicentric retrospective study, 582 patients with moderate-to-severe AS with preserved EF were included. Patients with severe AS were classified into four groups according to flow and gradient. The low flow was defined as a stroke volume index (SVI) <35 mL/m2 and a low gradient as the mean gradient <40 mm Hg. The LS values showed a graded reduction across the subgroups; 16.8% ± 5.2% in moderate AS, 16.1% ± 4.2% in normal-flow high-gradient severe AS (NFHGAS), 14.5% ± 4.2% in normal-flow low-gradient severe AS (NFLGAS), 13.8% ± 3.9% in low-flow high-gradient severe AS (LFHGAS), and 13.5% ± 4.2% in LFLGAS. The 2-year survival was 76.8% in LF/LG AS versus 89.3 in other groups. GLS of <13.5% predicted the overall mortality, both in severe as well as moderate AS. In a study of 395 AS patients (AVA <1.3 cm2, normal EF), in whom GLS was measured by velocity vector imaging, a value of <12.1% was independently associated with reduced survival. When added to the EuroSCORE and New York Heart Association (NYHA) functional status, there was a significant improvement in the prediction of mortality.
| Role of Global Longitudinal Strain in Asymptomatic Patients with Aortic Stenosis|| |
Nearly 40-50% of patients with severe AS may claim that they do not have symptoms attributable to AS - the so called asymptomatic AS. Symptoms may be truly absent or such patients might have limited their activities subconsciously, to avoid symptoms. Management of asymptomatic patients with severe AS continues to be a matter of debate. Watchful waiting, which is always hard to implement, may expose the patients to the risk of sudden death, progressive fibrosis of the left ventricle, or development of LV dysfunction. Aortic valve intervention in patients with EF <50% has been found to increase the risk of the procedure and result in suboptimal recovery of LV function with persistent symptoms, poor functional capacity and quality of life, and increased event rate. However, with a preemptive AVR, patients may have to face prosthetic valve-related issues like bleeding complications due to anticoagulant therapy in case of mechanical valves or valve failure necessitating a redo procedure in case of bioprosthetic valves. Conventional parameters like positive exercise testing, very high gradient, densely calcified valve, rapid progression of the disease, or elevation of BNP are being considered to identify individuals at risk for whom early surgery may be offered. Since the reduction of GLS signifies early or subtle LV dysfunction, it is emerging as a novel imaging parameter to identify those who would potentially benefit from early AVR.
A meta-analysis of 1067 patients with asymptomatic significant AS with LVEF >50% indicated that the GLS value of 14.7% served as a cutoff for identifying individuals who were at risk of dying. The HR for death was 2.62 for those with GLS lower than 14.7%. The relationship between GLS and mortality remained powerful even in those with an EF of >60%. In another meta-analysis of 1512 patients from nine studies, GLS not only predicted the mortality (HR: 1.42) but also the MACE, namely, myocardial infarction, ventricular arrhythmias, heart failure admissions or stroke (HR: 1.20), and the need for AVR (HR: 1.17). In a study of 332 patients with severe AS with no or mild symptoms, GLS of <15% obtained by vendor-independent two-dimensional (2D) strain software predicted a 2-fold increase in mortality during a median follow-up for 42 months. The GLS value of <15% improved the prediction of death rate when combined with AVA, SVI (<35 mL/m2), and EF (>60%).
| Global Longitudinal Strain in Low-flow Low-gradient Aortic Stenosis|| |
In nearly one-third of patients with significant AS, discrepancies may occur between the transvalvular gradient and estimated aortic valve area. Paradoxical LFLGAS, characterized by a mean gradient of <40 mm Hg and AVA of <1.0 cm2, is caused by a low SVI (< 35 mL/m2). In this subset of AS, decision-making regarding the timing of AVR is extremely difficult as it is debatable whether paradoxical LFLGAS carries a worse or similar prognosis when compared to normal-flow high-gradient AS (NFHGAS). The fact that GLS in paradoxical LFLGAS is much lower [Figure 3] than in NFHGAS has been highlighted by many studies. In the study performed by Lee, 16 out of 103 patients with severe AS had features of paradoxical LFLGAS. GLS was found to be much lower among them when compared to NFHGAS, (12.6% ± 4.4% versus 16.4% ± 4.0%). GLS showed a linear reduction with a reduction in SVI and an increase in mitral inflow E/ mitral annular e' ratio. Reduced GLS was associated with decreased functional capacity. Valvulo-arterial impedance was found to be a better predictor of GLS than the gradient in this study. Thus, GLS may be a novel predictor of events in the subset of patients with LFLGAS with normal EF.
|Figure 3: (a) Global longitudinal strain 14.5 in severe aortic stenosis (mean gradient 90 mm Hg). (b) Global longitudinal strain 15.5 in a patient with low-flow low-gradient aortic stenosis with a mean pressure gradient of 30 mm Hg|
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Even in those with classical LFLGAS (reduced EF), GLS has been found to be an incremental risk factor for mortality. Among those with LFLGAS with an EF of <40% enrolled in true- or pseudo-severe AS study, 3-year survival was 49% in those with a GLS value of <9%, while those with a GLS of >9% had a survival rate of 68%. In the multivariable analysis adjusted for age, CAD, projected AVA at a normal flow rate, and type of treatment (AVR versus conservative), GLS of <9% was independently associated with all-cause mortality with an HR of 2.18. A GLS value of <10% measured during dobutamine stress echocardiography was also independently associated with an increased risk of dying with an HR of 2.67.
| Improving Risk Prediction with Exercise Global Longitudinal Strain|| |
In asymptomatic patients with AS, exercise testing is generally recommended for risk prediction. Various parameters such as the occurrence of symptoms, blood pressure response, ECG changes, and increase in gradient have been found to predict events. The absolute values of GLS at peak exercise and the degree of change of GLS from rest to exercise may be novel methods of identifying those at risk. In a study of 207 patients with severe AS, a resting GLS of less than 15.5% and an exercise induced change of less than 1.4% from baseline, identified those in whom conventional parameters of abnormal exercise response could be elicited. A similar study looked at the baseline and postexercise strain values in predicting outcomes among 75 patients with moderate and severe AS. Clinical events occurred in 60% during a follow-up period of 34.5 ± 3.46 months. The rest GLS and BLS values of those in whom clinical events occurred versus those with no events were 14.7 ± 4.1 and 15.4 ± 4.2 versus 17.5 ± 3.31 and 17.8 ± 3.4. Peak exercise BLS of less than 17.99% appeared to be the best predictor of events. Failure of GLS to increase with exercise may prove to be a better risk predictor.
| Global Longitudinal Strain as A Risk Predictor in Moderate Aortic Stenosis|| |
Recent data suggest that prognosis is worse even in those with moderate AS, more so when EF is <50%. Even when EF is preserved, outcomes are poor in moderate AS, and GLS has been found to identify those at high risk in this subset. In a study of 287 patients with a median AVA of 1.25 cm2, the mortality was higher in those with a GLS value of <15.2% (HR 2.62). During a median follow-up of 3.9 years, the mortality was 21%, 35%, and 48% at 1, 3, and 5 years, respectively, in patients with GLS <15.2%, while it was 6%, 15%, and 19% in those with GLS >15.2%. It was true even in those with an EF of ≥60%. During follow-up, 106 (37%) patients underwent AVR. In those undergoing AVR, the prognosis was worse when GLS was <15.2%, with mortality rates of 2%, 10%, and 20% at 1, 3, and 5 years, respectively. The death rate was lower in those with a GLS of >15.2%, i.e., 2%, 5%, and 6% at 1, 3, and 5 years.
In a recent study of 760 patients with moderate AS (AVA 1.0–1.5 cm2) followed for a median period of 50 months, patients with either an LVEF of <50% or an LVEF of ≥50%, the mortality was higher if GLS was <16%. Survival at 1-, 3-, and 5-year follow-up was 82%, 71%, and 58% in the low-EF group and 92%, 77%, and 58% in the preserved EF group. In comparison, survival was better in those with LVEF ≥50% and LV GLS ≥16%, i.e., 96%, 91%, and 85%, respectively. The long-term outcomes were not different between patients with reduced EF and those with preserved EF when GLS was <16%. LV GLS identified higher risk even among those with LVEF of ≥60% or in those who were asymptomatic.
| Global Longitudinal Strain as An Outcome Predictor after Aortic Valve Replacement|| |
Preoperative GLS may also serve as a predictor of postoperative outcomes. Postoperative outcomes are adversely affected by myocardial fibrosis, and it is likely that GLS could be a marker of fibrosis and may serve as a better predictor of outcomes. In a study of 125 patients undergoing SAVR for severe AS, MACE, namely, cardiovascular death and heart failure hospitalizations, were numerically higher in those with decreased GLS. 5-year estimated MACE in the four groups with a GLS of − 20.0 ± 1.6, −16.9 ± 0.7, −14.3 ± 0.9, and − 10.3 ± 1.4 were 19%, 20%, 35%, and 49%, respectively. After correcting for the standard risk factors such as age, EF, LVH, and LA dilatation, GLS appeared to be the sole predictor of outcomes. In a similar study, the event rates were higher in patients with a decreased baseline LV GLS (<18.2%) compared with patients with normal LV GLS value (>18.2%) after 2 years (66% vs. 57%, respectively) and 5 years of follow-up (96% vs. 82%, respectively). In a study of 83 patients with severe AS, GLS was the strongest predictor of the lack of LV mass regression (LVMR). GLS value <9.9% predicted a lack of LVMR with 95% sensitivity and 87% specificity. Postoperative AF is a known complication of SAVR. In a study of 76 patients who had undergone SAVR, AF occurred in 15 (19.7%). In them, the preoperative LA global peak strain showed the highest diagnostic accuracy (HR 6.55) with a cutoff value of <16.9%. LA strain turned out to be a better predictor of AF than LA volume and E/e'.
Among 344 patients with AS and normal EF undergoing TAVR, the estimated actuarial 5-year survival was poor in those with a GLS of <16% when compared to those with a GLS of >16% (66.8% ± 7.5% vs. 81.7% ± 4.2%, HR: 2.26). The prognosis of those with reduced GLS and preserved EF was comparable to those with reduced EF. Survival free from cardiovascular death and heart failure rehospitalizations was also higher in the normal LV GLS group than in the impaired LV GLS group (82.1% ± 5.0% vs. 62.9% ± 8.7%). In a similar study of 75 symptomatic patients with severe LFLGAS with reduced EF undergoing TAVR, GLS was found to increase from 12.8% ± 3.2% to 16.3% at 6 months postprocedure. A GLS value of ≤12% identified those with a lack of significant flow reserve and a lack of reverse remodeling after TAVR. LV end-diastolic volume at the baseline and 6 months post-TAVR was 166.3 ± 10 mL and 147.8 ± 6.7 mL in those with a baseline GLS >16% and 176.3 ± 11.4 mL and 174.4 ± 9.8 mL in those with a GLS of <16%, respectively. Thus, the baseline GLS could predict an improvement in postprocedure EF and LV reverse remodeling after TAVR.
| Global Longitudinal Strain versus Basal Longitudinal Strain|| |
It has been shown in some studies that BLS (obtained by averaging the strain values of six basal segments) may be a better predictor of outcomes than GLS. In normal and in many diseases, including AS, LS values show a reduction from the apex to the base. In disease states, including AS, the basal strain may detect early LV dysfunction when compared to GLS. The apex contracts first allowing the increasing intracavitary pressure to exert its effect on the mid and basal myocardium. Moreover, based on Laplace's law, wall stress may be more at the base than at the apex due to larger cavity dimensions at the base. In a study of 171 patients classified into four different subsets, namely, nonsevere AS, asymptomatic severe AS with preserved EF, symptomatic severe AS with normal EF, and severe AS with low EF, BLS showed a better correlation with the symptom status than GLS. However, there was an overlap of values among these subgroups of AS. In patients with suboptimal windows, it is mostly possible to delineate the endocardium of the basal segments. Hence, if the 2D image quality of other segments is not good enough to get reliable global strain values, BLS may be used as an alternative.
| Circumferential and Radial Strain in Aortic Stenosis|| |
Myocardial function is heterogeneous in different layers of the myocardium. In contrast to LS, myocardial deformation in the radial and circumferential direction is more complex and poorly defined. In a study of 32 patients with AS and normal EF and 35 controls, in which the longitudinal, radial, and circumferential strain values were measured, there was no significant difference in circumferential strain in the subendocardial and subepicardial layers between the controls and the patients with AS. Similarly, there was no significant difference in the epicardial radial strain at the posterior and anteroseptal segments between the controls and the patients with AS. LS at both the posterior and anteroseptal segments was significantly decreased in the AS group compared with that in the control group. Moreover, endocardial radial strain values were significantly decreased in patients with AS, when compared to controls (anteroseptal: 18.2 ± 11.2 vs. 34.5 ± 14.8, P < 0.005; posterior: 25.2 ± 14.8 vs. 32.6 ± 12.6, P < 0.05). In the AS group, endocardial radial strain in the posterior and anteroseptal segments significantly correlated with the AVA.
In another study done by Bi et al., 2D and three-dimensional images were analyzed for GLS, global circumferential strain (GCS), global radial strain (GRS), basal rotation, apical rotation, and peak systolic twist in 168 patients with severe AS and EF ≥50%. The values were compared with the published normal ones. In patients with severe AS, GLS and GRS values were lower; however, GCS, apical rotation, and twist values were higher. GLS showed a correlation with valvulo-arterial impedance, a measure of LV afterload. The values from 2D measurement for patients with AS enrolled in this study versus normal values published already were 16.2 ± 2.1 versus 19.7% for GLS, 27.4 ± 4.6 versus 23.3% for GCS, 37.5 ± 8.2 versus 47.3% for GRS, −7.8° ± 2.2° versus − 7.5° ± 5.4° for basal rotation, 10.7° ± 4.0° versus 6.3° ± 3.5°, and 18.5° ± 4.7° versus 13.4° ± 8.2° for twist.
| Layer-specific Strain|| |
With the help of a dedicated software, it is possible to measure the subendocardial, subepicardial, and transmural strain values from the apical windows and similarly layer-specific circumferential strain from the short-axis window. In view of the increased susceptibility of vertically oriented subendocardial fibers in disease states, it is expected that the subendocardial layer LS may decrease earlier and to a greater degree than the subepicardial strain in AS. Fung et al. performed serial echocardiography in 86 patients with AS (19 mild, 15 moderate, and 52 severe), at the baseline and 12 months in 46 medically managed patients and after AVR in 40. Layer-specific longitudinal and circumferential strain measurements were done serially in AVR and medically managed patients. It was shown during follow-up that subendocardial strain showed reduction even in mild AS and was much worse in moderate and severe AS when compared to subepicardial or transmural strain. Similarly, it was the subendocardial strain that showed recovery earlier than the subepicardial strain after AVR. In another study of 211 patients with severe AS and EF >50% (97 asymptomatic), LS was measured in the subendocardial, midmyocardial, and epicardial layers. Although LVEF was similar, multilayer strain values were significantly lower in symptomatic AS patients, compared to asymptomatic AS and healthy controls (GLS: 17.9 ± 3.4 vs. 19.1 ± 3.1 vs. 20.7% ± 2.1%; endocardial LS: 20.1 ± 4.9 vs. 21.7 ± 4.2 vs. 23.4% ± 2.5%; and epicardial LS: 15.8 ± 3.1 vs. 16.8 ± 2.8 vs. 18.3% ± 1.8%). Endocardial LS was independently associated with symptoms and cardiovascular death. The best cutoff for the endocardial LS values was 20.6% (sensitivity 70% and specificity 52%). Endocardial LS (19.1 ± 3.3 vs. 20.7 ± 3.3), but not epicardial LS (15.2 ± 2.8 vs. 15.9 ± 2.5), also predicted the outcome in patients who were initially asymptomatic.
| Strain Imaging in Aortic Stenosis with Coronary Artery Disease|| |
Due to shared etiological factors and common atherosclerotic pathways, CAD commonly coexists with AS. CAD may coexist in more than 50% of those over 70 years and more than 65% in those over 80 years. Significant CAD is found in 30% of patients undergoing SAVR and in 45%–80% of patients undergoing TAVR. Multivessel CAD is common in TAVR recipients, seen in 50%, and the left main disease in 11%. Both AS and CAD are known to reduce GLS independently and more so in the combined disease. In Carstensen's study of 104 asymptomatic moderate-to-severe AS patients, 31% had coronary stenosis of >50% documented by computed tomography. GLS was reduced in patients with AS irrespective of the presence of CAD, but was much worse in those with AS and significant CAD (15.6% ± 2.5% in AS without CAD, 12.8% ± 2.3% in those with AS and significant CAD). Moreover, there may be an apex to the base gradient with lower values in the basal segments and higher values in the apical segments, in normal and in patients with isolated AS. It may get reversed in those with associated CAD with apical and midsegment strain being less than basal strain. It is probably because the distal segments suffer more from ischemia than the basal segments in epicardial coronary artery stenosis. The values for apical, mid, and basal strain in isolated AS and in those with combined AS and CAD were as follows: apical – 17.0% ± 4.5%, mid – 15.7% ± 2.7%, and basal – 14.2% ± 2.9% in those without CAD and apical – 10.9% ± 4.1%, mid – 13.3% ± 2.3%, and basal – 13.6% ± 2.8% in those with AS and CAD. Thus, a reversal of the base-to-apex gradient may suggest associated CAD.
| Strain Imaging in the Detection of Cardiac Amyloidosis in Aortic Stenosis|| |
Both degenerative AS and wild type of transthyretin (TTR) amyloidosis (ATTRwt) are diseases of aging, and it is no surprise that they coexist in the elderly population. Rarely, light chain type of amyloidosis (AAL) may occur with AS. 16% of ATTRwt patients have AS, and 4%–29% of patients with AS have ATTRwt. Nearly 30% of patients with paradoxical LFLGAS may have cardiac amyloidosis (CA)., Because patients with AS and CA do not favorably respond to AVR, and as treatment options are now available for CA, it is mandatory to exclude CA in the elderly with AS. There are a number of clinical and biochemical red flags which may raise suspicion of CA, and the echocardiographic findings may strengthen the suspicion. Anyhow, diagnosis is established only when there is confirmation by the histology of cardiac or other tissues or abnormal bone scintigraphy when AAL is excluded. LVH out of proportion to the severity of AS, ground-glass appearance of the myocardium, LV systolic dysfunction, thickened RV wall, atrial septum and valves, pericardial effusion, restrictive hemodynamics, and significant pulmonary hypertension with tricuspid regurgitation and RV dysfunction are some of the clues in 2D echocardiography. Although not very specific, apical sparing of the left ventricle in strain imaging (cherry on top appearance in bull's-eye plot and the ratio of average strain of the apical/mid and basal segments >2) may be a useful finding to consider CA. Also, the global strain may show a more significant reduction when AS coexists with CA.
In a study of 30 patients with AS and ATTRwt, 50 patients with AS without ATTRwt, and 31 patients with ATTRwt without AS, a GLS value of– 14% was found to be the best cutoff to diagnose ATTRwt CA among patients with AS, with a sensitivity and specificity of 90% and 58%, respectively. The best cutoff value of relative apical sparing (apical/mid and basal strain) to identify ATTRwt CA among patients with severe AS was 1.0, with a sensitivity and specificity of 89% and 68%, respectively. However, 35%, 25%, and 11% of patients who had ATTRwt without AS, with moderate AS, and with severe AS, respectively, did not reach this threshold. In contrast, 36% of patients with AS and no amyloidosis demonstrated apical sparing. LV GLS and LA strain rate were measured to establish the diagnostic utility of deformational imaging in another study of 72 patients with AS in whom bone scintigraphy was positive in 16. In those with a relative apical sparing index (RELAPS) of ≥1.0 and the peak LA longitudinal strain rate ≤0.47 s−1, 83.3% of patients showed 99mTc-pyrophosphate scintigraphy positivity. In those with RELAPS <1.0 and the peak LA longitudinal strain rate >0.47 s−1, bone scintigraphy was negative in 96.6%. In a recent study of 324 patients undergoing TAVR, a RELAPS of >1 was present in more than half of the patients with severe AS and only 1 out of 7 patients with a RELAPS >1.0 had positive scintigraphy. When the RELAPS was more than 1, the features of severe remodeling of LV were noted frequently. It may be concluded from these studies that RELAPS may not be a specific finding to detect CA in patients with AS, and the 2D features can, at best, suggest the possibility of CA. The septal apical-to-basal strain ratio of >2.1 and EF by strain ratio of >4.1 were also used as the markers of CA in studies but lacked specificity. Other imaging measures like CMR may be more specific than echocardiography.
| Left Atrial Strain as an Incremental Prognosticator|| |
Increased LA volume is a predictor of adverse events in AS. LV filling pressures are elevated in severe AS against which the left atrium has to function (passive conduit and active contraction phases) resulting in LA hypertension, LA enlargement, and LA fibrosis. Secondary mitral regurgitation that occurs in response to LV remodeling may further contribute to an increase in the LA size. Alteration of the LA wall strain values is expected to precede such structural (LA size) and gross functional changes (mitral and pulmonary vein Doppler) in the left atrium. LA strain is a surrogate of LA fibrosis and may also reflect LA mechanics, hemodynamics, and dysfunction. Since there is a close functional interplay between LA and LV, LA strain is expected to integrate changes in LV wall thickness, chamber size, systolic and diastolic function, and the additional effects of secondary mitral regurgitation that are commonly seen in severe AS.
In a study of 102 patients with severe AS and 80 patients with moderate AS with preserved EF without CAD, followed up for 40 months, LASr was lower for severe AS when compared to moderate AS (13.8% versus 23%). LASr showed a stronger correlation to AVA and mean gradient than LV GLS. Both LV GLS and LASr were significant predictors of clinical outcomes comprising heart failure, death, and AVR.
LASr, LAScd, and LASct were measured in another study of 173 patients with moderate-to-severe AS with normal EF and no or minimal symptoms. The authors looked at the rate of the primary outcome, which was a composite of all-cause death, heart failure admission, worsening of functional class to NYHA III or IV, acute coronary syndrome, or syncope. The secondary outcomes 1 and 2 comprised the same endpoints but excluded acute coronary syndrome and additionally included syncope, respectively. The median LASr, LAScd, and LASct were 27% (22%–32%), 12% (8%–15%), and 16% (13%–18%), respectively. Over a median of 2.7 years (1.4–4.6 years), the primary outcome and secondary outcomes 1 and 2 occurred in 38%, 36%, and 34% of patients, respectively. LASr <20%, LAScd <6%, and LASct <12% were identified as optimal cutoffs of the primary outcome. LA strain parameters were superior to the other key echocardiographic variables in predicting 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. LA strain values were superior to the hemodynamic variables and LV myocardial response, including LV GLS, and also independent of the usual clinical risk factors and natriuretic peptides, in predicting adverse outcomes. LASct <12% was associated with heart failure outcomes and LASr <20% with most of the worse clinical outcomes, again independent of BNP.
In a recent prospective study of 98 patients with congenital AS, LAScd was significantly lower when compared to controls (18.1% ± 8.7% vs. 23.5% ± 9.9%). Decreased LAScd (<21%) predicted cardiovascular events. The event-free survival was 6.7 years (6–7.3) in those with LAScd <21% compared with 7.8 (7.1-8.5) years in others. The authors proposed a three-stage impairment of LA function in AS: in stage 1, LA function is normal; in stage 2, LAScd decreases with or without an increase in LASct; and in stage 3, all the strain values decrease [Figure 4].
|Figure 4: (a) Left ventricular global longitudinal strain 17% in a patient with paradoxical low-flow low-gradient severe aortic stenosis, (b) Left atrial strain of the same patient, with reservoir strain 26%, conduit strain 19%, and contractile strain 6%. Lower left atrial strain values predict high risk even though left ventricular global longitudinal strain is normal|
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Lower LA strain values predict high risk even though LV GLS is near normal.
| Multichamber Strain|| |
Genereux proposed a novel staging for AS patients based on the extent of upstream involvement of chambers leading to extravalvular cardiac damage (CD). Stage 0, no extra-aortic valve CD; stage 1, LV damage evident from the presence of LVH (LV mass index >95 g/m2 in women and >115 g/m2 in men), elevated LV filling pressures (E/e' ratio >14), and/or mild LV systolic dysfunction (LVEF <60%); stage 2, LA and/or mitral valve damage as defined by the presence of LA enlargement (LA volume >34 ml/m2), AF, and/or ≥ moderate mitral regurgitation; stage 3, pulmonary vasculature and/or tricuspid valve damage as defined by the presence of pulmonary hypertension (systolic pulmonary arterial pressure ≥60 mmHg) ± moderate or greater tricuspid regurgitation; stage 4, RV damage as defined by the presence of ≥ moderate RV systolic dysfunction, identified by a multiparameter approach, including semiquantitative assessment by visual examination and quantitative assessment using the criteria of tricuspid annulus systolic velocity S' <9.5 cm/s and/or tricuspid annular plane systolic excursion (TAPSE) <17 mm. The extent of CD was independently associated with increased mortality after AVR in symptomatic patients with severe AS (HR: 1.46 per each increment in stage). This staging system was also found to predict mortality among asymptomatic patients with moderate-to-severe AS. Tastet had retrospectively analyzed 735 asymptomatic patients followed up for 2.6 years. There was a step-wise increase in mortality: 13% in stage 0; 25% in stage 1; 44% in stage 2, and 58% in stage 3–4. The HR for death adjusted for AVR was 1.32 per each increase in a stage. As an extension, Ye et al. included multichamber strain (MCS), i.e. LV, LA, and RV to assess the incremental benefit. The values of <15% for LV GLS, <24% for LA strain, and <25% for RV strain were considered to indicate impaired strain of the chamber concerned. 209 patients in the study had bicuspid AS (BAVAS) and 369 had tricuspid AS (TAVAS), with >90% having severe AS. MCS (per chamber increase) modestly correlated with CD staging (per stage increase). The 5-year survival was better for BAV-AS when compared to TAV-AS, 86.8% ± 2.4% versus 49.6 ± 2.7%. MCS provided an incremental prognostic value to CD staging in both BAV AS and TAV AS and improved risk classification of CD staging in TAV AS (continuous net reclassification index = 0.24). Despite similar AS severity, patients with BAV AS exhibited age-independent healthier strain values, which translated into age-independent lower MCS. Moreover, MCS offered a better prognostic value for both BAV AS and TAV AS, independent of CD staging. Patients who underwent AVR had a lower mortality rate than those who did not undergo AVR; however, the survival improvement afforded by AVR was attenuated in patients with impaired MCS.
| Global Longitudinal Strain for Reclassifying the Risk Based on Cardiac Damage|| |
Apart from being a sensitive tool to identify early chamber dysfunction, GLS may serve to reclassify the risk predicted by CD staging. As LV GLS can predict LV dysfunction before LVEF decreases, LA strain may decrease before enlargement or dysfunction of the left atrium develops, and similarly, RV free wall strain may detect RV dysfunction before TAPSE decreases, right ventricle dilates, or RVEF decreases. In a retrospective analysis of 616 patients with severe symptomatic AS enrolled in an ongoing registry, LV GLS was divided into 5 quintiles and assigned to different stages (LV GLS >18% for stage 0 CD, 15.8%–18% for stage 1 CD, 13.2–15.8% for stage 2 CD, 10–13.2% for stage 3 CD, and <10% for stage 4 CD). During the follow-up of 44 months, 89% required AVR and 38% died. Association of the stage of CD was mainly in stage 4 (HR: 2.33), while other stages of CD did not show a significant independent effect on prognosis. After incorporating GLS into the staging classification, stages 2–4 were independently associated with mortality, and with each increase in the stage of CD, all-cause mortality showed a progressive increase (stage 2: HR 4.35, stage 3: HR 4.82, and stage 4: HR 8.08). Incorporating GLS resulted in the reclassification of patients, with more patients entering into advanced stages 3–4. Based on conventional staging, 45% were in stage 2, 6% in stage 3, and 13% in stage 4. After incorporating GLS, 37% were in stage 2, 19% in stage 3, and 25% in stage 4. GLS was associated with all-cause mortality independent of the stage of CD and showed an incremental prognostic value over the clinical characteristics and stages of CD.
| Myocardial Work Indices in Aortic Stenosis|| |
An extended application of strain imaging is to derive myocardial work indices with the help of proprietary software. So far, LV systolic performance in AS is commonly evaluated by EF and GLS. These indices do not take into account the afterload (AS severity and peripheral vascular resistance) and, hence, may not reflect LV myocardial work (LVMW) or oxygen demand. Russell et al. described a novel method, wherein myocardial work could be estimated by incorporating blood pressure readings and strain data to derive a pressure–strain loop. With this technique, it is possible to measure the global work index (GWI), which is the total work of the left ventricle during a cardiac cycle; global constructive work (GCW), which represents the work that is functional to LV relaxation during diastole and contraction during systole; and global wasted work (GWW), which measures the amount of LV dyssynchrony or paradoxical myocardial lengthening or shortening that does not occur in the appropriate cardiac phase. From these parameters, LV global work efficiency (GWE), which is a global estimation of LV performance, is derived. In a study of 120 patients undergoing TAVR, LVMW indices were calculated. Patients in NYHA functional class III or IV had lower LV GLS, LV GWI, LV GCW, and RV free wall strain compared with those in class I or II. In contrast to LV GLS, LV GWI and LV GCW showed independent associations with NYHA functional class III or IV heart failure symptoms. The values obtained in those with class III-IV symptoms in comparison to those in class I-II were: GWI (mmHg%) 1427 ± 576 versus 1851 ± 723; GCW (mmHg%) 1776 ± 691 versus 2177 ± 851; GWW (mmHg%) 171 versus 152; and GWE (%) 89 versus 91. Changes in cardiac mechanics after TAVR in a group of 73 patients with severe AS were analyzed by De Rosa. The mean transvalvular gradient was significantly improved without significant changes in EF or GLS in the majority. The improvement in GWI and GCW that was seen after TAVR in the general study population was not evident among LFLGAS patients. Thus, the myocardial work indices might be useful to predict poor or nonresponders.
| Summary|| |
LV GLS derived using STE is a simple measure of contractile performance of longitudinal (subendocardial) fibers that can be easily and quickly obtained with less inter- and intraobserver variability. Artificial intelligence introduced in the software of recent echocardiographs has further simplified the process by obtaining auto measurements. GLS is an integrated measure of functional (contractility), hemodynamic (increased afterload caused by valve stenosis and compliance of aorta), and morphological changes (LVH and fibrosis) caused by AS. Routine incorporation of GLS in the evaluation of all patients with moderate-to-severe AS is justifiable, as it predicts exercise capacity, it correlates with the severity, magnitude of LVH, extent of fibrosis, and LVEF, and it predicts MACE and death rate both in symptomatic and asymptomatic patients. GLS is particularly useful in choosing candidates for early AVR, in those with paradoxical LFLGAS and patients with moderate AS. Strain parameters could also predict outcomes after SAVR and TAVR. Since the prognosis of patients with AS and EF <50% is comparable to those with normal EF and a low GLS (<16%), early AVR may be offered to them. Exercise GLS may have an incremental benefit in asymptomatic patients. MCS measurements add to the risk stratification measures of CD done with conventional echocardiography and help in the reclassification of patients, thereby improving risk prediction. Lower MCS values may be used to identify those asymptomatic patients with severe AS who would benefit from early AVR. Myocardial work indices are emerging as more robust indicators of cardiac mechanics in AS. Multimodality imaging, particularly CMR which can measure the expanded extracellular volume and estimation of biomarkers like BNP, may be included with strain measurements in the future to get a meaningful multiparametric assessment.
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