Additional left atrial plication improves postoperative cardiovascular events in atrial functional mitral regurgitation

Introduction

Atrial fibrillation (AF) is an arrhythmic disease that affects more than 1.5 million people in Japan, and the number of patients continues to increase. Atrial cardiomyopathy, a condition in which atrial dysfunction progresses from persistent AF, has recently attracted considerable attention (1). In severe cases of atrial cardiomyopathy, atrial enlargement is followed by dilatation of the atrioventricular annulus, resulting in the development of mitral valve (MV) and tricuspid valve (TV) regurgitation (2-4). We previously reported that patients with severe atrial cardiomyopathy and enlarged atria are at a high risk of repeat hospitalization for heart failure and arrhythmic death (3,5). Furthermore, we have encountered many cases of biventricular regurgitation with giant atria that suffer from cardiovascular events (CVEs) such as heart failure and thromboembolism, even after MV and TV repair (5). Thus, a giant atrium is indicative of end-stage atrial cardiomyopathy. Based on this experience, as a multidisciplinary treatment for atrial cardiomyopathy, we have aggressively performed concomitant left atrial (LA) plication as a measure to correct remodeling since 2018 and have been believed to improve prognosis in advanced atrial cardiomyopathy. This study aimed to elucidate the efficacy of concomitant LA plication during MV repair in patients with atrial functional mitral regurgitation (MR) and tricuspid regurgitation (TR). We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-593/rc).

Methods

Between October 2008 and August 2023, we performed 952 cases of MV repair at Osaka Metropolitan University Hospital and Osaka City General Hospital. Of these, we performed MV repair and concomitant TV repair for atrial functional MR and TR in 74 patients complicated with permanent AF and preserved left ventricle (LV) systolic function with LV ejection fraction (LVEF) >50%. All patients underwent mitral and tricuspid annuloplasty. Of 74 patients, 17 were additionally treated with posterior mitral leaflet patch augmentation (6), and 28 with pseudoprolapse of the anterior leaflet were additionally treated with chordal reconstruction using loop technique (4,7,8). Nineteen patients underwent the Maze procedure and 26 patients underwent LA plication. LA plication with closure of the left atrium appendage has been performed as much as possible since 2018. According to the consensus of the Department of Cardiology and Department of Cardiovascular Surgery of our hospitals, MV repair and concomitant TV repair were performed in patients with (I) permanent AF that had persisted for >1 year, (II) preserved LVEF of 50%), (III) at least one prior admission for acute decompensated heart failure complicated by severe functional MR, and (IV) chronic heart failure symptoms of at least New York Heart Association (NYHA) functional class II. Patients with apparent degenerative changes in the MV (Carpentier type II and IIIa), regional LV wall motion abnormalities suggestive of myocardial ischemia or infarction (Carpentier type IIIb) or dilated cardiomyopathy were excluded from the study. Patients with a confirmed diagnosis of cardiomyopathy or a history of cardiac surgery were also excluded. The patient selection process is shown in Figure 1A. Data on patients’ clinical characteristics, symptoms and echocardiographic parameters before and after surgery were retrospectively collected from medical records and analysed. The Institutional Review Board of Osaka Metropolitan University Hospital approved the data analysis for this retrospective study and waived the requirement for patient consent (approval No. 2024-024). The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).

Figure 1 A flow diagram and figure of left appendage closure were shown. (A) A flow diagram illustrating the selection of the final study cohort. (B) Left atrial appendage closure followed by para-annular LA plication. ePTFE sutures from the inside of LA was used. LA plication was subsequently performed using expanded ePTFE sutures at the left atrial appendage closure and proceeded along the para-annular line to the caudal right-sided atriotomy line or septal approach line. ePTFE, expanded polytetrafluoroethylene; LA, left atrium; MR, mitral regurgitation; MV, mitral valve; EF, ejection fraction; AF, atrial fibrillation; TR, tricuspid regurgitation; TAP, tricuspid annuloplasty.

Echocardiography

All patients underwent transthoracic and transoesophageal echocardiography within one week preoperatively, immediately postoperatively and every 12 months thereafter at our institution. MR severity was defined using a multiparametric approach that included assessment of colour Doppler-derived jet area, effective regurgitant orifice area using the proximal isovelocity surface area method, MR volume and fraction using the Doppler-derived volumetric method. TR grading was based on colour Doppler-derived jet area, continuous wave Doppler-derived jet density and contour, and defined using a multi-parametric approach including assessment of hepatic venous flow velocity patterns. For all measurements of systolic parameters in patients with AF, beats occurring after two consecutive beats of mean R-R interval were carefully selected (9). For statistical analysis, MR or TR was assessed according to the following scores: none =0, none to mild =0.5, mild =1, mild to moderate =1.5, moderate =2, moderate to severe =2.5 and severe =3 (3).

MV repair and annuloplasty

Cardiopulmonary bypass was established by a median sternotomy with ascending aortic cannulation and bilcaval venous return, and MV was carefully observed by a transseptal or left-sided atrial approach. All patients underwent MV repair. After intercommissural distance and anterior MV sizing, an annuloplasty ring (Carpentier Edwards Physioring or Physioring II; Edwards Lifesciences, Irvine, CA, USA) was implanted. If there was a large gap between the anterior and posterior leaflet of the MV due to severe posterior leaflet tethering, an autologous pericardial patch augmentation of posterior leaflet was performed. If psuedoprolapse of the anterior leaflet was observed, chordal reconstruction of the anterior leaflet was performed at the surgeon’s discretion. All patients underwent concomitant TV annuloplasty with MC3 ring (Edwards Lifesciences) or Cosgrove-Edwards annuloplasty ring (Edwards Lifesciences).

Left appendage closure and LA plication

The LA appendage was closed using expanded polytetrafluoroethylene (ePTFE) sutures. LA plication was subsequently performed using ePTFE sutures with LA appendage closure and proceeded along the para-annular line to the right atriotomy line or the septal approach line (Figure 1B).

Measurement of the protruding posterior LA length, aortomitral (AM) angle, posterior leaflet coaptation angle, and posterior leaflet tip angle

AM complex measurements were evaluated in mid-systole using the long-axis view. The protruding posterior LA length was measured from the posterior mitral annulus to the LA posterior wall in contact with the pericardium as an indicator of hamstringing of the MV complex (5,10) (Figure 2A). The posterior leaflet coaptation and tip angles were defined as the angles comprising the annular line and the line drawn between the anterior or posterior annulus and the coaptation or tip of the posterior leaflet, respectively (Figure 2B). Postoperative posterior leaflet coaptation angle was defined as the angle between the annular line and the line drawn between the posterior annulus and the coaptation of the posterior leaflet (Figure 2C). The AM angle was defined as the angle between the mitral and aortic annulus planes in the parasternal long-axis view (Figure 2D). To determine the difference between the preoperative and postoperative AM angles, the postoperative AM angle divided by the preoperative AM angle was evaluated. The A2 and P2 leaflet lengths and the mitral anterior and posterior leaflet angles were also measured at midsystole.

Figure 2 Measurements of parameters by echocardiography were shown. (A) The length of the posterior protruding LA distance was measured from the posterior mitral annulus to the LA posterior wall contacting the pericardium as an indicator of the hamstringing phenomenon of the MV complex. Blue circle indicates posterior mitral annulus. Yellow arrows indicate posterior protruding LA length. (B) The posterior leaflet coaptation and tip angles were defined as the angles comprising the annular line and coaptation (angle in red) or the tip of the posterior leaflet (angle in yellow), respectively. The anterior leaflet coaptation angle was defined as the angles comprising the annular line and coaptation of the anterior leaflet (angle in blue). (C) Postoperative posterior leaflet coaptation angle was defined as the angles comprising the annular line and the line drawn coaptation of the posterior leaflet (angle in red). (D) The AM angle was defined as the angle between the mitral annulus plane and the aortic annulus plane in the parasternal long-axis view (angle in blue). MV, mitral valve; LA, left atrium; AM, aortomitral.

Follow-up examination and management

Post-operative follow-up was carried out in clinics, outpatient clinics and by telephone survey. Follow-up was completed by all patients and ranged from 15 to 4,156 days (median 1,410 days). Postoperative follow-up with echocardiography was performed at our hospital on postoperative days 7–14 and every 3–6 months after discharge. The follow-up period ranged from 15 to 4,156 days, with a median of 648 days.

Data collection and statistical analysis

Descriptive statistics for categorical variables were reported as absolute values and percentages, while continuous variables were presented as means and standard deviations. Receiver operating characteristic curves and area under the curve were assessed using standard methods. The optimal cut-off value was defined as the value with the highest sum of sensitivity and specificity. Morbidity rates were modelled using survival analysis with the Kaplan-Meier product-limit method and the Cox proportional hazards model. The event-free rates were estimated using the Kaplan-Meier product-limit method and compared using the log-rank test. Univariate linear regression analysis was performed to analyse independent determinants of postoperative qualitative posterior leaflet angle, with P values of 0.05 and 0.10 for inclusion and exclusion from the model, respectively. Statistical analyses were performed using R version 3.3.2 (R Foundation for Statistical Computing, Vienna, Austria). Statistical significance was set at P<0.05.

Results

Patient’s selection

The patient’s selection is shown in Figure 1A. Of the 952 patients who underwent MV surgery, 243 (26%) were in persistent AF at the time of surgery and 709 (74%) were in sinus or other rhythm. Of the 243 patients with persistent AF, 145 had degenerative MR, four had ischemic MR, 12 had ventricular functional MR with ejection fraction <50% without ischemic change, three had infective endocarditis and five had rheumatic MR. We performed simple MV replacement and tricuspid valve annuloplasty (TAP) only in eight patients with MR of mixed etiology with moderate operative risk (e.g., due to old age) and/or functional and organic changes. The remaining 74 patients with functional atrial MR and TR who underwent MV repair and TAP constituted the final study cohort.

Preoperative characteristics and echocardiographic data in patients with LA plication and patients without plication

Patient profiles are shown in Table 1. More patients had LA plication complicated by hypertension than patients without LA plication (P=0.002). The AM angle in patients with LA plication was more acute than those without LA plication (112°±9.0° vs. 115°±7.4°, P=0.03). There were no significant differences between the groups in A2 and P2 height, protruding posterior LA length, posterior leaflet coaptation angle, posterior leaflet tip angle, or LV dimensions.

Surgical procedures and postoperative echocardiographic data in patients with LA plication and patients without plication

The peri-operative and post-operative echocardiographic data are summarized in Table 2. MV ring size in patients with LA plication was larger than that in patients without LA plication (30±2.6 vs. 29±2.3 mm, P=0.02). LVEF after surgery in patients with LA plication was lower than that in patients without LA plication (57%±4.5% vs. 60%±6.8%, P=0.02). The protruding posterior LA length at mid-term periods in patients with LA plication was shorter than that in patients without LA plication (2.8±0.49 vs. 3.3±0.72 cm, P=0.01). The AM angle in most recent periods divided by preoperative AM angle in patients with LA plication was bigger than that in patients without LA plication (1.04°±0.102° vs. 0.98°±0.084°, P=0.01). The posterior leaflet coaptation angle in mid-term periods in patients with LA plication was smaller than that in patients without LA plication (42°±15° vs. 76°±30°, P<0.001).

Predictors of postoperative CVEs in patients without LA plication

There were 48 patients who did not undergo LA plication. Univariate Cox proportional hazard regression analyses were performed to determine the risk factors for postoperative CVEs in patients without LA plication. Among all preoperative echocardiographic parameters, the preoperative left atrial volume index (LAVI), protruding posterior LA length, and TR grading score were predictors of postoperative CVEs. Among all the peri-operative parameters, posterior leaflet extension (PLE) was a predictor of postoperative CVEs. Among all the postoperative echocardiographic parameters, LAVI, protruding posterior LA length, AM angle, and posterior leaflet coaptation angle were predictors of postoperative CVEs. Among all echocardiographic parameters in the midterm period, LAVI, protruding posterior LA length, and posterior leaflet coaptation angle were predictors of postoperative CVEs. According to the multivariate Cox proportional hazards regression analysis, the preoperative protruding posterior LA length, preoperative TR score, postoperative protruding posterior LA length, and posterior leaflet coaptation angle in the mid-term period were independent predictors of postoperative CVEs (Table 3).

Determinants of postoperative posterior leaflet coaptation angle

The determinants of postoperative posterior leaflet coaptation angle were shown in Table 4.

Univariate linear regression analyses showed that LA plication, preoperative EF, protruding posterior LA length, postoperative EF, postoperative LAVI, and postoperative protruding posterior LA length were positively associated with posterior leaflet coaptation angle.

Posterior leaflet coaptation angle as a factor influencing CVEs

To assess the optimal cut-off value of the post-operative leaflet angle for post-operative CVEs, a receiver operating characteristic curve was used for all patients (Figure 3A). The sensitivity and specificity for predicting post-operative CVEs were highest for a post-operative leaflet angle of 101° (62.5% and 98.1%, respectively). Kaplan-Meier analysis showed that patients with a post-operative leaflet angle of 101° or greater had a worse prognosis than those with a post-operative angle of less than 101°, with event-free rates at 3 years of 27% versus 93% at 5 years, 18% versus 80% at 7 years (P<0.001) (Figure 3B).

Figure 3 Receiver operating characteristic curves and Kaplan-Meier analysis were shown. (A) Receiver operating characteristic curves were used to evaluate the optimal cutoff value of the postoperative posterior leaflet coaptation angle for CVEs after surgery. A postoperative posterior leaflet angle of 101° had the maximum sum of sensitivity and specificity for predicting postoperative CVEs 62.5% and 98.1%, respectively. The area under the curve was 0.87. (B) Kaplan-Meier analysis showed that patients with a postoperative posterior leaflet coaptation angle of ≥101° had a poorer prognosis than those with a postoperative posterior leaflet coaptation angle of <101°, with an event-free rate of 64% vs. 93% at 3 years after surgery, 27% vs. 93% at 5 years after surgery, and 18% vs. 80% at 7 years after surgery, respectively (P<0.001). CVE, cardiovascular events; LAP, left atrial plication.

Freedom from CVEs with or without LA plication in patients without PLE (Figure 4A) and freedom from CVEs with or without LA plication in patients with PLE (Figure 4B)

Figure 4 Kaplan-Meier analysis was shown. (A) Kaplan-Meier analysis showed freedom from CVEs was not different between the two mitral annular plication alone groups with or without LA plication, with an event-free rate of 91% vs. 94% in 3 year and 72% vs. 94% in 5 years, and 94% vs. 62% in 7 years, respectively (P=0.18). (B) Freedom from CVEs was not different between the two mitral annular plication with additional posterior leaflet extension groups with or without LA plication, with an event-free rate of 62% vs. 83% in 3 year and 52% vs. 83% in 5 years, respectively (P=0.27). CVE, cardiovascular event; LA, left atrium; MAP, mitral annular plication; LAP, left atrial plication; PLE, posterior leaflet patch extension.

Kaplan-Meier analysis showed freedom from CVEs was not different between the mitral annular plication alone and mitral annular plication with LA plication groups, with an event-free rate of 91% vs. 94% in 3 years, 72% vs. 94% in 5 years, and 94% vs. 62% in 7 years, respectively (P=0.18). Kaplan-Meier analysis showed freedom from CVEs was not different between mitral annular plication + PLE groups and mitral annular plication + PLE with LA plication, with an event-free rates of 62% vs. 83% at 3 years and 52% vs. 83% at 5 years, respectively (P=0.27).

Discussion

Our data showed the following findings: (I) patients who underwent LA plication had a shorter postoperative protruding posterior LA length, a more obtuse postoperative AM angle and a narrower posterior leaflet coaptation angle than those who did not undergo LA plication; (II) postoperative posterior leaflet coaptation angle is a strong independent predictor of postoperative CVE; (III) patients with a postoperative posterior leaflet coaptation angle greater than 101° had a poor prognosis; (IV) freedom from CVE by LA plication tended to reduce postoperative CVE in the midterm period.

Several reports have suggested that surgical treatment of atrial functional MR may improve the prognosis (3,4,8,11). Abe et al. reported a 2-year event free rate of 21% in patients with significant MR and TR who were followed up with medical therapy alone (12). Based on this evidence, we performed aggressive surgical treatment for atrial functional MR and TR. Although both MV repair and TV repair are essential procedures, freedom from the CVEs was 52% at 5 years after surgery, which is considered to be unsatisfactory (13). Several studies have suggested that LA plication may be useful for determining the AM angle (14-17). Matsumori et al. reported satisfactory surgical results of atrial functional MR with LA plication, which may be appropriate for correcting the angle of a horizontally tilted (14). Nakamae et al. hypothesized that a giant LA might compress the posterior LV and aggravate diastolic dysfunction and heart failure. Additional LA plication contributes to the control of atrial functional MR and heart failure at later stages (15). We have also reported that a postoperative acute AM angle may increase the incidence of postoperative CVEs, indicating that LA plication might be a useful procedure to correct the AM angle (3). Consequently, LA plication is now being aggressively performed as an additional procedure.

In severe mitral valvular disease with a giant LA, abnormal findings such as compression and bending of the basal portion of the posterior wall of the LV are accompanied by paradoxical movement (18). Following MV replacement in this group of patients, the strut of the artificial valve was apt to lean against the ventricular septum, and the inflow stream of blood was directed toward the outflow tract of the LV, which appeared to be obstructed by the ventricular septum. By additional para-annular LA plication, compression and bending of the basal portion of the posterior wall of the LV and paradoxical movement were relieved. The abnormal angle of the MV was corrected and the inflow stream of blood was directed toward the apex of the ventricle in the usual manner. The overall operative result for a giant LA was markedly improved by this procedure (18). Nakashima et al. demonstrated two different directions of vortex, a “Clockwise” direction like the physiological vortex and a “Counterclockwise” direction. In systole, the loss ratio in the “Counterclockwise” vortex flow was significantly higher than that of “Clockwise” vortex flow. It is important to pay attention to the direction of the vortex in the ventricular chamber after MV surgery (19). LA plication might correct vortex flow from Counterclockwise direction to Clockwise direction, resulting in reducing the post-operative CVEs. Enomoto et al. performed blood flow analysis using computational fluid dynamics in the LA after LA plication. Blood flow stagnation was noted in the LA appendage, and an enlarged LA was also observed. The analysis revealed that LA plication for an enlarged LA improved blood flow stagnation more than virtual LA appendage resection alone (17).

Zhu et al. have reported the mechanism of persistent ischemic MR after annuloplasty. Anterior and posterior leaflet tethering, but with predominant and augmented posterior leaflet tethering, are related to persistent recurrent MR after annuloplasty. In recurrent MR cases, an anteriorly hoisted posterior mitral annulus using ring annuloplasty increases the posterior leaflet coaptation angle (20). Their posterior leaflet coaptation angle changed from 57°±9° to 111°±13°. Our data showed that posterior leaflet coaptation angle changed from 24°±9.0° to 76°±30° in patients without LA plication. One patient with recurrent severe MR had 130° after annuloplasty, resulting severe posterior tethering. The hamstring phenomenon of the posterior leaflet might occur not only in ischemic MR patients but also in atrial functional MR. We showed that the post-operative posterior leaflet coaptation angle is a strong predictor of postoperative CVEs. LA plication corrected postoperative posterior leaflet coaptation angle which changed only from 24°±13° to 42°±15°. Interestingly, our study showed that additional LA plication might improve surgical results in patients with mitral annuloplasty alone and mitral annuloplasty with patch augmentation. Additional LA plication can correct the AM angle, insulting the posterior leaflet coaptation angle in a more normal direction. Although long-term results are necessary, additional LA plication is the standard procedure for patients with atrial functional MR.

There are two main methods of left atrial plication. One is to suture the left atrium from the inside without resecting the left atrium (14), the other is to resect the LA appendage and left atrium (21-23). The methods of resection vary, with the radical method removing the left atrium around the MV and pulmonary vein (21). Complete resection has the advantage that there is no risk of residual blood flow in the follow-up period, but there is a risk of intraoperative hemorrhage. In giant LA cases, the LA wall is sometimes very thin. We have adopted the basic technique of left atrial plication without resection of the left atrium, considering the risk of hemorrhage.

Limitations

Our study had several limitations. First, our study was retrospective and the number of patients included was small. Nevertheless, our data were obtained from a single-reference surgical team committed to attempting valve repair using functional atrial MR and TR. Second, there might have been measurement bias regarding transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) cardiac parameters. Third, prior to 2018, left atrial plication was not actively performed; therefore, a random assignment was not possible. Finally, the patients included in the study were not homogeneous as they had various LA volumes.

Conclusions

Additional LA plication may be a useful procedure in patients with atrial functional MR and TR in terms of reducing postoperative CVEs.

Acknowledgments

We would like to thank Editage (www.editage.jp) for the English language editing.

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-593/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-593/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-593/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-593/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The Institutional Review Board of Osaka Metropolitan University Hospital approved the data analysis for this retrospective study and waived the requirement for patient consent (approval No. 2024-024). The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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