Myocardial Work in Aortic Regurgitation: It Also Works!

The management of chronic severe aortic regurgitation (AR), specifically the timing of intervention, remains challenging. The interplay between increasing left ventricular (LV) dilation and eccentric LV hypertrophy maintains stroke volume, resulting in both an increased preload and an increased afterload state. These mechanisms account for the “long latent phase” of chronic severe AR. Only once these mechanisms of LV compensation are exhausted does LV ejection fraction (LVEF) begin to decline. The 2020 American College of Cardiology/American Heart Association valve guidelines are similar to European guidelines and recommend intervention for chronic severe AR (1) in symptomatic patients, (2) in asymptomatic patients undergoing concomitant cardiac surgery, or (3) in asymptomatic patients with echocardiographic signs of LV systolic dysfunction (LVEF < 55%) or severe LV dilation, defined by two-dimensional echocardiographic measurements of LV end-systolic diameter >50 mm or indexed LV end-systolic diameter >25 mm/m2.1Otto C.M. Nishimura R.A. Bonow R.O. Carabello B.A. Erwin 3rd, J.P. Gentile F. et al.2020 ACC/AHA guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.Circulation. 2021; 143: e35-e71PubMed Google Scholar Yet, even when following a guidelines-based strategy, there is a high incidence of persistent LV dysfunction and cardiovascular morbidity post–aortic valve replacement (AVR). Hence, while the symptom-based waiting strategy will fix the AR, it may not fix the myocardial dysfunction. Our current algorithm for timing of AR surgery does not fully capture all patients at risk for suboptimal postoperative outcomes. What do we know about myocardial dysfunction in chronic severe AR before LVEF declines? Studies utilizing both magnetic resonance imaging (MRI) and echocardiographic imaging modalities have demonstrated that subclinical myocardial dysfunction often precedes development of symptoms. Cardiac MRI has been used in chronic AR to quantify regurgitation and evaluate for subclinical LV dysfunction, not only by LV volumes but also by markers for fibrosis such as presence of delayed gadolinium enhancement and/or increased extracellular volume >25%.2Senapati A. Malahfji M. Debs D. Yang E.Y. Nguyen D.T. Graviss E.A. et al.Regional replacement and diffuse interstitial fibrosis in aortic regurgitation: prognostic implications from cardiac magnetic resonance.JACC Cardiovasc Imaging. 2021; 14: 2170-2182Crossref PubMed Scopus (7) Google Scholar In echocardiography, peak global longitudinal strain (GLS) has also been shown to be a marker of clinical outcomes in chronic AR patients.3Alashi A. Mentias A. Abdallah A. Feng K. Gillinov A.M. Rodriguez L.L. 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: 673-682Crossref PubMed Scopus (62) Google Scholar,4Alashi A. Khullar T. Mentias A. Gillinov A.M. Roselli E.E. Svensson L.G. 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: 12-21Crossref PubMed Scopus (41) Google Scholar Abnormal preoperative peak GLS (worse than –19%) and an absolute worsening of 5% of GLS postoperatively were associated with increased mortality following AVR. Global longitudinal strain is affected by afterload, and a high afterload state (such as chronic AR) may mask the true LV contractility. Thus, GLS offers some insight into subclinical LV dysfunction, but GLS values alone cannot predict optimal timing of intervention since this parameter does not incorporate LV loading conditions. Myocardial work is a novel tool for assessing myocardial function by echocardiography, which overcomes the afterload limitations of GLS analysis.5Roemer S. Jaglan A. Santos D. Umland M. Jain R. Tajik A.J. et al.The utility of myocardial work in clinical practice.J Am Soc Echocardiogr. 2021; 34: 807-818Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar Peak GLS is calculated using the three standard transthoracic apical views at a frame rate >40 frames/sec. Afterload is estimated using noninvasive brachial cuff pressure, a surrogate for LV systolic pressure. Myocardial work indices are then calculated from GLS and blood pressure measurements using proprietary software (GE Healthcare Systems, Pewaukee, WI). The resultant “pressure-strain” graph is similar to the “pressure-volume” loop created in the cardiac catheterization laboratory. The area within this curve represents LV stroke work. Myocardial work has been demonstrated to have value in cardiomyopathies, hypertension, and LV dysynchrony. It has also been shown to have value in valvular disease, particularly in aortic stenosis,6Jain R. Bajwa T. Roemer S. Huisheree H. Allaqaband S.Q. Kroboth S. et al.Myocardial work assessment in severe aortic stenosis undergoing transcatheter aortic valve replacement.Eur Heart J Cardiovasc Imaging. 2021; 22: 715-721Crossref PubMed Scopus (12) Google Scholar,7Fortuni F. Butcher S.C. van der Kley F. Lustosa R.P. Karalis I. de Weger A. et al.Left ventricular myocardial work in patients with severe aortic stenosis.J Am Soc Echocardiogr. 2021; 34: 257-266Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar an increased afterload state. The current paper published in the Journal of the American Society of Echocardiography, “Noninvasive Left Ventricular Myocardial Work in Patients with Chronic Aortic Regurgitation and Preserved Left Ventricular Ejection Fraction” by Meucci et al.,8Meucci M.C. Butcher S.C. Galloo X. van der Velde E.T. Marsan N.A. Bax J.J. 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: 703-711Abstract Full Text Full Text PDF Scopus (1) Google Scholar expands upon our knowledge of myocardial work in valvular disease and is the first publication evaluating myocardial work in AR. In this pioneering study, 57 patients with chronic AR who underwent surgical AVR were evaluated by echocardiography pre- and postoperatively. These were “pure” AR patients, as those with mixed valve disease, endocarditis, aorta pathology, or multiple valvular pathologies were excluded. As expected, the baseline values of LVEF were normal by study design (mean LVEF, 59.7 ± 4.4) with normal (83%) or increased (17%) global work index (GWI). The mean absolute GLS was 18.4% ± 3% and was normal in 68% of patients (using gender-based cutoffs, <16.7% in men and <17.8% in women). In chronic severe AR, the myocardium remained efficient (as defined by global work efficiency) and productive (as defined by global constructive work) without significant wasted work (as defined by global wasted work). Absolute GLS and GWI had good correlation, with differences driven primarily by hypertensive patients. Myocardial work indices correlated moderately with AR severity but not with total LV volumes or LV mass index. Post-AVR, LVEF did not change significantly, but absolute GLS worsened (preop 18.4 ± 3.0 vs postop 15.2 ± 2.8; P < .0001). The postoperative impairment of GLS (72% patients had abnormal GLS) is consistent with prior studies post-AVR in AR patients. Mean myocardial work (GWI), constructive work (i.e., global constructive work), and myocardial efficiency (i.e., global work efficiency) all became abnormal post-AVR but not to the same extent as GLS. Even in the presence of significant GLS impairment (72%), there was less impairment of GWI (28% of patients). This mismatch in GLS and GWI impairment could be driven by lower blood pressure post-AVR versus decreased myocardial contractility. In comparing groups with preserved GWI versus impaired GWI postoperatively, notable differences included more hypertension, higher LVEF, and higher absolute GLS value in the preserved GWI group. To further clarify the interaction of GLS and blood pressure with post-AVR myocardial work indices, the authors separated the post-AVR population into three groups (group I, preserved GWI and GLS; group II, impaired GLS, preserved GWI; group III, impaired GLS and GWI). The authors found that hypertension post-AVR is an important driver, but more reverse LV remodeling (defined as lower LV end-diastolic volume) was seen in those with preserved compared with those with impaired LV myocardial work. This deepens our understanding of hypertension and reverse LV remodeling post-AVR. This study is not without limitations. Myocardial work analysis requires optimal image quality (15 patients were excluded due to poor image quality) and a reliable noninvasive cuff pressure at the time of echocardiography (31 patients were excluded due to missing blood pressure). As the authors have rightly noted, it is difficult to compare patients from 2002 to present-day patients given improvements in bypass time, surgical techniques, and myocardial protective measures during this 17-year period. There was also significant heterogeneity in the type of AVR (repair, mechanical, biologic), and case numbers were too low in each subgroup to detect any clinical differences in myocardial recovery. In addition, both moderate and severe AR patients were included in this study; thus, it is unclear how to compare this study to studies of severe AR alone. What were the baseline gradients of surgical AVR? Were they clinically significant? Because if they were, they could affect myocardial work analysis since a pressure gradient at the aortic valve level would mean that the peripheral blood pressure is not a reliable direct measure of the LV pressure. These questions remain to be answered. Finally, preliminary work on the effects of transcatheter AVR on myocardial function in chronic AR is ongoing. Expanded experience and future myocardial work research will, no doubt, overcome these limitations. As an example of clinical application of myocardial work in AR, we present a case in Figure 1. This 19-year-old man presented for an echocardiogram for collegiate sports screening. He was found to have a bicuspid aortic valve (fusion of right coronary and left coronary cusp with small raphe), prolapsing leaflets, and severe asymptomatic chronic regurgitation—regurgitant volume = 96 mL and effective regurgitant orifice area (proximal isovelocity surface area method) = 0.3 cm2. He had significant LV dilation, with extreme LV end-diastolic volume index and LV end-systolic dimension indexed to body surface area. He had no evidence of aortopathy or coarctation. Myocardial work was mildly reduced despite preserved LVEF (54%) and preserved GLS (–19%) in the setting of normal systolic blood pressure. Cardiac MRI demonstrated subclinical myocardial dysfunction, increased extracellular volume index, and delayed gadolinium enhancement. Three months after AVR, another echocardiogram was performed. Postoperatively, LV volumes decreased significantly. While LVEF was preserved (LVEF = 54%), both GLS and myocardial work were significantly impaired. According to the guidelines, we operated on this patient in a timely fashion. Yet myocardial recovery was not seen even with the reductions in myocardial volumes. We look forward to more generalized experience and larger studies to better define preoperatively the specific groups of severe chronic AR patients who will have normal myocardial mechanics postoperatively. In conclusion, Meucci et al.8Meucci M.C. Butcher S.C. Galloo X. van der Velde E.T. Marsan N.A. Bax J.J. 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: 703-711Abstract Full Text Full Text PDF Scopus (1) Google Scholar should be commended for this hypothesis-generating manuscript, and larger studies will deepen our understanding of myocardial work in chronic AR. Historically, asymptomatic chronic severe AR is clinically well compensated, and patients become symptomatic at the extreme end. In decades past, the criteria for operation in asymptomatic chronic severe AR were as high as an LV end-diastolic diameter of 75 mm. We have learned now that the symptom-based strategy can be misleading and the use of LV size thresholds may not fully capture subclinical LV dysfunction. Myocardial work is a novel and load-independent parameter of LV myocardial mechanics, which has the potential to provide guidance on optimal timing for intervention in AR to prevent postoperative myocardial dysfunction. Noninvasive Left Ventricular Myocardial Work in Patients with Chronic Aortic Regurgitation and Preserved Left Ventricular Ejection FractionJournal of the American Society of EchocardiographyVol. 35Issue 7PreviewLeft ventricular (LV) global longitudinal strain (GLS) has been proposed as a sensitive marker of myocardial damage in patients with chronic severe aortic regurgitation (AR) and preserved LV ejection fraction (LVEF). However, LV GLS does not take into account the afterload. Noninvasive LV myocardial work is a novel parameter of LV myocardial performance, which integrates measurements of myocardial deformation and noninvasive blood pressure (afterload). The aims of this study were (1) to assess noninvasive LV myocardial work in patients with chronic AR and preserved LVEF and its correlation with other echocardiographic parameters, (2) to evaluate changes of LV myocardial work after aortic valve replacement or repair (AVR), and (3) to assess the relationship between LV myocardial work and postoperative LV reverse remodeling. Full-Text PDF Open Access