Severe Degenerative Mitral Regurgitation Research Articles

Prevalence, characteristics, and long-term outcomes of patients with mitral annular disjunction undergoing surgery for degenerative mitral regurgitation

Abstract Background Mitral valve prolapse (MVP) is associated with progressive mitral regurgitation (MR) requiring surgical repair. A subset of patients with MVP may also suffer from malignant ventricular arrhythmias (VAs), especially in the presence of mitral annular disjunction (MAD). Purpose To assess the prevalence, associated characteristics, and long-term outcomes of patients with MVP with and without MAD undergoing mitral valve surgery for degenerative MR. Methods Patients with MVP and moderate-to-severe or severe degenerative MR undergoing mitral valve surgery between 2010-2022 at a university hospital in Sweden were included. MAD length was measured on echocardiograms at end-systole from the insertion of the posterior leaflet on the detached mitral annulus to the border of the bulging left ventricle. Patient demographics and clinical outcomes were collected from medical records. The primary endpoint consisted of VAs, defined as sustained- or non-sustained ventricular tachycardia or high burden of premature ventricular complexes causing hospitalizations or ablation or identified at Holter monitoring. Other endpoints included sudden cardiac death, all-cause mortality, new onset postoperative atrial fibrillation, stroke, mitral valve reoperation, endocarditis, new or worsened heart failure, myocardial infarction and implantation of permanent pacemaker or cardiac defibrillator. Results Of 599 patients undergoing mitral valve surgery, 96 (16%) had preoperative MAD, with a median (Q1, Q3) MAD length of 8.0 (5.0-10.0) mm. Compared with patients without MAD, patients with MAD were younger (55 vs 63 years), more likely to be female (31% vs 17%), to have diffuse myxomatous valve disease (66% vs 25%) and bileaflet prolapse (57% vs 17%). Most patients underwent mitral valve repair (84% vs 80%). No patient had residual MAD after surgical repair. At a mean follow up time of 5.8 ± 3.5 years after mitral valve repair, VAs were more common in patients with pre-operative MAD (10% vs 2% (adjusted HR 4.52, 95% CI 1.57-13.0)) (Figure 1). There were no significant differences in the risks of other clinical outcomes. Conclusions MAD was associated with almost a 5-fold increased long-term risk of VAs after mitral valve repair despite successful anatomical correction of MAD. These findings highlight the importance of increased awareness of VAs in patients with MAD also after mitral valve surgery.

Identification of left ventricular flow features in healthy and pathological conditions

Abstract Background In the presence of mitral valve diseases or following surgical interventions, the hemodynamics in the left ventricle (LV) are significantly altered [1]. These maladaptive intraventricular hemodynamic alterations can stimulate a cascade of events leading to progressive adverse LV remodeling and eventual heart failure [2]. Qualitative and quantitative evaluation of LV flow features may provide a potential for sensitive risk stratification of clinical cardiac function [3]. Purpose The purpose of this study is to identifying LV flow features using in vitro experiments under both normal and pathological conditions, including mitral regurgitation (MR), mitral valve replacement with bioprosthetic/mechanical valve, and transcatheter mitral valve edge-to-edge repair (TEER). Methods We utilized a biohybrid approach to construct the in vitro experimental platform, where the native mitral valve (including chordae tendineae and papillary muscles) and aortic valve from porcine were combined with a 3D-printed silicon LV (figure 1). To ensure comparability across different conditions, we maintained consistency by utilizing the same native valve and 3D-printed LV. For pathological conditions, we cut the chordae tendineae in A2 zone to induce the severe degenerative MR, and TEER was performed on this prolapsed valve by placing two clips in A2-P2 zone. Then, the anterior leaflet of valve was cut, and a bioprosthetic valve and mechanical valve were sutured to mitral annulus to simulate surgical valve replacement, respectively. Left ventricular flow fields were measured using four-dimensional particle image velocimetry (4D-PIV) technique, with vector interval of 0.9 mm in all the spatial directions and temporal resolution of 10 ms. Results Significant differences in mean flow field were observed among healthy and pathological conditions (figure 2). Firstly, the vortex orientation was clockwise in healthy, MR, bioprosthetic valve replacement, and TEER conditions, which could accompany the redirection of blood flows towards the aortic valve. However, the replacement with a mechanical valve resulted in an alteration in vortex orientation from clockwise to counterclockwise. Secondly, the position of the center of the vortex changed in pathological conditions, with the center of the vortex closest to the apex and the left ventricle outflow tract in the healthy condition. Thirdly, the maximum Reynolds shear stress (RSS), which may be responsible for thrombus formation, significantly increased after TEER procedure and bioprosthetic valve replacement. Conclusions This study demonstrates significant changes in LV hemodynamics across different conditions. The flow features, including vortex orientations, vortex positions and the RSS, may potentially become crucial considerations for the optimization of artificial valves and mitral valve repair devices.Figure 1 Figure 2

Impact of surgical technique on postoperative ventricular arrhythmias in arrhythmic mitral valve prolapse

Abstract Background Mitral valve prolapse (MVP) is associated with progressive mitral regurgitation (MR) requiring surgical correction. A subset of patients with MVP may also constitute an "arrhythmic" phenotype suffering from malignant ventricular arrhythmias (VAs). Purpose To assess the impact of surgical technique for correction of degenerative MR including repair using artificial chords, repair with resection and mitral valve replacement (MVR) on longitudinal risk of VAs in patients with arrhythmic MVP. Methods Patients who had undergone mitral valve surgery for MVP with moderate to severe degenerative MR between 2010-2022 at a university hospital in Sweden were retrospectively included. Patients with ischemic heart disease, primary cardiomyopathy, channelopathy, or endocarditis were excluded. To examine changes in VAs (defined as sustained- or non-sustained ventricular tachycardias) as assessed by continuous Holter monitoring before and after surgery, generalized estimating equation (GEE) models were performed to account for the correlations between repeated monitoring in each patient and for differences in the time of measurement. Results Of 599 patients undergoing mitral valve surgery, 423 (71%) underwent repair using artificial chords, 62 (10%) repair with resection and 114 (19%) MVR. For those presenting with symptoms such as palpitations, presyncope, and/or syncope, Holter monitoring was conducted before (n=171; 29%) and/or after mitral valve surgery (n=184; 31%) (Figure 1). The distribution of VAs before and after surgery, stratified by surgical technique, is illustrated in Figure 2. In GEE models, repair using artificial chords was associated with increased postoperative VAs compared with the other surgical techniques (OR 2.14; 95% CI 1.19-3.83; p=0.01), repair with resection with reduced postoperative VAs compared with the other surgical techniques (OR 0.15; 95% CI 0.04-0.61; p=0.01), and no change in postoperative VAs was observed for MVR compared with the other surgical techniques (OR 0.724; 95% CI 0.39-1.35; p=0.31). The results remained similar after adjustment for age, sex, myxomatous disease/fibroelastic deficiency or bileaflet prolapse. Conclusion In patients with symptoms of palpitations, presyncope and/or syncope before or after mitral valve surgery, repair using artificial chords was associated with an increased risk of postoperative VAs. Prospective studies including continuous monitoring before and after surgery are needed to confirm these findings.

The prevalence, etiologies and clinical consequences of tricuspid regurgitation associated with severe degenerative mitral regurgitation.

The prevalence, the etiologies and the clinical features of tricuspid regurgitation (TR) in the context of concomitant degenerative mitral valve (MV) disease are poorly defined. This paper aims to assess the prevalence, determinants and clinical consequences of TR in severe degenerative mitral regurgitation (DMR). Clinical and echocardiographic characteristics were collected among patients with severe DMR. 884 patients were included in our study, 31% with > moderate TR. Tricuspid valve prolapse (TVP) was the most common etiology (487 patients, 55%), followed by atrial functional TR (AFTR, 172 patients, 19%) and ventricular functional TR (VFTR, 42 patients, 5%), while TR etiology was mixed in 183 (21%) patients. Patients with TVP were younger, had better clinical presentation, had few comorbidities, and had less hemodynamically relevant TR. VFTR patients were characterized by older age, worst clinical presentation and both highest comorbidity rate and prevalence of >mild TR. AFTR group showed an intermediate profile of clinical presentation and comorbidities and the largest tricuspid annulus (TA) diameter.MV surgery was performed in 785 (88%) patients; 132 (15%) underwent simultaneous TV intervention, more often AFTR patients (32%). TA dilatation (OR 3.68, CI 2.05-6.62, p <0.001) and >mild TR (OR 9.30, CI 5.10-16.95, p<0.001) were independently associated with TV intervention. In patients with severe DMR, TR presents with different etiologies, clinical features and echocardiographic phenotypes that require a comprehensive assessment at the time of DMR surgery to ensure the best management for these patients.

Indexing left ventricular end-systolic dimension to body size: Association with mortality in patients with degenerative mitral regurgitation.

In patients with degenerative mitral regurgitation (DMR), left ventricular (LV) dysfunction is associated with increased risk of heart failure and excess mortality. LV end-systolic diameter (LVESD) is an established trigger for intervention, yet recommended LVESD thresholds apply poorly to patients with small body size. Whether LV normalization to body surface area (BSA) may be used as a trigger for DMR correction is unknown. We examined the link between LVESD index (LVESDi) and outcome in DMR to identify appropriate thresholds for excess mortality. This study focuses on 2753 consecutive patients with DMR due to flail leaflets diagnosed in tertiary centres from Europe and the United States, with prospective echocardiographic measurement of LVESD and BSA and long-term follow-up. The primary endpoint was mortality after diagnosis under conservative management. Secondary endpoints were mortality under conservative and surgical management and postoperative mortality of patients who underwent surgery. The optimal LVESDi cut-off for mortality prediction was 20 mm/m2. Irrespective of management type, 10-year survival was lower with LVESDi ≥20 mm/m2 than with LVESDi <20 mm/m2 (both p < 0.001). After covariate adjustment, LVESDi ≥20 mm/m2 was independently predictive of mortality under conservative management (adjusted hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.15-1.75), and with conservative and surgical management (adjusted HR 1.34, 95% CI 1.17-1.54). LVESDi remained associated with poorer postoperative outcome in patients who underwent intervention. LVESDi showed higher incremental predictive value over the baseline model compared to LVESD. The association between LVESDi ≥20 mm/m2 and outcome was consistent in subgroups of patients with DMR. In severe DMR due to flail leaflets, LVESDi is a marker of risk additive and incremental to LVESD. Its use in clinical practice should lead to earlier referral to mitral valve surgery and improved long-term outcome.

Survival loss linked to guideline-based indications for degenerative mitral regurgitation surgery.

Operating on patients with severe degenerative mitral regurgitation (DMR) is based on ACC/AHA or ESC/EACTS-guidelines. Doubts persist on best surgical indications and their potential association with postoperative survival loss. We sought to investigate whether guideline-based indications lead to late postoperative survival loss in DMR-patients. : We analyzed outcome of 2833 patients from the MIDA-registry undergoing surgical correction of DMR. Patients were stratified by surgical indications: Class-I-trigger (symptoms, left ventricular end-systolic diameter≥40mm, or left ventricular ejection fraction<60%, n=1677), isolated-Class-IIa-trigger (atrial fibrillation [AF], pulmonary hypertension [PH], or left atrial diameter≥55mm, n=568), or no-trigger (n=588). Postoperative survival was compared after matching for clinical differences. Restricted-mean-survival time (RMST) was analyzed. During a median 8.5-year follow-up, 603 deaths occurred. Long-term postoperative survival was lower with Class-I-trigger than in Class-IIa-trigger and no-trigger (71.4±1.9%, 84.3±2.3%, 88.9±1.9% at 10 years, p<0.001). Having at least one Class-I-criterion led to excess mortality (p<0.001), while several Class-I-criteria conferred additional death-risk (HR:1.53, 95%CI:1.42-1.66). Isolated-Class-IIa-triggers conferred an excess mortality risk versus those without (HR:1.46, 95%CI:1.00-2.13, p=0.05). Among these patients, isolated-PH led to decreased postoperative-survival versus those without (83.7%±2.8% vs. 89.3%±1.6%, p=0.011), with the same pattern observed for AF (81.8%±5.0% vs. 88.3%±1.5%, p=0.023). According to RMST-analysis, compare to those operated on without triggers, operating on Class-I-trigger patients led to 9.4-month survival-loss (p<0.001) and operating on isolated-Class-IIa-trigger patients displayed 4.9-month survival loss (p=0.001) after 10-years. : Waiting for the onset of Class-I or isolated-Class-IIa-triggers before operating on DMR patients is associated with postoperative survival loss. These data encourage an early surgical-strategy.

Island Flap Rotation Technique as a Novel Repair Surgery Method for Severe Degenerative Mitral Valve Regurgitation

Background: The current study was done to assess the efficacy and safety of the island flap rotation technique as a novel method for severe mitral valve regurgitation. Methods: Twenty-three patients were selected to undergo mitral valve repair with the island flap rotational technique. It takes the principle of doing quadrangular resection of the P2 leaflet and flipping the dissected area so that the ruptured primary chordae are replaced with the secondary or tertiary chordae. Transesophageal echocardiography parameters were evaluated before surgery and 1 week after surgery, just prior to discharge. Results: The procedure was done successfully with 100% mitral regurgitation reduction to ≤1+ along with significantly reduced left ventricular end-diastolic diameter (p = 0.001) and left atrial dimension (p = 0.000). The left ventricular ejection fraction was significantly reduced after the procedure (p = 0.000). Older age significantly affects the presence of residual mitral regurgitation (p = 0.02). No thromboembolic adverse events and mortality were observed during the 3-month follow-up. Conclusions: The use of island flap rotation technique as a novel method for severe mitral regurgitation with P2 lesions has been proven to be effective and safe with preserving the valve tissue.

Degenerative mitral regurgitation due to flail leaflet: sex-related differences in presentation, management, and outcomes.

Presentation, outcome, and management of females with degenerative mitral regurgitation (DMR) are undefined. We analysed sex-specific baseline clinical and echocardiographic characteristics at referral for DMR due to flail leaflets and subsequent management and outcomes. In the Mitral Regurgitation International Database (MIDA) international registry, females were compared with males regarding presentation at referral, management, and outcome (survival/heart failure), under medical treatment, post-operatively, and encompassing all follow-up. At referral, females (n = 650) vs. males (n = 1660) were older with more severe symptoms and higher MIDA score. Smaller cavity diameters belied higher cardiac dimension indexed to body surface area. Under conservative management, excess mortality vs. expected was observed in males [standardized mortality ratio (SMR) 1.45 (1.27-1.65), P < .001] but was higher in females [SMR 2.00 (1.67-2.38), P < .001]. Female sex was independently associated with mortality [adjusted hazard ratio (HR) 1.29 (1.04-1.61), P = .02], cardiovascular mortality [adjusted HR 1.58 (1.14-2.18), P = .007], and heart failure [adjusted HR 1.36 (1.02-1.81), P = .04] under medical management. Females vs. males were less offered surgical correction (72% vs. 80%, P < .001); however, surgical outcome, adjusted for more severe presentation in females, was similar (P ≥ .09). Ultimately, overall outcome throughout follow-up was worse in females who displayed persistent excess mortality vs. expected [SMR 1.31 (1.16-1.47), P < .001], whereas males enjoyed normal life expectancy restoration [SMR 0.92 (0.85-0.99), P = .036]. Females with severe DMR were referred to tertiary centers at a more advanced stage, incurred higher mortality and morbidity under conservative management, and were offered surgery less and later after referral. Ultimately, these sex-related differences yielded persistent excess mortality despite surgery in females with DMR, while males enjoyed restoration of life expectancy, warranting imperative re-evaluation of sex-specific DMR management.

Sex-Specific Prognosis of Left Ventricular Size and Function Following Repair of Degenerative Mitral Regurgitation

BackgroundPrior studies have demonstrated worse long-term outcomes for women after surgery for severe mitral regurgitation (MR). The current Class I indications for surgery for severe degenerative MR use cutoffs of left ventricular end-systolic dimension (LVESD) and left ventricular ejection fraction (EF) that do not account for known sex-related differences. ObjectivesThe primary objective of this study was to assess long-term mortality following mitral valve repair in women compared with men on the basis of preoperative left ventricular systolic dimensions and EF. MethodsConsecutive patients who underwent isolated mitral valve repair for degenerative MR at a single institution between 1994 and 2016 were screened. Adjusted HRs for all-cause mortality were compared according to baseline LVESD, LVESD indexed to body surface area (LVESDi), and EF for men and women. ResultsAmong 4,589 patients, 1,825 were women (40%), and after a median follow-up period of 7.2 years, 344 patients (7.5%) had died. The risk for mortality for women increased from the baseline hazard at an LVESD of 3.6 cm, whereas an inflection point for increased risk with LVESD was not evident in men. Regarding LVESDi, the risk for women increased at 1.8 cm/m2 compared with 2.1 cm/m2 in men. For EF, women and men had a similar inflection point (58%); however, mortality was higher for women as EF decreased. ConclusionsAfter mitral valve repair, women have a higher risk for all-cause mortality at lower LVESD and LVESDi and higher EF. These results support consideration of sex-specific thresholds for LVESDi in surgical decision making for patients with severe MR.

Eccentric remodeling in patients undergoing mitral valve repair due to severe degenerative mitral regurgitation: impact of relative wall thickness on clinical outcomes

Abstract Background Left ventricular (LV) volume overload in mitral regurgitation (MR) leads to a progressive increase in LV mass. Eccentric hypertrophy is defined as the relative wall thickness (RWT) &amp;lt;0.43, and LV hypertrophy is a frequently observed LV remodeling phenotype in patients with severe MR. However, the prognostic impacts of RWT in these patient groups are not well known. We tested the relationship between RWT and clinical outcomes in severe MR patients undergoing MV repair (MVR). Methods A total of 979 consecutive adult patients with severe degenerative MR and eccentric hypertrophy (55 ± 13 years, 616 males) who underwent MVR were retrospectively analyzed. The study population was stratified by the median RWT value (RWT=0.34) on baseline echocardiography [the lesser RWT group (RWT&amp;lt; 0.34 (n=651)) and the greater RWT group (RWT ≥0.34 (n = 328)). Results The patients in the lesser RWT group were younger (54±13 vs. 57±13, p&amp;lt;0.001) and had a significantly higher prevalence of hypertension and diabetic mellitus than those in the greater RWT group. The greater RWT group had significantly lower indexed LV systolic dimension, thicker ventricular walls, and higher LV ejection fraction as compared with those in the lesser RWT group. In Kaplan-Meier analysis, the greater RWT group had a significantly higher incidence of all-cause death (6.4% vs. 2.3%; log-rank p&amp;lt;0.001) and cardiac death (3.0% vs. 0.9%; log-rank p = 0.01) at five years after MVR than in the low RWT group. RWT≥0.34 was independently associated with higher all-cause and cardiac mortality in the multivariate Cox regression analysis. In subgroup analysis, RWT≥0.34 was associated with worse outcomes in men (P &amp;lt;0.001) but not in women (P = 0.23). Moreover, hypertensive patients in the greater RWT group showed the worst outcomes as compared with the three other groups. Conclusions We concluded that excessive ventricular hypertrophy, manifested as an increased relative wall thickness, is associated with a significantly increased risk of postoperative mortalities after mitral valve repair in patients with severe degenerative MR and eccentric hypertrophy. We also found that eccentric remodeling patterns and clinical outcomes differ according to sex and the presence of hypertension.

Left Atrial Stiffness Index as a Predictor of Effort Intolerance and Hemodynamics Evaluated by Invasive Exercise Stress Testing in Degenerative Mitral Regurgitation

In patients with degenerative mitral regurgitation (DMR), peak oxygen consumption is the significant prognostic factor, and exercise intolerance has been considered a trigger for surgical intervention. The significant mitral regurgitation (MR) induces left atrial (LA) remodeling, but the significance of LA stiffness calculated by the ratio of E/e' to LA reservoir strain in degenerative MR has not been elucidated. A total of 30 patients with asymptomatic or minimally symptomatic grade ≥III+DMR underwent the cardiopulmonary exercising test simultaneously with invasive hemodynamic assessment. LA stiffness index significantly correlated with exercise hemodynamic deterioration, including pulmonary arterial wedge pressure (r=0.71, p <0.01), systolic pulmonary arterial pressure at peak exercise (r=0.73, p <0.01), and pulmonary circulatory reserve (mean pulmonary arterial pressure/cardiac output slope, r=0.45, p=0.012). Multiple linear regression analysis revealed that the higher LA stiffness index was significantly associated with decreased percent predicted peak oxygen consumption (per 0.1 increase, β -4.0, 95% confidence interval -6.9 to -1.3, p <0.01) independently of MR deterioration during exercise. In conclusion, increased LA stiffness was associated with exercise intolerance through hemodynamic deterioration during exercise in patients with asymptomatic or minimally symptomatic severe DMR.

Neochordae implantation versus leaflet resection in mitral valve posterior leaflet prolapse and dilated left ventricle: a propensity score matching comparison with long-term follow-up.

Uncorrected severe mitral regurgitation (MR) due to posterior prolapse leads to left ventricular dilatation. At this stage, mitral valve repair becomes mandatory to avoid permanent myocardial injury. However, which technique among neochoardae implantation and leaflet resection provides the best results in this scenario remains unknown. We selected 332 patients with left ventricular dilatation and severe degenerative MR due to posterior leaflet (PL) prolapse who underwent neochoardae implantation (85 patients) or PL resection (247 patients) at our institution between 2008 and 2020. A propensity score matching analysis was carried on to decrease the differences at baseline. Matching yielded 85 neochordae implantations and 85 PL resections. At 10 years, freedom from cardiac death and freedom from mitral valve reoperation were 92.6 ± 6.1% vs 97.8 ± 2.1% and 97.7 ± 2.2% vs 95 ± 3% in the neochordae group and in the PL resection group, respectively. The MR ≥2+ recurrence rate was 23.9 ± 10% in the neochordae group and 20.8 ± 5.8% in the PL resection group (P = 0.834) at 10 years. At the last follow-up, the neochordae group showed a higher reduction of left ventricular end-diastolic diameter (44 vs 48 mm; P = 0.001) and a better ejection fraction (60% vs 55%; P < 0.001) compared to PL resection group. In this subgroup of patients, both neochordae implantation and leaflet resection provide excellent durability of the repair in the long term. Neochordae implantation might have a better effect on dilated left ventricle.

Secondary leaflet tethering in patients with severe degenerative mitral regurgitation and its association with the severity of mitral regurgitation.

The purpose of the study was to determine the association between vena contracta area (VCA) and secondary leaflet tethering among mitral valve prolapse (MVP) patients, and thus to further identify and characterize an MVP with pathological leaflet tethering (MVPt+) phenotype. We prospectively evaluated 94 consecutive MVP patients with significant mitral regurgitation (MR) and 21 healthy controls. MVPt+ group was defined as tenting volume index (TVi)>.7mL/m2 . The three-dimensional (3D) geometry of mitral valve apparatus and VCA was measured with dedicated quantification software. Of the 94 patients with MVP and significant MR, 31 patients showed a TVi>.7mL/m2 and entered the MVP with leaflet tethering (MVPt+) group. In stepwise multivariate analysis, only prolapse volume index and TVi were independently associated with 3D VCA. 3D VCA, annular area index, and plasma levels of NT-proBNP were independently correlated with the severity of leaflet tethering. ROC curve revealed that a 3D VCA ≥ .55 cm2 is the optimal cutoff point to predict MVPt+ phenotype. Secondary leaflet tethering is a significant mechanism behind severe degenerative MR, resulting in an MVPt+ phenotype featuring more advanced morphological and hemodynamical characteristics.

Clinical and Prognostic Implications of Cardiopulmonary Exercise Stress Echocardiography in Asymptomatic Degenerative Mitral Regurgitation

The current guidelines recommend intervention in severe degenerative mitral regurgitation (MR) in symptomatic patients or asymptomatic patients with left ventricular dilatation or dysfunction. The insidious onset of symptoms may mean that patients do not report their symptoms. The role of systematic exercise testing for symptoms in MR is not clearly defined. A total of 97 patients with moderate to severe asymptomatic MR underwent exercise echocardiography combined with cardiopulmonary exercise testing. The predictors of exercise-induced dyspnea, symptom-free survival, and mitral valve intervention were identified. A total of 18 patients (19%) developed limiting dyspnea on exercise. Spontaneous symptom-free survival at 24months was significantly higher in those without exercise-induced symptoms than those with exercise-induced symptoms, p <0.0001. The only independent predictors of spontaneous symptoms at 2years were effective regurgitant orifice area (odds ratio 27.45, 95% confidence interval [CI] 1.43 to 528.40, p=0.03) and exercise-induced symptoms (odds ratio 11.56, 95% CI 1.71 to 78.09, p=0.01). The only independent predictor of surgery was indexed left ventricular systolic volumes (odds ratio 1.17, 95% CI 1.04 to 1.30, p=0.006). Where only the patients who underwent surgery due to symptoms were included, the only independent predictor was exercise-induced symptoms (odds ratio 13.94, 95% CI 1.39 to 140.27, p=0.025). In conclusion, in patients with primary asymptomatic degenerative MR, 1/5 develop revealed symptoms during exercise. This predicts a subsequent development of spontaneous symptoms and mitral valve intervention due to symptoms.

TAPSE/PAPS ratio as a predictor of hospital staying in patients affected by severe degenerative mitral regurgitation undergoing mitral valve surgery

Abstract Funding Acknowledgements Type of funding sources: None. Background Chronic severe degenerative mitral regurgitation (DMR) is a progressive disease with a negative impact on prognosis and surgical repair or replacement represents the standard of care. Recently, the coupling between right ventricular (RV) function and the pulmonary circulation (Pc) emerged as a prognostic index in patients undergoing transcatheter edge-to-edge mitral repair. However, the relationship between pulmonary circulatory right ventricular uncoupling and clinical outcomes in patients undergoing surgery for DMR has poorly been investigated. Purpose In a cohort of patients affected by DMR undergoing mitral valve surgery (repair or replacement), we investigated the association between the degree of RV-to-Pc uncoupling, assessed by the ratio between tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PAPS), and the time of hospitalization. Methods 389 consecutive patients affected by DMR who underwent mitral surgery (repair or replacement) were retrospectively enrolled. In the pre-operatory phase, all patients underwent a transthoracic echocardiography. The degree of RV-to-PC uncoupling was defined by TAPSE/PASP ratio with a cut-off of 0.4 mm/mmHg and was correlated with the time of hospitalization expressed in days. Results A total of 389 eligible patients (mean age 52±14 y, 65% male, 85% in sinus rhythm) who were admitted for mitral valve surgery at San Raffaele hospital (85% repair, 15% replacement) for hemodynamically significant DMR were retrospectively enrolled from January 2019 to June 2022. Mean hospital stay was 11±8 days. At baseline, only 28% of the cohort exhibited normal left ventricular (LV) and left atrial (LA) size and function, with the majority of the cohort exhibiting increased LA dimension (mean LAVi 49±10 ml/m2). RV to PC coupling was measured before surgery (mean TAPSE/PAPS: 0.8±0.2 mm/mmHg) and only 15% of the cohort had a TAPSE/PAPS≤0.4 mm/mmHg. Interestingly, patients with lower TAPSE/PAPS ratio had longer hospitalization (TAPSE/PAPS≤0.4 mm/mmHg: 15±8.2 days vs TAPSE/PAPS &amp;gt;0.4 mm/mmHg: 11±7.5 days; p = 0.04) and an inverse relationship was found between TAPSE/PAPS values at admission and the length of hospitalization (r=0.4, CI 95% 0.21–0.57; p&amp;lt;0.001; Figure 1). Conclusions In DMR, a strong association was noted between TAPSE/PAPS ratio and length of hospitalization in patients undergoing mitral valve surgery. These data, although preliminary, underline the impact of RV dysfunction and PC uncoupling on clinical outcomes also in the short-term evolution after surgery.

Left atrial function as a determinant of symptoms in patients with severe degenerative mitral regurgitation

Abstract Funding Acknowledgements Type of funding sources: None. Background Understanding the pathophisiology of symptoms onset in degenerative mitral regurgitation may be helpful in the management of asymptomatic patients. Left atrium (LA) is far from simply being a passive connection chamber between mitral valve and pulmonary circulation, and the role of left atrial function as a predictor of symptoms onset has not yet been evaluated. The increase in atrial pressure that causes elevation of pulmonary capillary pressures and the onset of dyspnoea may be driven by the reduction of left atrial compliance, which can be assessed by peak atrial longitudinal strain (PALS) derived from speckle tracking echocardiography. Aim To assess the role of left atrial function as a determinant of symptoms in patients with severe degenerative MR. Methods We analysed retrospectively all patients affected by severe degenerative MR evaluated for cardiac surgery between May 2019 and July 2022 at IRCCS San Raffaele Hospital. The cohort was divided in symptomatic (NYHA &amp;gt;I) and asymptomatic (NYHA =I) patients. A comprehensive assessment of LA function was performed including pulmonary venous blood flow, LA ejection fraction, LA fractional atrial change, and PALS. Patients with atrial fibrillation during echocardiographic evaluation, left ventricular disfunction and more than mild left heart valvulopathy associated with MR were excluded. Results The final study population consisted of 408 patients. The grade of MR, assessed by multiparametric approach, was not different between the two groups. Age, history of coronary artery disease, dyslipidaemia, hypertension and history of atrial fibrillation were found to be predictive on symptomatology. Fractional area change (OR: 0.89; CI:0.87–0.91, p &amp;lt;0.001), atrial ejection fraction (OR: 0.92, CI= 0.90–0.94, p &amp;lt;0.001), atrial volume(OR: 1.04, CI: 1.02–1.05, p&amp;lt;0.001), pulmonary artery systolic pressure(OR:1.09, CI:1.06–1.13, p&amp;lt;0.001) and longitudinal atrial strain (OR:0.88, CI:0.85–0.90, p&amp;lt;0.001) but not EROA ( OR:1.06, CI: 0.63–2.30, p = 0.8) were found to be predictive. On multivariate logistic regression, only indexed biplane LA volume (OR: 1.02, CI 1.00–1.07, p = 0.035) and PALS (OR: 1.02, CI: 0.87–0.94, p&amp;lt;0.001) were found to be predictive. The best PALS threshold to identify symptomatic patients was 22% (OR: 3.3, SE 67%, SP 87%). Conclusions LA function is a determinant of symptoms in severe degenerative MR. The reduction of PALS appears to be a predictor of symptoms and a value of PALS &amp;lt; 22% identified symptomatic patients with 85% specificity and 67% sensitivity.

Clinical and prognostic implications of cardiopulmonary exercise stress echocardiography in asymptomatic degenerative mitral regurgitation

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The Saudi Arabian Cultural Bureau. Background Current guidelines recommend intervention in severe degenerative mitral regurgitation (MR) in symptomatic patients or asymptomatic patients with left ventricular dilatation or dysfunction. The insidious onset of symptoms may mean patients do not report symptoms. The role of systematic exercise testing for symptoms in MR is not clearly defined. Methods 97 patients with moderate to severe, asymptomatic MR underwent exercise echocardiography combined with cardiopulmonary exercise testing. Predictors of exercise-induced dyspnoea, symptom-free survival and mitral valve intervention were identified. Results 18 (19%) patients developed limiting dyspnoea on exercise. Spontaneous symptom free survival at 24 months was significantly higher in those without exercise-induced symptoms compared to those with exercise-induced symptoms, p &amp;lt;0.0001. The only independent predictors of spontaneous symptoms at 2 years were effective regurgitant orifice area (odds ratio 27.45 (95% CI 1.43 – 528.40), p = 0.03) and exercise-induced symptoms (odds ratio 11.56 (95% CI 1.71 – 78.09), p = 0.01). The only independent predictor of surgery was indexed left ventricular systolic volumes (Odds ratio 1.17 (95% CI 1.04 – 1.30), p = 0.006). Where only patients undergoing surgery due to symptoms were included, the only independent predictor was exercise-induced symptoms (Odds ratio 13.94 (95% CI 1.39 – 140.27), p = 0.025). Conclusion In patients with primary asymptomatic degenerative MR, one fifth develop symptoms on exercise. This predicts subsequent development of spontaneous symptoms and mitral valve intervention due to symptoms.

Transcatheter Mitral Valve Repair for Degenerative Mitral Regurgitation

There are limited data on the outcomes of transcatheter edge-to-edge mitral valve repair for degenerative mitral regurgitation (MR) in a real-world setting. To evaluate the outcomes of transcatheter mitral valve repair for degenerative MR. Cohort study of consecutive patients in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies Registry who underwent nonemergent transcatheter mitral valve repair for degenerative MR in the US from 2014 through 2022. Transcatheter edge-to-edge mitral valve repair with the MitraClip device (Abbott). The primary end point was MR success, defined as moderate or less residual MR and a mean mitral gradient of less than 10 mm Hg. Clinical outcomes were evaluated based on the degree of residual MR (mild or less MR or moderate MR) and mitral valve gradients (≤5 mm Hg or >5 to <10 mm Hg). A total of 19 088 patients with isolated moderate to severe or severe degenerative MR who underwent transcatheter mitral valve repair were analyzed (median age, 82 years; 48% women; median Society of Thoracic Surgeons predicted risk of mortality with surgical mitral valve repair, 4.6%). MR success was achieved in 88.9% of patients. At 30 days, the incidence of death was 2.7%; stroke, 1.2%; and mitral valve reintervention, 0.97%. MR success compared with an unsuccessful procedure was associated with significantly lower mortality (14.0% vs 26.7%; adjusted hazard ratio, 0.49; 95% CI, 0.42-0.56; P < .001) and heart failure readmission (8.4% vs 16.9%; adjusted hazard ratio, 0.47; 95% CI, 0.41-0.54; P < .001) at 1 year. Among patients with MR success, the lowest mortality was observed in patients who had both mild or less residual MR and mean mitral gradients of 5 mm Hg or less compared with those with an unsuccessful procedure (11.4% vs 26.7%; adjusted hazard ratio, 0.40; 95% CI, 0.34-0.47; P < .001). In this registry-based study of patients with degenerative MR undergoing transcatheter mitral valve repair, the procedure was safe and resulted in successful repair in 88.9% of patients. The lowest mortality was observed in patients with mild or less residual MR and low mitral gradients.

Edge-to-Edge Transcatheter Mitral Valve Repair Using PASCAL vs. MitraClip: A Systematic Review and Meta-Analysis.

Transcatheter edge-to-edge repair (TEER) of the mitral valve (MV) can be performed using the PASCAL or MitraClip devices. Few studies offer a head-to-head outcome comparison of these two devices. PubMed, EMBASE, Cochrane Library, Clinicaltrials.gov and WHO's International Clinical Trials Registry Platform, from 1 January 2000 until 1 March 2023, were searched. Study protocol details were registered in the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42023405400). Randomized Controlled Trials and observational studies reporting head-to-head clinical comparison of PASCAL and MitraClip devices were eligible for selection. Patients with severe functional or degenerative mitral regurgitation (MR) who had undergone TEER of the MV with either PASCAL or MitraClip devices were included in the meta-analysis. Data from six studies (five observational and one randomized clinical trial) were extracted and analyzed. The main outcomes were a reduction in MR to 2+ or less, improvement of New York Heart Association (NYHA) and 30-day all-cause mortality. Peri-procedural mortality, success rate and adverse events were also compared. Data from 785 and 796 patients that underwent TEER using PASCAL and MitraClip, respectively, were analyzed. Thirty-day all-cause mortality (Risk ratio [RR] = 1.51, 95% CI 0.79-2.89), MR reduction to maximum 2+ (RR = 1.00, 95% CI 0.98-1.02) and NYHA improvement (RR = 0.98, 95% CI 0.84-1.15) were similar in both device groups. Both devices had high and similar success rates (96.9% and 96.7% for the PASCAL and MitraClip group, respectively, p value = 0.91). MR reduction to 1+ or less at discharge was similar in both device groups (RR = 1.06, 95% CI 0.95-1.19). Composite peri-procedural and in-hospital mortality was 0.64% and 1.66% in the PASCAL and MitraClip groups, respectively (p value = 0.094). Rates of peri-procedural cerebrovascular accidents were 0.26% in PASCAL and 1.01% in MitraClip (p value = 0.108). Both PASCAL and MitraClip devices have high success and low complication rates for TEER of the MV. PASCAL was not inferior to MitraClip in reducing the MR level at discharge.

Data-driven mortality risk prediction of severe degenerative mitral regurgitation patients undergoing mitral valve surgery.

The outcomes of mitral valve replacement/repair (MVR) in severe degenerative mitral regurgitation (MR) patients depend on various risk factors. We aimed to develop a risk prediction model for post-MVR mortality in severe degenerative MR patients using machine learning. Consecutive severe degenerative MR patients undergoing MVR were analysed (n = 1521; 70% training/30% test sets). A random survival forest (RSF) model was constructed, with 3-year post-MVR all-cause mortality as the outcome. Partial dependency plots were used to define the thresholds of each risk factor. A simple scoring system (MVR-score) was developed to stratify post-MVR mortality risk. At 3 years following MVR, 90 patients (5.9%) died in the entire cohort (59 and 31 deaths in the training and test sets). The most important predictors of mortality in order of importance were age, haemoglobin, valve replacement, glomerular filtration rate, left atrial dimension, and left ventricular (LV) end-systolic diameter. The final RSF model with these six variables demonstrated high predictive performance in the test set (3-year C-index 0.880, 95% confidence interval 0.834-0.925), with mortality risk increased strongly with left atrial dimension >55 mm, and LV end-systolic diameter >45 mm. MVR-score demonstrated effective risk stratification and had significantly higher predictability compared to the modified Mitral Regurgitation International Database score (3-year C-index 0.803 vs. 0.750, P = 0.034). A data-driven machine learning model provided accurate post-MVR mortality prediction in severe degenerative MR patients. The outcome following MVR in severe degenerative MR patients is governed by both clinical and echocardiographic factors.