Strain Imaging in Aortic Regurgitation

Manivasagam Raja Gopal; M Bharathkumaran

doi:10.4103/jiae.jiae_21_23

REVIEW ARTICLE

Year : 2023 | Volume : 7 | Issue : 2 | Page : 121-127

Strain Imaging in Aortic Regurgitation

Manivasagam Raja Gopal, M Bharathkumaran
Department of Cardiology, Maruthi and TRP Hospitals, Tiruchirappalli, Tamil Nadu, India

Date of Submission	12-Apr-2023
Date of Acceptance	20-Jun-2023
Date of Web Publication	30-Aug-2023

Correspondence Address:
Manivasagam Raja Gopal
Department of Cardiology, Maruthi and TRP Hospitals, Tiruchirappalli, Tamil Nadu
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jiae.jiae_21_23

Abstract

Two-dimensional strain imaging has an established role in the detection of subtle or subclinical left ventricular (LV) dysfunction in cardiomyopathies. The application of strain imaging, particularly longitudinal strain (LS), is emerging as a simple yet powerful tool in the detection of the early decline of LV function in valvular heart diseases also, including aortic regurgitation (AR). The advantages of strain imaging include its simplicity of the concept and imaging technique, its rapidity, and less interpersonal variability. The detection of lower strain values may help the clinician to optimally time the surgical intervention among asymptomatic individuals with preserved ejection fraction (EF). Such a preemptive approach is expected to improve the surgical results and offer better outcomes in terms of longevity and reverse remodeling of LV. Numerous studies have confirmed that a global LS value of 19.5% is the ideal cutoff for the detection of early LV dysfunction in AR. It has been shown in studies that a decreased strain correlates with mortality in medically treated as well as in operated patients. Apart from being potentially helpful in the timing of surgery in asymptomatic individuals, the estimation of strain is also useful in the detection of the contractile reserve, which is translated into better postoperative outcomes. If this finding is supported by future studies, strain imaging may eventually replace stress echocardiography in evaluating asymptomatic patients with valve diseases. Even in patients with advanced disease and low EF, strain values are helpful in identifying the subset of individuals who show better response to surgery. A cutoff of 12% appears to be useful in the detection of responders in this high-risk group. The usefulness of radial and circumferential strain, apical and basal rotation, and layered strain remains to be established. The extension of strain measurements in assessing myocardial work appears to be an attractive option for assessing LV function without load dependency.

Keywords: Aortic regurgitation, prognosis, strain imaging

How to cite this article:
Gopal MR, Bharathkumaran M. Strain Imaging in Aortic Regurgitation. J Indian Acad Echocardiogr Cardiovasc Imaging 2023;7:121-7

How to cite this URL:
Gopal MR, Bharathkumaran M. Strain Imaging in Aortic Regurgitation. J Indian Acad Echocardiogr Cardiovasc Imaging [serial online] 2023 [cited 2023 Sep 27];7:121-7. Available from: https://jiaecho.org/text.asp?2023/7/2/121/384770

Introduction

Valvular heart diseases (VHDs) continue to impose a huge cardiovascular disease burden worldwide. Apart from being responsible for morbid events such as heart failure and arrhythmias (e.g., atrial fibrillation with systemic embolism), VHD is an important cause of cardiovascular deaths, particularly in the young and middle aged. National prevalence of VHD among US adults, corrected for age and sex distribution, was 2.5%, with a population frequency of aortic regurgitation (AR) of 0.5%.^[1] In that study group, the overall adjusted mortality risk ratio for VHD was 1.36–1.75. In Euro heart study,^[2] isolated AR occurred in 10.4% of the entire study group and 13.3% of those with isolated left-sided valve diseases. The degenerative disease was the cause of AR in 50.2%, rheumatic in 15.2%, congenital in 15.2%, and endocarditis in 7.5%. The prevalence of AR in the Framingham Heart study was 4.9%, with regurgitation of more than moderate severity occurring in 0.5%. While degenerative diseases constitute a major cause of VHD in the West, rheumatic heart disease (RHD) remains an important cause in India. AR seems to be a relatively common valve disease, but only next to mitral valve disease and aortic stenosis (AS). In a study of 13,289 patients with VHD, obtained from an echocardiographic laboratory database of a tertiary hospital in South India,^[3] isolated AR occurred in 5.8%. RHD and bicuspid aortic valve (BAV) were the most common causes. In addition, AR was commonly encountered in mixed valve diseases (MVDs), which occurred in 36.9% of the study population. The most common combination was mitral stenosis with AR and mitral regurgitation (MR) with AR, occurring in one-fourth of MVD each. Timely intervention for those with moderate-to-severe AR is expected to improve the symptoms and quality of life and reduce mortality. Watchful waiting for those with asymptomatic significant AR may result in clinically silent interstitial fibrosis and a decline in left ventricular (LV) systolic function, both of which may lead to increased surgical risk and suboptimal improvement of LV remodeling and performance. Attention is now focused on identifying subclinical LV dysfunction in such individuals using biomarkers and imaging parameters. Strain imaging is emerging as an important technique to detect subtle decline in LV function based on which early intervention may be advised for such individuals at risk of dying or developing LV dysfunction.

Etiology and Pathophysiology

AR may have either acute or chronic presentation. The former is almost always severe and caused by infective endocarditis, trauma, aortic dissection, or following balloon valvuloplasty or TAVR for AS. Emergency surgery is the only option for acute AR, without which rapidly worsening hemodynamics may prove fatal. The most common clinical presentation of AR is, however, chronic, caused by diseased valves or dilated aorta or both. Valvular causes include RHD, aortic sclerosis and calcification, infective endocarditis, congenital abnormalities of the valve (bicuspid or quadricuspid aortic valve, membranous subvalvular AS, and prolapse of cusp in ventricular septal defect), myxomatous degeneration, irradiation, drugs, and carcinoid. Vascular causes include hypertension, Marfan syndrome, annuloaortic ectasia, Ehlers–Danlos syndrome, ostegenesis imperfecta, aortic dissection or aneurysm, syphilis, and arteritis (giant cell arteritis, Takayasu arteritis, and Reiter syndrome). BAV with aortopathy and ankylosing spondylitis may result in AR due to combined aortic and valvular involvement.

In chronic AR, disease progression and clinical presentation are insidious, with progressive dilatation and hypertrophy of the left ventricle as compensatory measures to maintain forward stroke volume. In contrast to MR, which results in pure volume overload, AR results in combined volume and pressure overload. In chronic severe AR, LV volumes progressively increase, reaching very high values, as high as 250–300 mL, thereby qualifying the term “corbovinum.” Increased LV end-diastolic volume (LVEDV) is a compensatory measure to preserve forward stroke volume. Because of increased LV compliance of LV, LV end-diastolic pressures (LVEDP) are normal in the initial stages. LV mass increases because of eccentric hypertrophy and LV end-systolic stress may increase because of increased LV dimensions, both of which may lead to relative ischemia, particularly in the vulnerable subendocardium. In addition to increased LVEDV, increased systolic pressures due to larger stroke volume may be responsible for the elevated systolic overload. Subsequently, structural changes such as interstitial fibrosis may start occurring. All these maladaptive changes due to chronic volume and pressure overload may lead to decreased compliance of the left ventricle, increased LVEDP, and finally, decreased ejection fraction (EF). Decline in EF is initially due to afterload mismatch and subsequently due to a decrease in intrinsic contractility. Data obtained from earlier studies suggested a risk rate of 1%–2% per year for developing symptoms, LV dysfunction or mortality, among patients with moderate-to-severe AR and normal EF when LV end-systolic diameter (LVESD) was 40–49 mm. When LVESD exceeds 50 mm, the annual rate of development of symptoms, decline of EF, or need for surgery was 19% per year which rose to 25% if LVESD exceeded 55 mm. The annual rate of symptom onset was 25% if EF declined below 50%. In a contemporary study of 154 patients with moderate-to-severe AR, 77% required surgery or died in 10 years.^[4] The postoperative results in terms of lower mortality and improvement of LV volumes and EF are likely to be better if done before such irreversible structural changes occur.

Aortic valve replacement (AVR) is recommended for those with severe symptomatic AR irrespective of LV function and for asymptomatic patients with LVESD more than 50 mm (>25 mm/m² BSA) or LV end-diastolic dimension >65–70 mm or LVEF <50%. AVR is also indicated for patients with moderate-to-severe AR undergoing coronary artery bypass grafting or surgery for dilated ascending aorta or surgery for another significant valve disease.^[5] However, these cutoffs of LV dimensions and EF have been derived from studies done many years ago which had enrolled a small number of patients. It has been documented that surgical risk was higher and reverse remodeling of LV was suboptimal if surgery was delayed till such asymptomatic patients reached these values. Contemporary data indicate that the cutoffs for LV dimensions and EF, to recommend AVR need to be revised in asymptomatic patients with chronic severe AR. Risk of operated and medically followed up patients with severe AR and LVEF of <60%, LVESD of >20 mL/m², and LVESV of >45 mL/m², seems to be higher, although further studies are required to recommend such newer cutoffs for deciding AVR in asymptomatic patients.^[6],[7] Data from an international registry of BAV indicate that the mortality and the combined endpoint of death and need for AVR were higher when LVEF was below 60%.^[8] The hazard ratio (HR) for mortality was 1.83 when EF was between 50% and 59% and 1.97 when EF was 30%–49% compared to the group of patients with EF of 60%–70%. Since the options of valve repair and TAVR are available now in selected instances, more and more patients with asymptomatic severe AR are likely to be intervened much earlier than what the present guidelines suggest. Improved surgical skills and lower surgical risks in high-volume centers also suggest that surgery may be timed earlier. Since deformational imaging detects subclinical LV dysfunction well ahead of the decline in EF, researchers have started focussing on strain values to choose the optimal timing for intervention. Deformational imaging provides improved risk stratification even in those who undergo surgery after the onset of symptoms or reduction of LVEF.

Strain Imaging in Aortic Regurgitation – The Basic Concepts

Deformation imaging by echocardiography measures the degree of shortening and the speed of shortening of myocardial fibers, during any specific period, e.g., from end diastole to end systole. The extent of shortening or the ratio between the initial length and the final length is called strain, expressed as percentage. The velocity of shortening is measured as strain rate, which measures the rate at which the distance between two points changes with time and is expressed as s⁻¹. Because of less noise and angle independency, two-dimensional (2D) strain has virtually replaced Doppler strain in clinical practice. Moreover, in contrast to Doppler strain, 2D strain or speckle-tracking echocardiography (STE) can measure strain in longitudinal, circumferential, and radial directions. Because of the ease of measurement and the fact that the longitudinally oriented subendocardial fibers are affected earlier in disease states, longitudinal strain (LS) measurements have gained popularity. Moreover, longitudinal measurements are less noisy and less linked to LVEF when compared to circumferential and radial strain (RS). LS is measured in the six segments of myocardium visualized from each of the three apical views, namely apical long-axis, apical four-chamber, and apical two-chamber views. Global LS (GLS) is the average of these eighteen regional strain values and is the most widely used parameter to assess LV function. Since the distance between the two adjacent points in the longitudinal direction decreases in systole, the values are conventionally expressed in negative units. However, to avoid misinterpretation and for the ease of understanding the changes with a decline in LV function, many prefer to use absolute values which is also adopted in this article.

In contrast to myocardial diseases, there is a poor correlation between LVEF and LV strain values in VHD because the changes in wall thickness, ventricular dimensions, and geometry may also influence strain to a significant extent. If there is no change in EF, GLS may decrease with an increase in wall thickness and may increase with an increase in LV dimension. In contrast to AS, which is a pure pressure overload state and MR, which is a pure volume overload state, AR is a state of combined pressure and volume overload. The mean GLS values for asymptomatic moderate-to-severe valve disease are 16.2% for AS, 21.6% for MR, and 19.5% for AR.^[9]

Technical Considerations in Strain Measurements in Aortic Regurgitation

Since LV enlargement is very marked in severe AR, including the apical third of the LV segments in the image sector for LS imaging is generally difficult. Moreover, vigorous contraction of the left ventricle in AR may result in poor tracking of apical segments throughout the phases of the cardiac cycle. If the sector size is increased to accommodate all segments, the frame rate is likely to come down, which may affect strain values. A trade-off is often required to balance between the frame rate and sector size to get the best possible values. In an occasional patient in whom satisfactory images could not be obtained in the apical long-axis and two-chambers views, the apical four-chamber view-derived GLS alone seems to predict clinical events.

RS measurements do not face similar issues as one would be able to include the entire left ventricle in the short-axis imaging, but the commercial availability of software for RS is limited. Strain values are expected to be normal in mild AR. In moderate-to-severe AR with LV enlargement, the strain values are likely to be slightly higher than normal, because of dilated heart. With the progression of LV remodeling, strain values start decreasing and reduction of GLS precedes the decline of LVEF and onset of symptoms in majority of the circumstances.

Strain Imaging for Early Detection of Left Ventricular Dysfunction

Like in many other disease states, GLS values get reduced well ahead of decline of LVEF in AR also. Since the subendocardial longitudinal fibres get affected in disease processes including VHD, GLS values show a decrease before LVEF decreases. In addition, compensatory increase in epicardial RS and circumferential strain (CS) may also contribute to the preservation of EF in the early stages. Strain values are much less in those with reduced EF than in those with preserved EF. Even among those with normal EF, symptomatic individuals are likely to have lower strain values than asymptomatic individuals. In a study of 129 patients with moderate-to-severe AR and LVEF of >50%, GLS was lower in symptomatic individuals than in those without symptoms; 14.9% ± 3.0% versus 16.8% ± 2.5%.^[9] An example of a patient with chronic severe AR and normal EF with minimally decreased GLS value is shown in [Figure 1]. Normal or minimal decline of GLS implies a better outlook.

Figure 1: (a) Conventional 2D and doppler parameters indicative of chronic severe aortic regurgitation with normal ejection fraction. (b) Minimal decline of global longitudinal strain, implying favorable outlook. EF: Ejection fraction, GLS: Global longitudinal strain

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Among 49 asymptomatic individuals who were followed up, 26 developed an indication for AVR (either onset of symptoms or decline of EF to <50%). Impaired GLS predicted the need for surgery; 1% decrease in GLS was associated with an HR of 1.21 for developing an indication for surgery.^[9]

In a study of 67 patients,^[10] with severe AR and normal EF, GLS and strain rate were lower than controls 18.9% ± 2.4% versus 20.0% ±2.1%; 1.05% ± 0.19% versus 1.18 ± 0.15 1/s. GLS was normal and the strain rate was lower in the group of 27 patients with moderate AR. The primary endpoint of deterioration of EF to <50% occurred in 12 patients with severe AR and GLS of <18.5% predicted such decline in LVEF during follow-up.

In another study of 90 patients with AR (moderate in 31, severe with reduced EF in 17, and severe with preserved EF in 42), LS, RS (RS-total, inner half, and outer half) and CS (CS-inner, mid and outer layers) were calculated.^[11] In all patients, including those with moderate AR, LS was reduced. In those with severe AR with preserved EF, inner CS was significantly decreased when compared to controls (25.4% ± 4.2% vs. 27.8% ± 3.8%), while outer CS showed an increase (11.8% ± 2.3% vs. 10.6% ± 2.6%). Similarly, inner RS showed a gradual decrease with increasing severity of AR, while outer RS in severe AR with preserved EF was higher than in controls 52.5% ± 19.4% versus 37.9% ± 11.8%). Such a transmural compensation by epicardial layers is believed to compensate for the decline of deformation of subendocardial fibers resulting in the preservation of EF till late in the disease process. In the above-described study, CS and RS values of both inner and outer layers were decreased in those patients who had low EF. Somewhat similar results were obtained by Kaneko,^[12] who reported the layered strain pattern of 36 patients with chronic severe AR undergoing surgical correction. GRS of inner layer was much lower in patients with AR when compared to controls (28.9% ± 12.9% vs. 37.1% ± 9.1%), while GRS total and GRS of outer layer did not differ among these two groups. After AVR, inner layer GRS increased from 27.8% ± 12.5% to 37.7% ± 14.6%.

Global Longitudinal Strain as a Predictor of Disease Progression

In a group of 26 patients,^[13] aged 3–16 years with moderate-to-severe congenital AR without symptoms, followed for a period of 2.9 ± 1.2 years, a baseline GLS value of < 19.5% predicted disease progression (sensitivity 77.8%, specificity 94.1%) defined as development of symptoms, increase of LV volume >15% or decrease of EF by >10%. Average GLS was significantly less in patients with progressive AR compared to those with stable AR (17.8% ± 3.9% vs. 22.7% ± 2.7%. An example of a significant decline in GLS in a patient with chronic severe AR and normal EF is illustrated in [Figure 2].

Figure 2: (a) Conventional 2D and doppler findings suggestive of chronic severe aortic regurgitation with normal ejection fraction. (b) Significant decline in global longitudinal strain, implying poor prognosis. EF: Ejection fraction, GLS: Global longitudinal strain

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Strain Imaging as a Substitute for Exercise Study to Document Contractile Reserve

Exercise studies arbitrarily define that an increase of LVEF by >5% from baseline indicate the presence of contractile reserve and such patients are expected to do better and have optimal reverse remodeling after AVR. In a recently published study of 115 AR patients^[14] who underwent strain imaging and exercise studies, GLS of >12% identified those with contractile reserve with a sensitivity of 78% and a specificity of 84%.

Global Longitudinal Strain in Asymptomatic Aortic Regurgitation with Normal Ejection Fraction

In this “supposed to be” a low-risk group with AR, GLS appears to have incremental value in assessing mortality and is also helpful in reclassification of risk status. Natural history studies in the past have confirmed that death rates and heart failure hospitalizations are higher when symptoms occur or LVEF drops. Hence AVR, if done before the onset of such events is expected to yield better results in terms of lower surgical mortality and better recovery of LV remodeling. In one such study of 47 patients with asymptomatic AR referred for surgery based on LV dimensions,^[15] GLS was found to be lower when compared to values obtained in 31 controls (17.5% ± 3.1% vs. 22.1% ± 1.8%). However, global CS (21.7% ±3.4% vs. 22.6% ± 2.5%) and LVEF (59% ± 5% vs. 59% ± 6%) did not differ between the groups. GLS normalized to LVEDV (0.09 ± 0.04 vs. 0.23 ± 0.08) appeared to be a better discriminator in the study, at baseline and after surgery, in the detection of subtle LV dysfunction before surgery and recovery of myocardial function after surgery. It is worthy to note that while LVEF and absolute values of GLS showed a small reduction after surgery, GLS normalized to LVEDV demonstrated an increase, thereby demonstrating the influence of LV volume and geometry on GLS measurements. In a large series of 1063 patients with chronic severe AR with preserved EF and LVESD <25 mm/m², LV GLS obtained by velocity vector imaging predicted death in unoperated patients (37% of the study group). GLS of <19% was associated with a doubling of the risk of death during a follow-up period of 6.8 ± 3.0 years when compared to those with GLS of >19% (31% vs. 15%).^[16] In contrast, there was no difference in mortality in the operated group, whether GLS was more or <19%. There was an 11% increase in all-cause mortality for a 1% decrease in GLS. The clear message from this study is that when surgery is undertaken in those with normal EF before GLS decreases below 19%, the outlook would be good.

Global Longitudinal Strain as a Predictor of Death in Asymptomatic Aortic Regurgitation

In one of the largest series of patients with chronic severe AR, GLS proved to be the best predictor of death.^[17] Among 550 such patients followed for a median period of 4.8 years, 87 died (19 after AVR). Although LVEF and LVESV showed an association with mortality, GLS proved to be the best indicator. Death rate rose steeply with a reduction of GLS value below 15%. Those with GLS of <15% and LVESV index of >45 mL/m² had a four-fold increase in the death rate. In the study done by Park et al.,^[18] 60 patients with chronic severe AR were followed up for nearly 64 months, among whom 16 died during medical follow-up and 38 underwent AVR. Apical four-chamber-derived GLS was compared with other conventional clinical and 2D echo parameters for the predictive ability for mortality. GLS of <12% emerged as the strongest independent risk predictor of death both in medical as well operated groups with a HR of 1.313.

Global Longitudinal Strain as a Predictor of the need for Aortic Valve Replacement

Symptomatic status and LVEF <50% have been conventionally considered as class I indications for AVR in chronic severe AR. Decision based on resting LVEF has its own limitations. LVEF is load and heart rate dependent and the reproducibility of its measurements is limited. Irreversible changes tend to occur by that time EF starts decreasing below 50%. Recent studies imply that the EF cutoff for choosing asymptomatic patients for AVR need to be 60%, in order to intervene before such structural changes occur. The other way of minimizing LV damage and maximizing the reverse remodeling and improvement of EF after AVR is to exploit deformational imaging parameters which detect subtle LV systolic dysfunction. Kusunose et al. have shown in their study^[19] of 159 consecutive subjects with chronic asymptomatic moderate-to-severe AR with preserved EF (EF >50%), LVEDD <70 mm and LVESD <50 mm (<25 mm/m²) followed up for a period of 30 ± 21 months, 31% required surgery either because of symptoms or decline of EF <50% or both. Lower values of LV GLS were associated with the time to AVR; HR for one standard deviation difference of GLS was 1.62.

Global Longitudinal Strain as a Predictor of Outcomes after Aortic Valve Replacement

In a study of 52 patients with severe AR who underwent AVR, tissue doppler derived systolic RS rate of <1.82 per second predicted postoperative LV dysfunction with a sensitivity of 90.9% and a specificity of 73.2%.^[11] Speckle tracking derived strain parameters, namely systolic strain, systolic strain rate and diastolic strain rate were found to predict disease progression during conservative management in a group of 35 patients (−16.3% vs. −19.0%, −1.04 vs. −1.19 s⁻¹, and 1.20 vs. 1.60 s⁻¹, respectively). Similarly, these parameters obtained at baseline predicted worse outcome after AVR in the form of lack of improvement of symptoms or persistent LV dilatation in the group of 29 patients who were operated (−11.5% vs. −15.6%, −0.88 vs. −1.01 s⁻¹ and 0.98 vs. 1.33 s⁻¹ respectively).^[20]

GLS may show a decline after AVR which is attributed to decrease in LV volumes and hence the stretch. In contrast, GLS corrected to EDV namely, GLS/EDV ratio may show an increase after surgery. In general, a preoperative GLS value of <19% and postoperative decline of >5% from preoperative values are associated with increased mortality after AVR. In an observational study of 865 patients with chronic severe AR with minimal or no symptoms and LVEF of >50% who underwent AVR or repair, 12% died during a follow up period of 6.95 years. Mortality was higher in those with a preoperative GLS of <19% when compared to those with a GLS of >19% (15% vs. 10%). Moreover, postoperative GLS of >19% predicted better long-term survival (95% vs. 85%). A drop of GLS of >5% from baseline, in the postoperative period, was associated with worse survival.^[21]

In a surgical series of 98 patients, baseline GLS of > 18% predicted shorter duration of hospital stay, higher GLS values postoperatively and further improvement of GLS at 1 year follow up. In all patients, GLS showed a decline in the immediate postoperative period but improvement during follow up which was more significant in those with a baseline normal GLS.^[22]

Decision making is often difficult in the subgroup of patients with chronic severe AR manifesting severe LV dysfunction because of the high risk for surgery and unpredictability of recovery of LV function after surgery. In the study group of Li et al.,^[23] 38 patients with chronic severe AR with a very low EF (26.2% ± 5.3%) who showed an increment of EF of at least 8% with low dose dobutamine underwent AVR successfully. Though LV size and EF showed improvement in all patients, only 18 achieved better improvement of EF i. e. >40%. Baseline GLS of >7.8% and postdobutamine GLS of >9.4% predicted such better responders. Neither the baseline LVEDV nor LVESV could predict better response.

Value of Multidirectional Strain Imaging

Strain parameters in longitudinal, radial and circumferential directions can be obtained by 3D STE which may be helpful in assessing disease progression. 3D strain imaging is less time consuming and less operator dependent which are the advantages over 2D strain analysis. It also provides insight into alterations of cardiac mechanics with varying severity of AR and during progression of disease in follow up. 3D strain imaging was performed in a study of 135 patients^[24] with AR (48 mild, 40 moderate and 47 severe). During follow up of medically treated patients and operated subjects for a period of 2.1 ± 0.37 years, there was reduction of GLS in both moderate and severe AR patients when compared to controls (control 22.08% ± 2.13%, moderate AR 18.8% ± 2.68%, severe AR 16.06% ±3.65%). GCS showed no change across the groups. GRS was similar to controls in moderate AR but reduced in severe AR (control 39.92% ± 5.43%, moderate AR 39.56% ± 4.75%, severe AR 34.40% ± 5.15%). Basal rotation did not change across the groups, but apical rotation and twist showed an increase in moderate AR, but reduced in severe AR. Thus, a progressive decline of GLS, GRS and twist may indicate disease progression and allow us to optimally time AVR.

Estimation of Left Ventricular Myocardial Work in Aortic Regurgitation

Though GLS has emerged as a robust parameter for early detection of LV dysfunction, it is afterload dependent. Myocardial work parameters are calculated by a proprietary software based on strain values and brachial cuff blood pressure (surrogate of LV systolic pressure, a measure of afterload). An LV pressure strain curve is then constructed from LV GLS data of the entire cardiac cycle. Cardiac work is calculated as a function of time throughout the cardiac cycle and four parameters are derived: (1) LV global work index (GWI, mm Hg%), defined as total work within the area of the LV pressure-strain loop, calculated from mitral valve closure to opening; (2) LV global constructive work (GCW, mm Hg%), defined as work performed during shortening in systole or during lengthening in isovolumic relaxation; (3) LV global wasted work (GWW, mm Hg%), defined as work performed during lengthening in systole or during shortening against a closed aortic valve in isovolumic relaxation; and (4) LV global work efficiency (GWE, %), calculated as LV GCW divided by the sum of LV GCW and LV GWW and expressed as a percentage. Meucci et al.^[25] studied 57 patients with moderate-to-severe AR and normal EF who underwent AVR. When compared to published normal reference values, GWI was preserved in 82% and increased in 18%. GCW was normal in 74% and increased in 25%. GWE was preserved in all. LV GWI, GCW and GWE decreased after AVR without a change in GWW. Postoperative impairment of LV GWI was observed in 28% and was closely related to reduced LV reverse remodelling. Thus myocardial work may emerge as a powerful load independent tool to assess myocardial mechanics in AR and has the potential to guide optimal timing of AVR in asymptomatic severe AR.

Conclusion

Current medical literature has abundant data confirming the value of strain imaging in detection of subtle LV dysfunction in patients with chronic significant AR. Measuring strain parameters is most useful in asymptomatic patients with moderate to severe AR with preserved LVEF. LS is the most commonly measured parameter because of technical reasons like simplicity and reproducibility of measurement and physiological reasons i.e., subendocardium with mostly vertically oriented fibres is more vulnerable in disease conditions. A GLS value of <19% may identify those individuals who are at high risk of dying, developing symptoms or requiring surgery. Instead of waiting for the symptoms to occur or LV dysfunction to manifest, timing of surgery when GLS gets lowered below 19% may be more appropriate. Disease progression is also faster when pre-operative GLS is below 19%. Moreover, surgical outcomes and long-term outlook are better and LV reverse remodeling is more complete when GLS is >19%. On the contrary, a drop GLS >5% after AVR predict worse outcomes. GLS of >12% predicts contractile reserve after exercise and hence better clinical outlook. Even in those with reduced EF, a baseline of GLS >7.8% and post dobutamine GLS of 9.4% predicted better recovery of LV function after surgery. GLS normalized to EDV, multidirectional strain measurements, myocardial work estimation may prove to be better predictors than GLS if supported by more studies. Multimodality and multiparametric model combining 2D derived LV volumes and EF, STE derived strain parameters, cardiac magnetic resonance derived extracellular volume and replacement fibrosis and biomarker elevation (natriuretic peptides, troponin) may be more accurate in detecting early disease decompensation and could be the future in the management of patients with AR.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. Burden of valvular heart diseases: A population-based study. Lancet 2006;368:1005-11.
2.	Iung B, Baron G, Butchart EG, Delahaye F, Gohlke-Bärwolf C, Levang OW, et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on valvular heart disease. Eur Heart J 2003;24:1231-43.
3.	Manjunath CN, Srinivas P, Ravindranath KS, Dhanalakshmi C. Incidence and patterns of valvular heart disease in a tertiary care high-volume cardiac center: A single center experience. Indian Heart J 2014;66:320-6.
4.	Lamba M, Bridgman P. Contemporary natural history of patients with severe and moderate to severe aortic regurgitation. Heart Lung Circ 2017;26:S1.
5.	Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, et al. 2021 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J 2022;43:561-632.
6.	Yang LT, Michelena HI, Scott CG, Enriquez-Sarano M, Pislaru SV, Schaff HV, et al. Outcomes in chronic hemodynamically significant aortic regurgitation and limitations of current guidelines. J Am Coll Cardiol 2019;73:1741-52.
7.	Yang LT, Anand V, Zambito EI, Pellikka PA, Scott CG, Thapa P, et al. Association of echocardiographic left ventricular end-systolic volume and volume-derived ejection fraction with outcome in asymptomatic chronic aortic regurgitation. JAMA Cardiol 2021;6:189-98.
8.	Hecht S, Butcher SC, Pio SM, Kong WK, Singh GK, Ng AC, et al. Impact of left ventricular ejection fraction on clinical outcomes in bicuspid aortic valve disease. J Am Coll Cardiol 2022;80:1071-84.
9.	Ewe SH, Haeck ML, Ng AC, Witkowski TG, Auger D, Leong DP, et al. Detection of subtle left ventricular systolic dysfunction in patients with significant aortic regurgitation and preserved left ventricular ejection fraction: Speckle tracking echocardiographic analysis. Eur Heart J Cardiovasc Imaging 2015;16:992-9.
10.	Verseckaite R, Mizariene V, Montvilaite A, Auguste I, Bieseviciene M, Laukaitiene J, et al. The predictive value of left ventricular myocardium mechanics evaluation in asymptomatic patients with aortic regurgitation and preserved left ventricular ejection fraction. A long-term speckle-tracking echocardiographic study. Echocardiography 2018;35:1277-88.
11.	Iida N, Seo Y, Ishizu T, Nakajima H, Atsumi A, Yamamoto M, et al. Transmural compensation of myocardial deformation to preserve left ventricular ejection performance in chronic aortic regurgitation. J Am Soc Echocardiogr 2012;25:620-8.
12.	Kaneko A, Tanaka H, Onishi T, Ryo K, Matsumoto K, Okita Y, et al. Subendocardial dysfunction in patients with chronic severe aortic regurgitation and preserved ejection fraction detected with speckle-tracking strain imaging and transmural myocardial strain profile. Eur Heart J Cardiovasc Imaging 2013;14:339-46.
13.	Di Salvo G, Rea A, Mormile A, Limongelli G, D'Andrea A, Pergola V, et al. Usefulness of bidimensional strain imaging for predicting outcome in asymptomatic patients aged≤16 years with isolated moderate to severe aortic regurgitation. Am J Cardiol 2012;110:1051-5.
14.	D'Andrea A, Sperlongano S, Formisano T, Tocci G, Cameli M, Tusa M, et al. Stress echocardiography and strain in aortic regurgitation (SESAR protocol): Left ventricular contractile reserve and myocardial work in asymptomatic patients with severe aortic regurgitation. Echocardiography 2020;37:1213-21.
15.	Smedsrud MK, Pettersen E, Gjesdal O, Svennevig JL, Andersen K, Ihlen H, et al. Detection of left ventricular dysfunction by global longitudinal systolic strain in patients with chronic aortic regurgitation. J Am Soc Echocardiogr 2011;24:1253-9.
16.	Alashi A, Mentias A, Abdallah A, Feng K, Gillinov AM, Rodriguez LL, et al. Incremental prognostic utility of left ventricular global longitudinal strain in asymptomatic patients with significant chronic aortic regurgitation and preserved left ventricular ejection fraction. JACC Cardiovasc Imaging 2018;11:673-82.
17.	Yang LT, Takeuchi M, Scott CG, Thapa P, Wang TD, Villarraga HR, et al. Automated global longitudinal strain exhibits a robust association with death in asymptomatic chronic aortic regurgitation. J Am Soc Echocardiogr 2022;35:692-702.e8.
18.	Park SH, Yang YA, Kim KY, Park SM, Kim HN, Kim JH, et al. Left ventricular strain as predictor of chronic aortic regurgitation. J Cardiovasc Ultrasound 2015;23:78-85.
19.	Kusunose K, Agarwal S, Marwick TH, Griffin BP, Popović ZB. Decision making in asymptomatic aortic regurgitation in the era of guidelines: Incremental values of resting and exercise cardiac dysfunction. Circ Cardiovasc Imaging 2014;7:352-62.
20.	Olsen NT, Sogaard P, Larsson HB, Goetze JP, Jons C, Mogelvang R, et al. Speckle-tracking echocardiography for predicting outcome in chronic aortic regurgitation during conservative management and after surgery. JACC Cardiovasc Imaging 2011;4:223-30.
21.	Alashi A, Khullar T, Mentias A, Gillinov AM, Roselli EE, Svensson LG, et al. Long-term outcomes after aortic valve surgery in patients with asymptomatic chronic aortic regurgitation and preserved LVEF: Impact of baseline and follow-up global longitudinal strain. JACC Cardiovasc Imaging 2020;13:12-21.
22.	Hua X, Fuhrmann R, Sinning C, Holst T, Pecha S, Al Assar Y, et al. Assessment of cardiac performance by global longitudinal strain after aortic valve surgery in severe aortic regurgitation. Thorac Cardiovasc Surg 2023;71(S 01):S1-S72.
23.	Li Q, Zuo W, Liu Y, Chen B, Wu Y, Dong L, et al. Value of speckle tracking echocardiography combined with stress echocardiography in predicting surgical outcome of severe aortic regurgitation with markedly reduced left ventricular function. Rev Cardiovasc Med 2023;24:114.
24.	Zeng Q, Wang S, Zhang L, Li Y, Cheng L, Wang J, et al. Left ventricular remodeling and its progression in asymptomatic patients with chronic aortic regurgitation: Evaluation by speckle-tracking echocardiography. J Am Soc Echocardiogr 2021;34:360-9.
25.	Meucci MC, Butcher SC, Galloo X, van der Velde ET, Marsan NA, Bax JJ, et al. Noninvasive left ventricular myocardial work in patients with chronic aortic regurgitation and preserved left ventricular ejection fraction. J Am Soc Echocardiogr 2022;35:703-11.e3.