Clip, Slip, and Grip

HomeCirculation: Cardiovascular ImagingVol. 11, No. 3Clip, Slip, and Grip Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBClip, Slip, and GripImpact on Left Atrial Strain Lili Zhang, MD, ScM and Cynthia C. Taub, MD Lili ZhangLili Zhang From the Division of Cardiology, Montefiore Medical Center, Bronx, NY. and Cynthia C. TaubCynthia C. Taub From the Division of Cardiology, Montefiore Medical Center, Bronx, NY. Originally published13 Mar 2018https://doi.org/10.1161/CIRCIMAGING.118.007491Circulation: Cardiovascular Imaging. 2018;11:e007491It's not that I'm so smart, it's just that I stay with problems longer—Albert EinsteinThe impact of severe organic mitral regurgitation (MR) on left atrium (LA) size and function has been studied; however, changes in LA function after mitral valve (MV) interventions remain unclear. In this issue of Circulation: Cardiovascular Imaging, Gucuk Ipek et al1 retrospectively studied LA and left ventricle (LV) strain by speckle-tracking echocardiography (STE) at baseline and at 12-month follow-up in 87 subjects with severe organic MR enrolled in the EVERST II trial (Endovascular Valve Edge-to-Edge Repair Study), including 49 patients who underwent MitraClip placement and 38 patients who underwent surgical MV repair (MVr). Their findings suggest that LA strain post-MV interventions is complicated and may be affected by multiple factors (Figure), including patient demographics, baseline LA size/function, treatment modalities and MR reduction, among others.Download figureDownload PowerPointFigure. Left atrium (LA) strain post-mitral valve (MV) interventions is affected by multiple factors. LV indicates left ventricle.See Article by Gucuk Ipek et alLA Size (Volume) and MROrganic MR can lead to chronic volume overload on LA and consequent remodeling, which is manifested as LA dilatation and LA dysfunction. LA becomes less compliant because of chronic inflammation, LA myocyte hypertrophy, interstitial fibrosis, and decreased matrix metalloproteinase expression.2 LA volume index ≥40 mL/m2 is an independent predictor of atrial fibrillation and combined end point of death or need for mitral surgery in patients with organic MR.3 Baseline LA volume index and its progressive increase can predict the development of symptoms and LV dysfunction in asymptomatic patients with moderate and severe organic MR.4 Baseline LA volume index was also shown to strongly predict survival independent of MR severity and other known risk factors, and mitral surgery was shown to markedly improve outcomes and restore life expectancy.5LA Function and MRLA function has been conventionally divided into 3 phases: (1) reservoir phase, LA stores pulmonary venous return during LV contraction and isovolumetric relaxation; (2) conduit phase, LA transfers blood passively into the LV; and (3) active contraction phase, LA contracts during the final phase of diastole, if with sinus rhythm.6 LA function can be assessed by LA volumes at different time points of the cardiac cycle, mitral inflow peak A velocity by pulsed wave Doppler interrogation, atrial systolic contribution to the total mitral inflow time velocity integral, and pulmonary venous atrial reversal velocity. In addition, LA ejection fraction, LA ejection force, LA kinetic energy, mitral annulus a′ velocity, strain, and strain rate by tissue Doppler imaging can be used to measure LA function.6,7STE is a sensitive technique for the assessment of myocardial deformation. It is considered relatively geometry independent and angle independent. There has been increasing evidence suggesting that STE is highly promising for regional and global LA function assessment.8 It was shown to detect subtle impairment of LA function at earlier stages before LA dilation occurs.9Peak atrial longitudinal strain (ε) and peak systolic strain rate represent reservoir function, corresponding to LA function between MV closure and MV opening. Peak early diastolic strain and strain rate represent conduit function, corresponding to LA function between MV opening and the onset of the A wave. Peak late diastolic strain and strain rate represent contractile function of LA during A-wave. A recent meta-analysis revealed a normal reference range for reservoir strain of 39% (38%–41%), for conduit strain of 23% (21%–25%), and for contractile strain of 17% (16%–19%) in 40 studies (2542 healthy subjects).10Impact of MR on LA StrainIn chronic severe organic MR, LA deformation indices derived from STE were found to be impaired and to provide incremental value in predicting the need for MV surgery and prognosis of chronic MR. LA deformation is significantly influenced by the degree of MR. Increase in LA strain at the reservoir phase was observed in patients with mild MR and, instead, a stepwise decline from moderate MR group to severe MR. Similarly, atrial contraction strain was found increased in the mild and moderate MR patients, whereas a significant depression was recorded in patients with severe MR.11 The increased reservoir and contractile function in early stage of MR is likely because of enhanced atrial compliance. In patients with severe MR, studies consistently demonstrated significant LA reservoir and contractile dysfunction, indicating persistent atrial stiffness and remodeling from chronic LA overloading.12–14 LA strain was shown to be an independent predictor for baseline functional status, need for mitral surgery, survival, reverse remodeling post-MV surgery, and postoperative atrial fibrillation.12–17 Peak atrial longitudinal strain is also strongly and independently correlated with LA fibrosis and endocardial thickness in patients with severe organic MR undergoing MV surgery.18 These studies support LA deformation as a surrogate marker for LA stiffness and remodeling before overt manifestation of LA structural changes.Mitral Clip and LA StrainMitraClip is the first Food and Drug Administration–approved transcatheter MVr system to reduce chronic, severe organic MR in patients who are not surgical candidates. The procedure attaches the clip on the regurgitant leaflets to imitate an Alfieri surgical repair. Previous studies have reported stable LV and right ventricle function and reduction in LV and LA volume in organic MR patients after MitraClip.19 In patients with baseline preserved LA function in sinus rhythm, improvement in LA conduit function and contractile function was reported after MitraClip.20Gucuk Ipek et al1 studied LA and LV strain by STE at baseline and at 12-month follow-up in patients with severe organic MR who underwent MitraClip and MVr. Clinical outcomes including MR reduction, quality of life, New York Heart Association classification, and adverse events (heart failure, atrial fibrillation, and cerebrovascular accidents) were also studied. They found that LA function after treatment of MR is dependent on baseline LA function, residual MR, LV function, and treatment modalities.First, based on the median LA reservoir strain (ε) of the cohort, the study classified patients into 2 groups (normal/high LA ε versus low LA ε). Patients were found to have older age, more heart failure history, and larger LA size in the group with impaired LA ε. Clinical outcomes were largely comparable in these 2 groups, despite a tendency of more adverse events in the group with impaired LA ε. The choice of using median LA ε to classify patients is rather arbitrary. Although the normal value of LA strain is debatable and may be vendor dependent, previous meta-analysis based on 40 studies reported mean LA reservoir strain as 39.4% (38.0%–40.8%). The current cutoff (30%) is much lower than the reported normal range, so may not be able to classify patients as with true normal or abnormal LA reservoir strain. If age- and sex-matched normal subjects were analyzed as controls in this study, the normal level of LA strain would be more reliable.An important finding of this study is that changes of LA reservoir strain were dependent on baseline LA ε and MR reduction. Significant LA ε reduction was observed in 2 scenarios: (1) in patients with normal/high baseline LA ε and successful MR reduction; and (2) in patients with low baseline LA ε and unsuccessful MR reduction. In the first case, LA reservoir function was preserved at baseline and its reduction after MitraClip or MVr was thought to be because of correction of LA overload after successful MR reduction. In the latter case, baseline low LA ε indicated LA stiffness and remodeling, suggesting the chronicity of LA dysfunction. LA reservoir function further deteriorated when MR was not corrected successfully.However, LA strain was measured at 12 months post-MitraClip or MVr; therefore, alteration to LA strain should not only be a result of change in LA loading condition, rather a reflection of reverse remodeling. In this study, patients with successful MR reduction had decreased LA size, a manifestation of LA reverse remodeling. Decreased LA ε from baseline, on the contrary, did not support reserve remodeling. Previous evidence, although limited, certainly revealed such a controversy with both decreased21 and improved20,22 LA strain post-mitral procedures. The potential mechanism of changes in LA strain is worth more discussion. Studies with larger sample size, further characterization of study population, and meticulous measurement of LA strain with reliable software are warranted for a more definitive answer to this question.In addition, this study found that at 12-month follow-up, peak early diastolic strain and strain rate was significantly decreased in both treatment arms. Decrease in peak early diastolic strain and strain rate was attributed to the presence of MitraClip. Other possible reasons include the decrease in LA filling pressure, improvement of MV effective regurgitant orifice area, and transmitral gradient after MVr or MitraClip. This revealed the objective benefit of decreasing MR, even with a residual MR >2+ grade. It supports the assumption that, even if not achieving an optimal result in terms of the reduction of MR grade, patient could still benefit from some degree of MR reduction. Further studies can be performed to investigate the correlation between peak early diastolic strain and strain rate and diastology indices, such as mitral flow E velocity, E deceleration time, E/A ratio, and E/e′ ratio. It would be also interesting to evaluate LA strain in relation to the effective regurgitant orifice area reduction in a larger patient cohort.Another interesting finding of this study is that LV global longitudinal strain was significantly decreased at 12 months in MVr patients, regardless of the baseline LA strain. This was not observed in MitraClip patients. The potential mechanism of this finding is the increased afterload of LV after successful MR reduction in MVr group. However, the significant impairment of LV strain (from −21.5±3.9% to −16.9±3.8%) after MVr is worrisome and probably cannot be explained by the change of hemodynamics alone. It is important to investigate if LV strain can recover after longer duration of follow-up. Several studies have reported the change of LV strain after mitral surgery, and the results tend to be controversial.23,24 This again implies that LV and LA strain changes after MV interventions are affected by the complicated interplay of patient population, MR types (functional versus organic), baseline LV and LA function, hemodynamics, etc.This study is relevant and hypothesis generating. Results of the current study need to be interpreted with careful considerations. First, patients included in the study were highly selective. They were younger, in sinus rhythm, with organic MR, less comorbidities, and normal baseline left ventricular ejection fraction (LV dysfunction may be subclinical). These patients are very different from those needing MitraClip in the real clinical setting; thus, generalization of the results could be problematic. Second, STE analysis was performed with commercial software designed for LV strain analysis, not for LA strain analysis. The technical challenges of LA strain analysis include accurate tracking of interatrial septum, pulmonary vein and LA appendage opening, image quality (shadowing from MV and annular calcifications), and electrocardiographic reference of cardiac cycle. The normal value of LA strain is vendor dependent, which makes the comparison across studies arduous. The intra- and interobserver variabilities were not reported in this study. Because of technical difficulties mentioned, it is essential to ensure that the measurements are reliable. The authors also commented on significant correlation between LA ε, LV ε, and the relative change in LA ε and LV ε at 12 months. However, low correlation coefficients (0.24–0.37) can only reveal very modest correlation. The statistical significance is probably overstated, and these results should be analyzed with caution.This study contributes to a better understanding of the changes of LA function after MitraClip in comparison with MVr in patients with organic MR.1 Future studies can focus on LA strain in correlation with other LA function measurements and diastology indices. Longer follow-up is needed to uncover sustained changes of LA and LV function after MV procedures and their association with clinical outcomes. Further investigation in patients selected from real clinical settings will be needed. Last, dedicated software designed to analyze LA strain, standardization of methodology, and intervendor comparison of LA strain softwares will be instrumental to further research endeavor in this area.DisclosuresNone.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Correspondence to Cynthia C. 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Wang D, Xu J, Chen X, Xu T, Zhang W, Li Y and Wang J Left atrial myocardial dysfunction in patients with primary as assessed by speckle-tracking of 11, 3 Article American Heart Originally and