DOI:https://doi-xx.org/1050/17697021576260
Hong-Zhi Zuo1,a Jing-wen Gu2,b Ying-Long Lai1,c*
1Department of Cardiac Macrovascular Surgery, Affiliated Hospital of North Sichuan Medical College,Nanchong,637000,Sichuan, China
2Department of Thyroid and Breast Surgery ,Affiliated Hospital of North Sichuan Medical College,Nanchong,637000,Sichuan, China
aEmail: zuohongzhi0625@163.com
Abstract
Background: Degenerative mitral regurgitation (MR) leads to chronic volume overload, elevated left atrial pressure (LAP), and progressive atrial remodeling, but the relationship between hemodynamic unloading and left atrial (LA) structural and functional recovery after mitral valve (MV) repair remains incompletely defined.
Methods: In this single-center prospective cohort, 182 patients with severe degenerative MR scheduled for surgical MV repair were screened; 162 met inclusion criteria and 154 (95.1%) completed all hemodynamic and echocardiographic follow-up and formed the final analytic cohort. Invasive LAP was measured at baseline, immediately post-repair, and at 6 months. Comprehensive transthoracic echocardiography with LA strain analysis was performed at baseline, 3 months, and 6 months. The primary endpoint was change in mean LAP from baseline to 6 months. Secondary endpoints included changes in indexed LA volume (LAVi), LA phasic strain, LA stiffness, and clinical outcomes. Multivariable models were used to identify predictors of reverse remodeling.
Results: Mean LAP decreased from 23.6 5.8 mmHg at baseline to 15.1 4.7 mmHg postoperatively and 12.4 3.9 mmHg at 6 months (overall reduction 47.5%; p0.001). Peak v-wave pressure fell from 38.2 9.3 to 21.5 6.4 mmHg, and the LA compliance index increased from 1.12 0.34 to 1.48 0.38 (p0.001). LAVi declined from 62.4 14.8 to 48.7 12.6 mL/m (relative reduction 21.9%), with 94 patients (61.0%) meeting criteria for structural reverse remodeling. LA reservoir strain improved from 20.3 5.1% to 26.8 6.0%, and LA stiffness index decreased from 0.54 0.18 to 0.38 0.14 (both p0.001); 88 patients (57.1%) achieved functional reverse remodeling. At 6 months, 118 patients (76.6%) improved in New York Heart Association class, 62 (40.3%) by classes, whereas new-onset atrial fibrillation and heart failure hospitalization occurred in 7.1% and 5.8%, respectively. No deaths were observed.
Conclusions: Surgical repair of severe degenerative MR produces substantial and sustained reductions in LAP, accompanied by significant LA structural and functional reverse remodeling and favorable early clinical outcomes. These findings highlight the importance of timely MV repair and support comprehensive LA assessment, including strain imaging and hemodynamic evaluation, for risk stratification and postoperative monitoring.
Keywords: Mitral valve repair; Left atrial pressure; Atrial remodeling; Echocardiography; Hemodynamics; Prospective cohort
1 Introduction
Degenerative mitral regurgitation (MR) represents the most common form of primary valvular heart disease in industrialized nations and remains a major contributor to morbidity, atrial dysfunction, and long-term cardiovascular risk. Its prevalence increases markedly with age, affecting more than 10% of individuals older than 75 years and contributing to progressive cardiac remodeling and symptomatic deterioration in untreated patients. Chronic MR imposes a sustained volume load on both the left ventricle and left atrium (LA), leading to chamber dilation, rising left atrial pressure (LAP), and the development of a progressive atrial myopathy characterized by impaired compliance, mechanical dysfunction, and increased susceptibility to atrial fibrillation. These processes not only influence symptoms and functional capacity but also carry important prognostic implications, as demonstrated in recent studies examining the evolution of atrial remodeling in MR and related disease states [1,2].
The mechanistic cascade underlying atrial remodeling in MR begins with chronic volume overload, which leads to LA enlargement and elevated filling pressures. Over time, this adaptive enlargement transitions into maladaptive remodeling, marked by reduced compliance, increased stiffness, and impaired reservoir, conduit, and contractile function. A growing body of literature has underscored the relevance of LA phasic strain metrics—particularly reservoir strain—as sensitive markers of atrial dysfunction and predictors of postoperative outcomes in MR. Stassen et al. demonstrated that progressive deterioration in LA reservoir function correlates with adverse outcomes following mitral valve repair, emphasizing the prognostic significance of myocardial deformation indices beyond chamber size alone [3,4]. Similar pathophysiologic mechanisms have been described in patients with atrial functional MR and combined valvular lesions, where the interplay between pressure overload, atrial dilation, and myocardial fibrosis creates a substrate for persistent atrial dysfunction [5,6]. Collectively, these findings underscore the importance of understanding not merely the presence of atrial enlargement, but the mechanistic consequences of impaired compliance and rising LAP.
LA compliance and stiffness occupy a central role in this mechanistic framework. As volume and pressure overload progress, collagen deposition, extracellular matrix remodeling, and myocyte stretch lead to an increasingly stiff atrium, limiting reservoir capacity and impairing early diastolic conduit function. Advanced imaging modalities have enabled increasingly granular phenotyping of these changes, with speckle-tracking echocardiography offering insights into reservoir, conduit, and contractile phases of atrial deformation. This is particularly relevant because strain abnormalities may precede overt structural remodeling, providing clinicians with early markers of atrial dysfunction that could refine timing of intervention. Recent studies examining atrial fibrosis in mitral valve prolapse [7] and the role of atrial remodeling in rheumatic heart disease [8] further reinforce the connection between chronic volume overload, progressive stiffness, and functional impairment. Likewise, sex-specific patterns of remodeling and variations in LA–LV coupling in primary and secondary MR have been reported, expanding the conceptual understanding of how structural and functional remodeling interact across disease phenotypes [9–11].
Despite the growing understanding of LA remodeling mechanisms, several knowledge gaps persist. First, only a limited number of studies have simultaneously evaluated invasive LAP—an essential physiologic marker of atrial load—and advanced metrics of LA function such as phasic strain. Most available evidence relies solely on noninvasive surrogates, which may not capture subtle yet clinically meaningful hemodynamic changes. Second, prior studies have variably focused on early or late remodeling following mitral valve repair, with few providing a detailed trajectory of both early postoperative unloading and subsequent structural and functional recovery. As shown in observational analyses of surgical and transcatheter interventions, remodeling is neither instantaneous nor uniform; it occurs across multiple time scales and is shaped by baseline atrial characteristics, the extent of fibrosis, and the effectiveness of MR correction. However, few high-quality prospective cohorts have integrated hemodynamic, structural, and deformation-based measures to provide a comprehensive assessment of remodeling over time. Third, there is limited evidence regarding predictors of LA recovery following surgical correction of degenerative MR. While LA size, strain, and MR severity have each demonstrated prognostic relevance, multidimensional predictors—particularly the combined roles of LAP, compliance, and deformation—remain inadequately characterized. The absence of such integrated analyses represents a major gap in the ability to stratify patients, optimize surgical timing, and inform postoperative surveillance strategies.
Against this background, the present study was designed to address these unmet needs by prospectively evaluating the hemodynamic, structural, and functional consequences of mitral valve repair in a well-characterized cohort with severe degenerative MR. The primary objective was to quantify the change in mean LAP from baseline to 6 months following surgical repair, using a standardized invasive hemodynamic protocol. The secondary objectives were to assess: (1) structural remodeling as reflected by changes in indexed LA volume, (2) functional remodeling using reservoir, conduit, and contractile strain components, and (3) clinical outcomes including functional class and arrhythmia progression. We further sought to identify baseline hemodynamic and imaging predictors of reverse remodeling.
We hypothesized that surgical mitral valve repair would lead to substantial reductions in LAP, accompanied by meaningful structural and functional reverse remodeling of the LA. Specifically, we anticipated that hemodynamic unloading would result in improved atrial compliance, reductions in LAVi, and recovery of phasic strain components. By integrating invasive pressure measurements with advanced atrial functional metrics, this study aims to provide a comprehensive understanding of the trajectory and determinants of atrial remodeling following correction of chronic MR, addressing key evidence gaps identified in recent literature.
2 Methods
2.1 Study Design and Ethical Considerations
This study was designed as a single-center, prospective cohort investigation conducted at a high-volume tertiary cardiac surgery institution with long-standing expertise in degenerative mitral valve (MV) repair. Consecutive patients referred for elective surgical correction of severe primary mitral regurgitation (MR) were screened prospectively to minimize selection bias and ensure representative enrollment. A uniform perioperative protocol for hemodynamic monitoring and imaging acquisition was implemented across all participants to enhance internal validity.
Prior to participation, all patients provided written informed consent after receiving detailed verbal and written explanations of the study objectives, procedures, and follow-up requirements. The study adhered strictly to the ethical principles outlined in the Declaration of Helsinki and complied with institutional and national research regulations. The full study protocol, including predefined endpoints and a detailed statistical analysis plan, was reviewed and approved by the institutional research ethics committee. The analysis plan was finalized before patient recruitment and data collection to avoid analytical bias. Data confidentiality and patient privacy were preserved through coded identifiers and secure data storage throughout the study period.
2.2 Patient Population
Adults aged 18–85 years with severe, symptomatic or asymptomatic primary (degenerative) MR and preserved or mildly reduced left ventricular ejection fraction (LVEF ) were eligible for inclusion [12-13]. Severe MR was defined using an integrative multiparametric echocardiographic approach in accordance with current American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines. Eligible patients were required to be scheduled for elective isolated MV repair, with concomitant tricuspid repair permitted when clinically indicated.
Exclusion criteria were deliberately stringent to ensure a pathophysiologically homogenous cohort and included: (1) functional or ischemic MR; (2) any prior MV intervention; (3) moderate-to-severe disease of other cardiac valves requiring replacement rather than repair; (4) known infiltrative, inflammatory, or hypertrophic cardiomyopathies; (5) chronic atrial fibrillation (AF) with uncontrolled ventricular rate or long-standing persistent AF; (6) LVEF ; (7) severe pulmonary hypertension unrelated to MR; and (8) inability to complete planned follow-up or imaging studies due to logistical or physical limitations. The inclusion and exclusion criteria are summarized in Table 1.
Patients were enrolled consecutively over a 30-month period to capture real-world variability in clinical presentation while maintaining prospective rigor. Baseline demographic, clinical, laboratory, hemodynamic, and echocardiographic data were collected within 24 hours before surgery by trained research personnel. Follow-up assessments were performed at standardized intervals: postoperative day 1, 3 months, and 6 months. Only patients with at least one postoperative invasive hemodynamic assessment and paired baseline and 6-month echocardiographic measurements were included in the final analytic cohort to ensure completeness of primary and secondary endpoints.
Inclusion and Exclusion Criteria
| Category | Criteria |
| Inclusion | Severe degenerative MR; age 18–85; LVEF ; sinus rhythm or paroxysmal AF; suitability for surgical MV repair; ability to complete follow-up imaging. |
| Exclusion | Functional/ischemic MR; prior MV surgery; severe concomitant valvular disease; cardiomyopathy or infiltrative disease; chronic AF with rapid rate; LVEF ; inadequate echocardiographic windows; follow-up noncompliance. |
2.3 Surgical Procedure
All MV repair procedures were performed by experienced surgeons who specialize in reconstructive mitral surgery and perform more than 100 MV repairs annually [14]. A standardized operative technique was adopted to reduce inter-operator variability. Surgery was conducted under general anesthesia using conventional cardiopulmonary bypass with mild systemic hypothermia (32–34C) and intermittent antegrade cold blood cardioplegia for myocardial protection.
The choice of repair strategy was individualized based on leaflet pathology, annular morphology, and mechanisms of MR determined by intraoperative valve analysis. Techniques included triangular or quadrangular resection for posterior leaflet prolapse, artificial chordae implantation with expanded polytetrafluoroethylene sutures for anterior or bileaflet prolapse, sliding leaflet plasty for extensive posterior leaflet redundancy, and commissuroplasty when indicated. Annuloplasty was routinely performed using a semi-rigid or complete ring sized according to anterior leaflet height to restore annular geometry and prevent recurrent MR.
Intraoperative transesophageal echocardiography (TEE) was used systematically to confirm repair adequacy. Residual MR greater than mild, evidence of systolic anterior motion, excessive transmitral gradient, or suboptimal leaflet coaptation prompted immediate revision before chest closure. This quality-assurance protocol ensured that the initial surgical result was optimized and standardized across the cohort, thereby improving the interpretability of postoperative atrial remodeling outcomes.
2.4 Hemodynamic Assessment of Left Atrial Pressure
Left atrial pressure (LAP) was measured invasively using a fluid-filled, zero-referenced transducer system connected to a surgically placed left atrial catheter. The transducer was leveled at the mid-axillary line and calibrated before each measurement to ensure accuracy. Hemodynamic recordings were obtained at four predefined time points: (1) baseline, after induction of anesthesia but prior to initiation of cardiopulmonary bypass; (2) immediately following completion of MV repair and weaning from bypass, before chest closure; (3) postoperative day 1 under stable clinical conditions; and (4) six-month follow-up using percutaneous pulmonary artery catheterization [15].
For each time point, three key hemodynamic parameters were recorded: mean LAP, peak v-wave amplitude, and the LA compliance index. The compliance index was calculated as stroke volume divided by the difference between v-wave pressure and mean LAP, providing an indirect measure of atrial stiffness and chamber adaptability. Measurements were recorded during end-expiration and averaged over at least three cardiac cycles in patients with sinus rhythm. In patients with arrhythmias, especially atrial fibrillation or frequent ectopic beats, beat-by-beat measurements over ten consecutive cycles were averaged to reduce noise and improve reliability.
When direct invasive LAP measurement was clinically contraindicated or technically infeasible at follow-up, pulmonary capillary wedge pressure (PCWP) was obtained as a validated surrogate. PCWP values were accepted only when a previously established patient-specific calibration curve demonstrated strong correlation with invasive LAP at baseline. Regression-adjusted PCWP values were included exclusively in sensitivity analyses to avoid introducing measurement bias into the primary results.
All hemodynamic recordings were reviewed by a blinded cardiologist experienced in invasive pressure waveform interpretation. Recordings demonstrating damping, catheter whip, or respiratory artifact were excluded from analysis or repeated when feasible.
2.5 Echocardiographic Assessment
Comprehensive transthoracic echocardiography (TTE) was performed at baseline, 3 months, and 6 months using standardized image acquisition protocols across all scanners. All measurements were interpreted offline by two independent readers blinded to clinical data, hemodynamic results, and temporal order of imaging. Discrepancies greater than 10% for volumetric indices or 2% absolute for strain parameters were resolved by consensus.
Left atrial (LA) volume was measured using the biplane area–length method from apical 4- and 2-chamber views at ventricular end-systole and indexed to body surface area (LAVi). LA phasic function was evaluated using speckle-tracking echocardiography following accepted vendor-independent recommendations. Reservoir strain () reflected LA filling during ventricular systole, conduit strain () represented early diastolic emptying, and pump strain () corresponded to active atrial contraction. The zero-strain reference point was defined at end-diastole to maintain internal consistency.
LA stiffness was calculated as the ratio of mitral inflow E/e’ to reservoir strain, providing a non-invasive approximation of atrial mechanical load relative to compliance. Higher values indicated impaired compliance and increased chamber stiffness.
Left ventricular (LV) metrics included LV end-diastolic and end-systolic volumes, LVEF calculated by biplane Simpson’s method, LV global longitudinal strain (GLS), and mitral inflow and annular tissue Doppler velocities. MR severity was classified using an integrative multiparametric assessment encompassing vena contracta width, proximal isovelocity surface area (PISA)-derived effective regurgitant orifice area (EROA), regurgitant volume, pulmonary vein flow, and qualitative jet characteristics. All measurements adhered to the guidelines of the American Society of Echocardiography.
Interobserver and intraobserver reproducibility were assessed in a 20-patient randomly selected subset using intraclass correlation coefficients (ICC).
2.6 Study Endpoints
The primary endpoint was the absolute and relative change in mean LAP from baseline to 6 months following MV repair, reflecting hemodynamic unloading of the left atrium.
A secondary hemodynamic endpoint was the change in peak v-wave pressure across the same interval, representing dynamic alterations in left atrial compliance and mitral inflow resistance.
Secondary structural and functional echocardiographic endpoints included: (1) change in LAVi as a marker of structural remodeling; (2) change in LA phasic strain components (, , ); (3) change in LA stiffness index; (4) the presence of atrial reverse remodeling, defined as reduction in LAVi and/or improvement in reservoir strain relative to baseline; and (5) change in LV function parameters (LVEF, GLS) where relevant.
Clinical endpoints included changes in New York Heart Association (NYHA) functional class, incidence of new-onset atrial fibrillation, and heart failure hospitalization during the 6-month follow-up. All clinical outcomes were adjudicated by physicians blinded to hemodynamic and echocardiographic results.
2.7 Statistical Analysis
Continuous variables were summarized as mean standard deviation or median (interquartile range), based on distribution determined using the Shapiro–Wilk test. Categorical data were expressed as counts and percentages. Longitudinal changes were evaluated using repeated-measures analysis of variance (ANOVA) for normally distributed variables or the Friedman test for nonparametric data. When significant global differences were detected, pairwise comparisons with Bonferroni or Dunn’s correction were applied.
Paired -tests or Wilcoxon signed-rank tests were used to assess within-patient changes between baseline and 6 months. Effect sizes were calculated using Cohen’s for continuous variables.
Logistic regression, with robust standard errors, was used to analyze binary remodeling outcomes. Model discrimination was evaluated using the C-statistic, and calibration was assessed with the Hosmer–Lemeshow test.
Missing data were addressed using multiple imputation by chained equations under a missing-at-random assumption. Ten datasets were imputed and pooled using Rubin’s rules. Cases with missing primary outcome data were excluded from the analysis by design.
Sensitivity analyses included: (1) exclusion of patients who developed postoperative AF; (2) validation-substituted models using PCWP where invasive LAP was unavailable; and (3) subgroup adjustment for repair strategies (leaflet resection, neochordae, sliding plasty).
3 Results
3.1 Cohort Description
A total of 182 consecutive patients were screened, of whom 162 met the study inclusion criteria and completed baseline assessment. Among them, 154 (95.1%) completed all scheduled hemodynamic and echocardiographic follow-up evaluations and formed the final analytic cohort. The mean age was 61.8 10.7 years, and 42.9% were female. All patients had severe degenerative MR, most commonly involving posterior leaflet prolapse (68.2%). Atrial fibrillation (AF) was present in 22.1% of patients (paroxysmal in 84.4%). Hypertension and diabetes mellitus were present in 54.5% and 18.2% of participants, respectively.
Baseline hemodynamic measurements demonstrated an elevated mean LAP of 23.6 5.8 mmHg and peak v-wave pressure of 38.2 9.3 mmHg. Baseline LAVi was 62.4 14.8 mL/m, and LA reservoir strain averaged 20.3 5.1%. Full baseline characteristics are summarized in Table 2.
Baseline Characteristics of the Study Cohort
| Variable | Total (N = 154) | Notes |
| Age (years) | 61.8 10.7 | – |
| Sex (female, %) | 42.9% | – |
| MR etiology | Degenerative | Mostly posterior leaflet |
| AF history | 22.1% | 84.4% paroxysmal |
| Hypertension | 54.5% | – |
| Diabetes mellitus | 18.2% | – |
| Baseline LAP (mmHg) | 23.6 5.8 | – |
| Peak v-wave (mmHg) | 38.2 9.3 | – |
| LAVi (mL/m) | 62.4 14.8 | Marked dilation |
| LA reservoir strain (%) | 20.3 5.1 | Depressed function |
3.2 Primary Outcome: Reduction in Left Atrial Pressure
Mitral valve repair resulted in immediate and sustained improvements in hemodynamic load. Mean LAP decreased significantly from a baseline of 23.6 5.8 mmHg to 15.1 4.7 mmHg immediately postoperatively (p0.001), representing a 36.0% relative reduction. At 6 months, mean LAP further declined to 12.4 3.9 mmHg (p0.001 vs. baseline), amounting to an overall 47.5% reduction from preoperative values.
Peak v-wave pressure exhibited a similar pattern, decreasing from 38.2 9.3 mmHg at baseline to 24.7 7.6 mmHg postoperatively and 21.5 6.4 mmHg at 6 months (p0.001 for trend). The LA compliance index improved from 1.12 0.34 at baseline to 1.48 0.38 at 6 months (p0.001).
A total of 102 patients (66.2%) achieved a reduction in LAP, and 71 (46.1%) achieved a reduction. Hemodynamic trends are summarized in Table 3.
Hemodynamic Changes Following Mitral Valve Repair
| Variable | Baseline | Post-op | 6 months | (Baseline 6 months) |
| Mean LAP (mmHg) | 23.6 | 15.1 | 12.4 | 11.2 |
| Peak v-wave (mmHg) | 38.2 | 24.7 | 21.5 | 16.7 |
| LA compliance index | 1.12 | 1.27 | 1.48 | +0.36 |
3.3 Secondary Outcomes: Structural Remodeling
Significant structural reverse remodeling of the left atrium was observed over time. LAVi decreased from 62.4 14.8 mL/m at baseline to 54.2 13.1 mL/m at 3 months (p0.001), and further to 48.7 12.6 mL/m at 6 months (p0.001 vs. both time points). The mean relative reduction in LAVi at 6 months was 21.9%.
Maximum LA diameter decreased from 48.3 6.9 mm to 44.5 6.1 mm at 6 months (p0.001), representing an 8.0% reduction. Based on prespecified criteria, 94 patients (61.0%) met the definition of structural reverse remodeling. Results are summarized in Table 4.
Left Atrial Structural Remodeling Over Time
| Parameter | Baseline | 3 months | 6 months | % Change |
| LAVi (mL/m) | 62.4 | 54.2 | 48.7 | 21.9% |
| Max LA diameter (mm) | 48.3 | 46.2 | 44.5 | 8.0% |
3.4 Secondary Outcomes: Functional Remodeling
LA functional indices demonstrated pronounced improvement following reduction in volume and pressure overload. Reservoir strain increased from 20.3 5.1% at baseline to 26.8 6.0% at 6 months (p0.001), reflecting a mean relative improvement of 32.0%. Conduit strain improved from 12.1 4.2% to 16.0 4.8% (p0.001), and pump strain rose from 10.4 3.5% to 13.8 3.9% (p0.001).
LA stiffness index improved significantly, decreasing from 0.54 0.18 to 0.38 0.14 (p0.001). A total of 88 patients (57.1%) met the definition of functional reverse remodeling.
Left Atrial Functional Remodeling Following MV Repair
| Metric | Baseline | 6 months | p-value | |
| LA reservoir strain (%) | 20.3 | 26.8 | +6.5 | 0.001 |
| LA conduit strain (%) | 12.1 | 16.0 | +3.9 | 0.001 |
| LA pump strain (%) | 10.4 | 13.8 | +3.4 | 0.001 |
| LA stiffness index | 0.54 | 0.38 | 0.16 | 0.001 |
3.5 Predictors of Reverse Remodeling
In multivariable regression, higher baseline LAP (, 95% CI: 0.14–0.46, p=0.001), larger baseline LAVi (, 95% CI: 0.10–0.44, p=0.003), and lower baseline reservoir strain (, 95% CI: 0.32 to 0.04, p=0.014) were independently associated with greater LAVi reduction at 6 months. Age, sex, and baseline LV function were not predictive of remodeling outcomes.
Predictors of Left Atrial Reverse Remodeling
| Variable | Coefficient | 95% CI | p-value |
| Baseline LAP (mmHg) | 0.31 | 0.14–0.46 | 0.001 |
| Baseline LAVi (mL/m) | 0.27 | 0.10–0.44 | 0.003 |
| Baseline LA reservoir strain (%) | 0.18 | 0.32–0.04 | 0.014 |
| Age (years) | 0.06 | 0.05–0.17 | NS |
3.6 Clinical Outcomes
At 6 months, 118 patients (76.6%) demonstrated improvement in NYHA class, with 62 (40.3%) improving by at least two classes. New-onset atrial fibrillation occurred in 11 patients (7.1%), and heart failure hospitalization occurred in 9 patients (5.8%). No deaths were recorded during the follow-up period.
Clinical Outcomes at 6-Month Follow-up
| Outcome | 6 months | Notes |
| NYHA class improvement | 76.6% | 40.3% improved classes |
| New-onset atrial fibrillation | 7.1% | – |
| Heart failure hospitalization | 5.8% | – |
4 Discussion
4.1 Principal Findings
In this prospective cohort study of patients undergoing surgical mitral valve repair for severe degenerative mitral regurgitation, we observed substantial and consistent improvements in left atrial (LA) hemodynamics, structure, and function over a 6-month follow-up period. First, mean left atrial pressure (LAP) declined immediately following surgical correction and continued to decrease at 6 months, resulting in an overall reduction of nearly 50% from baseline. This hemodynamic improvement was accompanied by a marked reduction in peak v-wave pressure and a progressive increase in LA compliance, demonstrating sustained unloading of the left atrium.
Second, structural reverse remodeling occurred in the majority of patients, as reflected by reductions in indexed LA volume and maximal LA diameter. Nearly two-thirds of the cohort met the prespecified definition of structural reverse remodeling. Third, functional recovery was robust, with significant improvements in reservoir, conduit, and pump strain components as well as a decrease in LA stiffness index, suggesting that both passive and active phases of atrial function were restored.
Finally, baseline LAP, LAVi, and LA strain emerged as independent predictors of subsequent remodeling. These findings collectively support a strong interplay between hemodynamic unloading and subsequent anatomic and functional recovery of the left atrium. Together, they highlight the capacity of the atrium for meaningful reverse remodeling following relief of chronic volume overload.
4.2 Mechanistic Interpretation
The pathophysiologic basis for the observed changes is consistent with the known consequences of chronic mitral regurgitation. Severe degenerative MR imposes a persistent volume load on the left atrium, resulting in chamber dilation, increased wall stress, and eventual impairment of compliance. Over time, these changes manifest as elevated LAP, reduced reservoir strain, and increased atrial stiffness. Correction of MR removes the primary driver of these abnormalities, allowing for partial restoration of atrial geometry and function.
The substantial reductions in LAP and v-wave pressure observed in our cohort underscore the central role of hemodynamic unloading in promoting atrial recovery. Lower atrial filling pressures reduce wall tension and facilitate normalization of atrial mechanics. Improvements in strain likely reflect both the restoration of passive reservoir function and enhanced contractile performance of the atrial myocardium.
However, the degree of remodeling varied across individuals, suggesting biological limits to reversibility. Chronic exposure to elevated pressures can lead to atrial fibrosis, an irreversible structural alteration that impairs mechanical deformation and electrical conduction. Patients with more advanced fibrosis may therefore exhibit attenuated responses. Although our study did not directly quantify atrial fibrosis, the heterogeneity of remodeling and the predictive value of baseline strain support this mechanism. Future studies incorporating cardiac magnetic resonance or advanced echocardiographic fibrosis markers may help clarify the extent to which structural myocardial disease limits LA recovery.
4.3 Comparison With Previous Studies
Our findings align closely with prior research demonstrating LA reverse remodeling following surgical or transcatheter correction of MR. Antonini-Canterin and colleagues (2008) reported early reductions in LA volume after MV repair, whereas Stassen et al. (2022) extended these observations by showing that long-term reductions in LAVi are associated with improved clinical outcomes. Similarly, work by Ledwoch et al. (2019) and Pio et al. (2024) highlighted improvements in LA strain following percutaneous repair.
Our study advances the current literature in several important ways. First, invasive measurement of LAP is rarely performed in contemporary cohorts, yet it provides a direct physiologic correlate to atrial remodeling. By integrating invasive hemodynamics with advanced echocardiographic functional indices, we were able to characterize the relationship between pressure unloading and strain recovery more precisely than prior work relying solely on noninvasive surrogate markers. Second, the prospective design and standardized imaging protocol minimize measurement variability and strengthen causal interpretation. Third, the identification of baseline hemodynamic and structural parameters as predictors of remodeling provides insights into patient selection and risk stratification that have not been consistently demonstrated across earlier studies.
4.4 Clinical Implications
Our findings have several important implications for the clinical management of degenerative MR. First, the strong association between early hemodynamic improvement and subsequent structural and functional recovery suggests that LAP reduction may serve as an early marker of successful atrial remodeling. Clinicians may consider incorporating LAP or PCWP assessment in selected cases, particularly when evaluating postoperative recovery or the adequacy of repair.
Second, improvements in LA strain following MV repair highlight its potential role as a sensitive follow-up marker. Because strain reflects both reservoir and contractile function, its recovery may signal favorable atrial mechanics long before reductions in LA volume are observed. Serial strain assessment could inform prognosis, refine clinical follow-up schedules, and potentially identify patients at risk of persistent dysfunction.
Third, the presence of structural and functional remodeling has implications for the timing of surgery. Patients with severe MR who remain asymptomatic may still benefit from earlier intervention to prevent irreversible atrial remodeling, including fibrosis. Our findings reinforce current guideline recommendations advocating timely surgical repair in appropriate candidates.
Finally, the relatively low incidence of new-onset atrial fibrillation and heart failure hospitalization in our cohort underscores the potential role of MV repair in mitigating downstream clinical complications. Given the established association between LA enlargement, stiffness, and arrhythmogenesis, successful reverse remodeling may reduce long-term AF risk, although longer follow-up is needed.
4.5 Strengths and Limitations
This study has several notable strengths. The prospective design, use of invasive hemodynamic assessment, and comprehensive evaluation of LA structure and function provide a robust dataset for evaluating atrial remodeling after MV repair. Standardized imaging protocols, blinded image analysis, and reproducibility assessment further enhance methodological rigor.
The study also has limitations. It was conducted at a single high-volume center, potentially limiting generalizability. The follow-up period was limited to 6 months, whereas atrial remodeling may continue over 12–24 months. We did not assess LA fibrosis directly, limiting mechanistic interpretation of heterogeneous remodeling patterns. Finally, although multiple sensitivity analyses were performed, residual confounding cannot be fully excluded.
Despite these limitations, our findings add meaningfully to the growing body of evidence supporting the capacity of the left atrium to recover after timely correction of degenerative MR.
5 Conclusion
Surgical repair of severe degenerative mitral regurgitation resulted in substantial and sustained improvements in left atrial hemodynamics, structure, and function. Mean LAP and v-wave pressure decreased markedly, while atrial compliance and phasic strain components improved, indicating meaningful reversal of atrial remodeling within six months of surgery. Structural indices such as LAVi also declined significantly, and more than half of patients met criteria for reverse remodeling. Baseline LAP, LAVi, and reservoir strain were important predictors of recovery, underscoring the interplay between hemodynamic unloading and atrial adaptation. These findings support timely intervention for degenerative MR and highlight the value of comprehensive atrial assessment—including strain imaging—for postoperative monitoring and prognostic evaluation.
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