The role of left atrial strain in patients with functional tricuspid regurgitation before and after annuloplasty: a long-term follow-up study

Functional tricuspid regurgitation (TR) is quite common in left heart disease, and several studies have confirmed that preoperative functional TR may progress if left untreated at the time of left-sided valve surgery. Selective tricuspid valve annuloplasty (TVA) can prevent TR from worsening and thus decrease both postoperative mortality and morbidity. However, even after the appropriate intervention, moderate-to-severe TR recurs in up to 15 to 20% of patients within the first year and in 30 to 70% of patients within 3–5 years and is closely related to increased mortality [1]. Previous studies have reported predictors of TR recurrence after annuloplasty, including right ventricular (RV) dysfunction, pulmonary hypertension, and preoperative tricuspid valve annular diameter. Interestingly, however, left atrial (LA) dysfunction has rarely been investigated in these situations. Park and colleagues reported that improvement of LA function after the maze procedure was strongly associated with a significantly decreased risk of late progression of TR [2]. Kim et al. also confirmed that the maintenance and recovery of LA mechanical function are valuable for preventing progression of functional TR in patients undergoing left-sided valve surgery [3]. However, these studies were mainly concerned with the effects of conventional echocardiographic parameters on functional TR, which have limited value in reflecting LA function. Several studies have noted that the LA strain, particularly reservoir strain, is crucial for non-invasive function assessment and may be valuable for clinical evaluation and earlier therapeutic intervention [4, 5]. The role of LA strain in patients with functional TR before and after TVA is still unknown. In this study, LA function was suggested to play crucial roles in the onset, development, and progression of functional TR. Whether combining preoperative LA strain with traditional echocardiographic indicators could be a better non-invasive tool for predicting TR recurrence also needs to be further investigated.

The present study had two major findings. First, preoperative functional TR severity was correlated with LA strain in rheumatic mitral stenosis patients; this is the first study to provide clear evidence of this association. Second, the preoperative LA reservoir strain and mean transmitral gradient were independent predictors of recurrent TR after TVA over long follow-up periods. Additionally, the AUC for the combination of the two indicators was 0.90, indicating that the combined indicators were more accurate than single indicators in predicting TR recurrence.

LA inflammation and fibrosis can be attributed to rheumatic carditis and lead to LA pressure overload. It is well known that these pathological and hemodynamic changes induce electrical and mechanical remodelling of the atrium and are closely related to subsequently increased pulmonary artery pressure, tricuspid annular dilatation, and functional TR development. Some researchers have shown that patients with rheumatic mitral stenosis are at increased risk of significant LA enlargement and dysfunction, and TR is relatively common (up to 55 to 60%) in these patients [11, 12]. Conversely, RV volume overload due to moderate-to-severe TR can result in left heart geometric alterations that reduce LA preload, impair left ventricular filling function, and decrease the atrial contribution to left ventricular filling [13, 14]. Thus, certain correlations between functional TR severity and LA function may exist. The present study demonstrates, on the one hand, that LA mechanics, including reservoir and conduit function, was markedly impaired in patients with rheumatic mitral stenosis. On the other hand, preoperative functional TR severity was found to correlate with LA strain in this study. The result suggests that LA functional changes are closely related to functional TR and supports our a priori hypothesis. A recent study in a population with severe pulmonary arterial hypertension also demonstrated decreased LA global strain and suggested that this reflects LA dysfunction in these patients [15]. Moreover, Ashwin et al. noted the exceptional value of LA strain in the diagnosis and treatment of pulmonary hypertension in their latest study [16]. All these findings indicate that LA strain has specific value in the diagnosis and assessment of right heart diseases; further research regarding the interrelationships among the right ventricle, pulmonary circulation, and left atrium is still needed.

TVA is a common strategy used for the treatment of significant functional TR, although reports of TR recurrence after the procedure exist. A 30 to 70% recurrence rate within 3 to 5 years can be reported even in the absence of organic changes, including infective endocarditis, degenerative changes, and rheumatic damage, and recurrence is associated with a poor prognosis [17, 18]. Therefore, relatively accurate predictors of TR recurrence are needed and are expected to provide substantial benefit to these patients. Some studies have reported that LA dilatation is an independent predictor of late TR recurrence during the follow-up period [19]. However, no investigators have focused on the value of LA strain. In the present study, LA reservoir strain was predictive of recurrence and had moderately high sensitivity and specificity. As we know, differing parameters regarding predictors of recurrence may reflect different causes of functional TR. LA reservoir function represents LA filling by pulmonary vein flow during ventricular systole and demonstrates stiffness of the left atrium, producing higher pressures. For example, LA reservoir strain has previously been correlated with left ventricular filling parameters and negatively correlated with mean pulmonary artery pressure and pulmonary capillary wedge pressure [20, 21]. Owing to the pathophysiological link between left-side heart diseases and the development of functional TR, the finding that recurrent TR could be predicted by parameters correlating with LA function can be explained. In the meantime, it is noteworthy that the damage to atrial function caused by the stenotic mitral orifice and active inflammatory lesions is already present before surgery. Even if a stenotic lesion is relieved, pulmonary vascular remodelling and elevated pulmonary vascular resistance may continue to occur and lead to morphological changes of the tricuspid valve and TR recurrence. Additionally, the relationship between LA reservoir strain and LAVI attracted our attention. In the present study, patients in Group II demonstrated lower value of atrial volume index in addition to lower reservoir atrial strain. The relationship is distinct from previous studies that have determined the inverse correlation between the two parameters [22]. This is probably because these patients have already developed a low flow state due to pulmonary vascular remodelling and irreversible obliterative changes. This pathophysiological change reduces congestive symptoms by decreasing venous return and leads to lower value of left atrial volume index, albeit at the expense of a reduction in cardiac output. However, further studies are needed to address this speculation. All these results suggest that surgeons should focus on correcting LA function disorders and reversing pulmonary vascular remodelling in rheumatic mitral stenosis patients undergoing MVR with concomitant TVA for functional TR to reduce recurrence effectively.

The present study also found that the preoperative mean transmitral gradient was an independent predictor of recurrence and had moderately high sensitivity and specificity. The mean transmitral gradient reflects changes in the degree of valve stenosis as well as LA compliance and cardiac output. A higher mean gradient, with an expected increase in PA pressure, could further change the tricuspid annular size and function. This is one possible reason to predict TR recurrence for the mean transmitral gradient. Jong-MinSong et al. studied 71 patients who suffered moderate-to-severe functional TR before percutaneous mitral valvuloplasty. The results indicated that functional TR could be reduced when the transmitral gradient was fully relieved, which also confirmed that changes in the transmitral pressure gradient could influence functional TR [23]. However, there are also conflicting reports indicating that the transmitral gradient (peak or mean) on follow-up echocardiographic assessment failed to predict recurrence of functional TR [24]. The surgical treatment of rheumatic mitral stenosis in our study differed from that in the previously mentioned studies. The long-term outcome of percutaneous mitral valvuloplasty may be influenced by the postoperative transmitral gradient. In contrast, the patients in our study underwent MVR surgery, and the postoperative transmitral gradient was within a reasonable and consistent range. The results may highlight the prognostic significance of the preoperative transmitral gradient. However, the usefulness of this information in the real world is still unknown because the choice of surgical procedure for patients could be affected by many influencing factors.

In the current study, the preoperative PASP was similar between the successful repair and recurrent groups and atrial fibrillation also had no significant effect on recurrence. This may have occurred because most patients included in this study had pulmonary hypertension and atrial fibrillation and had a relatively severe condition. Thus, there was no significant difference between the two groups in this regard. Meanwhile, some studies have noted that the development of postoperative PASP is also a matter of concern in patients who have undergone TVA and other cardiac procedures [25, 26]. However, given that a clear postoperative TR Doppler spectrum could not be obtained in several patients, this aspect cannot be demonstrated in the present study and required further exploration in future studies. In fact, determining the predictors or factors associated with recurrent functional TR after repair is a complicated topic because the results will likely be related to the underlying disease. In this study, rheumatic mitral stenosis was the dominant disease. It is known to cause secondary pulmonary hypertension, RV dysfunction, and functional TR. However, whether the findings could be applied to more routine forms of functional TR such as ischaemic cardiomyopathy or nonischaemic cardiomyopathy, where intrinsic RV dysfunction is greater, remains uncertain. Therefore, this is an important direction for future research to address.

Our study has several limitations. First, this study was a single-centre study, and the small cohort size and selection bias reduces the possibility of extensive analysis and subgroup comparisons. These results should be interpreted with caution. Moreover, follow-up was performed at the discretion of the physician caring for the patient and we did not explore effect of LA strain on long-term survival and predictors of complications and mortality. Thus, the conclusion of this study still requires verification in large, prospective, randomized studies. Second, we cannot guarantee that TR was functional and not related to rheumatic involvement of the tricuspid valve in all cases. However, during the last echocardiographic follow-up, an experienced ultrasound operator did not find direct evidence of rheumatic involvement of the tricuspid valve, indicating that the results were credible. Third, different TVA techniques may affect patients’ outcomes. However, in the present study, we found that there was no difference in TVA technique between the two groups. The improvement of surgical skills and similar state of disease could partly explain this result. Thus, we suggest that the TVA technique applied did not greatly affect the overall results and that a longer follow-up time is needed. Finally, the dependability of the LA strain is affected by operators and image quality and consumes more time for determination than conventional echocardiographic parameters. However, several studies have confirmed its reliability and provided normal reference values [27], making the LA strain a reliable parameter to use in future clinical practice.

LA strain was correlated with preoperative functional TR severity in patients with rheumatic mitral stenosis. In the multivariate analysis, the LA reservoir strain and preoperative mean transmitral gradient emerged as independent predictive factors for recurrent TR after TVA during long-term follow-up. The present study also noted that surgeons should focus on correcting LA function disorders and reversing pulmonary vascular remodelling to reduce TR recurrence for such patients.