Etiology Of Mitral Regurgitation Research Articles

Outcomes of patients with severe mitral regurgitation treated with transcatheter mitral valve implantation or medical therapy

Abstract Funding Acknowledgements Type of funding sources: None. Background Patients with severe mitral regurgitation (MR) unsuitable for standard therapy (i.e., open-heart surgery and transcatheter edge-to-edge repair [TEER]), often remain on medical therapy (MT) alone. Transcatheter mitral valve implantation (TMVI) may represent an alternative treatment option for these patients. Purpose We aimed to investigate differences in anatomical baseline characteristics and echocardiographic outcomes between MR patients unsuitable for standard therapy, that were either treated with TMVI or remained on MT. Methods Between 05/2016-02/2021, 121 high-risk patients with severe MR were evaluated for TMVI. Clinical, echocardiographic and functional outcomes between the subgroups of patients treated with TMVI and MT were compared. The primary combined endpoint was all-cause death or heart failure (HF) hospitalization at 1 year. Subgroup analyses were performed to define specific patient subsets favouring either TMVI or MT. Results At baseline, there were no differences between the TMVI group (n = 38) and the MT group (n = 44) regarding age (all TMVI vs. MT: 77.0 years [IQR 72.9, 80.1] vs. 79.0 [IQR 76.0, 81.7], p = 0.13), gender (42.1% female vs. 56.8% female, p = 0.27) and estimated surgical risk (EuroSCORE II 4.4% [IQR 2.8, 13.6] vs. 6.4 [IQR 3.4, 10.1], p = 0.72). Patients undergoing TMVI were more frequently treated for secondary MR (68.4%), while primary MR was the most prevalent MR etiology in patients remaining on medical therapy (50.0%). Left ventricular (LV) end-diastolic diameters (LVEDD) were larger and LV ejection fraction (LVEF) was lower in the TMVI group (LVEDD 58.0mm [IQR 51.4, 65.0], LVEF 37.0% [IQR 31.4, 51.2]) compared to the MT group (LVEDD 52.0mm [IQR 46.2, 58.8], LVEF 54.5% [IQR 40.8, 60.0]) (p = 0.02 for LVEDD, p < 0.001 for LVEF). MR was effectively reduced to ≤ mild MR in all patients undergoing TMVI. In the MT group, MR remained severe in 90% of patients after 1 year. The primary composite endpoint occurred numerically more often in the MT group (72.2%) compared to the TMVI group (51.6%, p = 0.061). Regarding the primary endpoint, the subgroups of patients with LVEF 30-49% (HR 0.28 [95%-CI 0.11-0.67], p = 0.004), effective regurgitant orifice area (EROA) <0.4 cm2 (HR 0.30 [95%-CI 0.13-0.71], p = 0.006), tricuspid annular plane systolic excursion (TAPSE) ≥17mm (HR 0.27 [95%-CI 0.11-0.67], p = 0.005) and New York Heart Association functional class III (HR 0.38 [95%-CI 0.18-0.81], p = 0.012) were more likely to benefit from TMVI compared to MT. Conclusions In patients with severe MR unsuitable for standard therapy, TMVI represents a reasonable therapeutic alternative yielding effective elimination of MR. While most patients eligible for TMVI suffer from secondary MR, the majority of patients remaining on MT has primary MR. The primary endpoint occurred numerically, yet not statistically, more often in patients on MT. Baseline echocardiography was able to identify subgroups of patients with beneficial outcome after TMVI.

Minimally Invasive Mitral Valve Surgery After Transcatheter Edge-to-Edge Repair.

Up to 28% of patients may need mitral valve (MV) surgery after transcatheter edge-to-edge repair (TEER). This study evaluates the outcomes of minimally invasive MV surgery after TEER. Methods: International multicenter registry of minimally invasive MV surgery after TEER between 2013 and 2020. Subgroups were stratified by the number of devices implanted (≤1 vs >1), as well as time interval from TEER to surgery (≤1 year vs >1 year). Results: A total of 56 patients across 13 centers were included with a mean age of 73 ± 11 years, and 50% were female. The median Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) score for MV replacement was 8% (Q1-Q3 = 5% to 11%) and the ratio of observed to expected mortality was 0.9. The etiology of mitral regurgitation (MR) prior to TEER was primary MR in 75% of patients and secondary MR in 25%. There were 30 patients (54%) who had >1 device implanted. The median time between TEER and surgery was 252 days (33 to 636 days). Hemodynamics, including MR severity, MV area, and mean gradient, significantly improved after minimally invasive surgery and sustained to 1-year follow-up. In-hospital and 30-day mortality was 7.1%, and 1-year actuarial survival was 85.6% ± 6%. Conclusions: Minimally invasive MV surgery after TEER may be achieved as predicted by the STS PROM. Most patients underwent MV replacement instead of repair. As TEER is applied more widely, patients should be informed about the potential need for surgical intervention over time after TEER. These discussions will allow better informed consent and post-procedure planning.

Prognostic significance of right ventricle to pulmonary artery coupling in patients with mitral regurgitation treated with the MitraClip system.

To evaluate the prognostic impact of baseline tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio, as an expression of the right ventricle-pulmonary artery (RV-PA)coupling, in patients with mitral regurgitation (MR) treated with the MitraClip. Impaired RV to PA coupling is considered a marker of RV dysfunction. From February 2016 to February 2020, a total of 165 patients were evaluated and stratified in two groups according to a prespecified value of TAPSE/PASP ratio ≤ 0.36. The median patients' age was 79 (men: 62.4%). Sixty-three patients (38.1%) presented TAPSE/PASP ≤ 0.36 and were then compared with patients with TAPSE/PASP > 0.36. Functional MR etiology was more frequent in TAPSE/PASP ≤ 0.36 (71.4%; p = 0.046). Acute technical success was achieved in 92.7% of the population, without any significant difference between the two groups of study and with sustained results at 30-day (device success: 85.5%; procedural success: 84.8%). On multivariate Cox regression analysis, after correction for body mass index, chronic kidney disease and left ventricle ejection fraction ≥30% but <50%, TAPSE/PASP ≤ 0.36 remained a sustained predictor of mortality and hospitalization for heart failure at one year after MitraClip (hazard ratio: 3.87; 95% confidence interval: 1.83-8.22; p ≤ 0.001). Kaplan-Meier all-cause mortality and heart failure hospitalization rates at one year were consequently higher in patients with TAPSE/PASP ≤ 0.36 (39.4% vs. 14.8%; log-rank p ≤ 0.001). Baseline TAPSE/PASP ratio seems independently associated with all-cause mortality and heart failure hospitalization after MitraClip both in functional and degenerative MR.

608 The VCX Index: a novel haemodynamic quantification of mitral regurgitation

Abstract Percutaneous edge-to-edge mitral valve (MV) repair is extensively used in different pathological MV conditions. Randomized controlled trials have evaluated the role of this technique in both primary (organic) and secondary (functional) mitral regurgitation (MR). Furthermore, recent analyses of these studies have shown the relevance of echocardiographic patient selection in the functional setting of MR, differentiating proportionate MR from disproportionate MR according to the degree of the effective regurgitant orifice area (EROA) related to the left ventricular volume. The haemodynamic impact of MR cannot be univocally measured by echocardiography alone and the aim of our study was to determine how invasive LAP monitoring during percutaneous edge-to-edge MV repair can predict long-term procedural success on top of the echocardiographic assessment by introducing the VCX INDEX and identifying haemodynamic variables with direct influence on filling pressures. The VCX INDEX, reflecting the impact of MR, is calculated by dividing the difference between v wave (ventricular systole in the left atrial pressure, LAP, or in the pulmonary capillary wedge pressure, PCWP, waveform) and the mean minimum LAP or mean minimum PCWP (mean between minimum LAP or minimum PCWP, x wave, and a/c wave) by systolic arterial pressure (SAP): (v wave – mean minimum LAP or mean minimum PCWP)/SAP. 85 patients at our centres underwent invasive intracardiac pressure monitoring either measuring LAP during percutaneous edge-to-edge MV repair or PCWP during right heart catheterization. Median VCX INDEX was 0.1 (Q1 0.05, Q3 0.16). The study population was further analysed according to the echocardiographic aetiology of MR: in the organic MR subgroup median VCX INDEX was 0.08 (Q1 0.05, Q3 0.14), in the functional proportionate MR subgroup median VCX INDEX was 0.07 (Q1 0.03, Q3 0.13) and in the functional disproportionate MR subgroup median VCX INDEX was 0.11 (Q1 0.06, Q3 0.19). 20 patients were deemed inoperable by the Heart Team and no further intervention was performed, while 65 patients underwent percutaneous edge-to-edge MV repair with MitraClip device and VCX INDEX was recalculated after the procedure. Median post-MitraClip VCX INDEX was 0.04 (Q1 0.02, Q3 0.07) and a subanalysis based on the echocardiographic MR aetiology was repeated: median post-MitraClip VCX INDEX was 0.02 in the organic MR subgroup (Q1 0.01, Q3 0.05), 0.03 in the functional proportionate MR subgroup (Q1 0.02, Q3 0.07) and 0.05 in the functional disproportionate MR subgroup (Q1 0.03, Q3 0.07). Median VCX INDEX in patients who did not undergo MitraClip implantation was 0.07 (Q1 0.04, Q3 0.12). The variation of VCX INDEX when comparing pre- and post-procedural invasive pressure assessment gives an insight of MitraClip’s favourable haemodynamic effect in terms of VCX INDEX reduction in the treated subgroup of the study and how the intervention has a comparable haemodynamic impact between different echocardiographic MR aetiologies. Further studies are needed to explore the incremental diagnostic role in the decision-making process as well as the prognostic value of the VCX INDEX in patients undergoing percutaneous edge-to-edge MV repair.

Mitral Valve Regurgitation After Lung Transplantation: Aetiology, Management and Outcome

Problematic mitral regurgitation (MR) may develop following lung transplantation (LTx). There is limited information on the management of MR in LTx patients, as such we sought to evaluate our centre's experience. From 2000 to 2019, 1,054 patients underwent LTx at our centre (896 bilateral, 158 single). We identified patients in whom significant MR developed at any point post-LTx. The aetiology of MR, management and outcome were retrospectively analysed. Eight (8) patients developed severe MR post-LTx, six following bilateral LTx and two following single LTx. Lung transplantation indications included interstitial lung disease (n=5), chronic obstructive pulmonary disease (n=2) and pulmonary arterial hypertension (n=1). Severe MR occurred intraoperatively (n=1), postoperative day 1 (n=1) with the remaining six cases between 80 and 263 days post-LTx. The aetiology was noted to be due to severe left ventricular dysfunction following unmasking of a chronically pulmonary hypertension-related under-preloaded left ventricle in one case, and in the remaining seven patients causes included myxomatous degeneration, ischaemic MR, and functional MR due to annular dilatation. In the patient with intraoperative severe MR, the MR became mild with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and in the remaining seven patients a variety of procedures were used, including mitral valve repair, valve replacement and transcatheter edge-to-edge mitral valve repair. All patients survived the mitral procedure. Two (2) deaths occurred at 12.9 years (stroke) and 5 years (cancer) from mitral valve surgery. Development of significant mitral valve regurgitation is a rare but morbid complication after lung transplantation. This may represent the progressive natural history of pre-existing degenerative mitral valve disease and rarely, early after transplantation may be related to changes in ventricular geometry. Management of severe MR can follow the same management approach as in the non-transplant community, with the expectation of similarly good results.

Abstract 9545: Indexing Mitral Regurgitant Volume to Left Ventricular Cavity Size Improves Prognostication of Mortality

Background: Indexing mitral regurgitation (MR) regurgitation volume (RVol) for left ventricular (LV) cavity size accounts for concomitant LV remodeling, but whether it improves prognostication of mortality is uncertain. Methods: The ratio of RVol to LV end-diastolic diameter (LVDD) was measured in 399 individuals (mean age 70.1 ±16.4 years, 51.1% female) with any MR (mean RVol 49.2 ± 27.7 mL) undergoing echocardiography (TTE). Individuals with prior mitral valve interventions were excluded. The relationship between RVol/LVDD and all-cause mortality was examined. The incremental predictive value of RVol/LVDD was compared to RVol alone. Results: Over a median (interquartile range) of 8.8 (3.4-10.5) years follow-up, there were 101 deaths (25.3%). Amongst those treated medically (N = 348), a lower ratio was associated with higher mortality (HR per 1-mL/cm decrease, 1.04, 95% CI 1.01-1.10, p = 0.04), despite a lesser degree of MR (low vs. high RVol/LVDD group, mean RVol, 30.3 ± 11.7 mL vs. 68.1 ± 26.3 mL, p &lt; 0.001), with an inflection for increased risk &lt; 8.4 mL/cm ( Figure ). By contrast, amongst those treated surgically (N = 41), no association was observed (p = 0.69) between RVol/LVDD and mortality, though death was less frequent. This association with risk was observed only amongst individuals with a reduced LVEF and was independent of etiology of MR (e.g. secondary vs. primary). Compared to RVol alone, indexing for LV cavity size improved the prognostication of death (p &lt; 0.001). Conclusions: Amongst patients with MR with a reduced LVEF, treated medically, survival was significantly worse amongst individuals with lower RVol/LVDD ratios. Furthermore, indexing for LV cavity size improved prediction of mortality compared to RVol alone. These results overall suggest that RVol should be routinely indexed for LV size to improve prognostication of risk. Moreover, they suggest a threshold may exist where LV size predominates risk in individuals with MR, treated medically.

Percutaneous edge-to-edge therapy with PASCAL or MitraClip: a multicenter propensity score matched comparison

Abstract Background The MitraClip is the worldwide established transcatheter edge-to-edge repair system with over 100,000 treated patients. The recently approved PASCAL repair system is well adopted in the field of percutaneous mitral regurgitation (MR) treatment with growing acceptance both in mitral and tricuspid valves. The aim of this retrospective multicenter study was to compare the Edwards' PASCAL System with the Abbott MitraClip System in terms of procedural results and short-term outcome. Methods We retrospectively evaluated patient data of three high volume German centers that performed percutaneous edge to edge procedures either with the MitraClip or the PASCAL repair system. Primary endpoint was the amount of MR reduction. Secondary endpoints were residual MR at discharge, technical success, device success and 30-day mortality. Results Between 2018 and 2020 a total of 412 procedures were performed in the three centers. 216 cases were performed with the MitraClip compared to 196 procedures done with the PASCAL repair system. Patients were male in 55.6% of the cases (50.5% in the MitraClip cohort compared to 61.2% in the PASCAL cohort, p=0.028), mean Logistic Euro-Score II was 4.42 (3.58 in the MitraClip and 3.23 in the PASCAL cohort, p=0.038) and reduced LVEF beyond 45% was seen in 42.6% of the cases (49.5% in the MitraClip compared to 35.3% in the PASCAL cohort, p=0.004). Severe MR at baseline was seen in 98.5% in the MitraClip cohort compared to 98.6% in the PASCAL cohort, p=0.909). Mean number of implanted devices was 1.41±0.56 in the MitraClip cohort and 1.37±0.55 in the PASCAL cohort (p=0.401). Procedures were successfully conducted with both edge-to-edge systems (device success rate 93.2% in the MitraClip cohort and 94.0% in the PASCAL cohort, p=0.775), leading to comparably good results (final MR ≤2 in 94.4% with the MitraClip compared to 95.9% with the PASCAL system, p=0.448) and very good results (final MR ≤1 in 72.6% in the MitraClip compared to 79.5% in the PASCAL cohort, p=0.102). After propensity score matching for adjustment of major differences among the two treatment strategies (including age, gender, MR etiology, EROA, Severe MR (III and IV), reduced LVEF and Mitral Valve orifice area) the achieved mean MR reduction remains comparable (2.29±0.82 with the MitraClip compared to 2.46±0.82 with the PASCAL system, p=0.191). In multivariate regression analysis STS Score independently correlates with a very good final result while device choice did not show a significant impact in this cohort. Conclusion In this retrospective multicenter study both the MitraClip and PASCAL system performed excellent with comparable procedural success rates. Achieved final average reduction of MR Grade was 2.29±0.82 with the MitraClip and 2.46±0.82 with the PASCAL system. Funding Acknowledgement Type of funding sources: None.

Impact of right ventricular function and ventriculo-arterial coupling in prognosis after percutaneous edge-to-edge mitral repair

Abstract Background Left ventricular systolic function is widely used as selection criteria for appropriateness of percutaneous edge-to-edge mitral repair in patients with significant mitral regurgitation (MR) and high surgical risk. Although right ventricular (RV) systolic function and ventriculo-arterial coupling (VAC) have demonstrated its relevance in heart failure prognosis as well, few data are available regarding this procedure. Purpose To study the value of baseline RV function and VAC determined by transthoracic echocardiogram (TTE) on imaging and clinical prognosis. Methods We evaluated all the consecutive patients in which a percutaneous mitral edge-to-edge repair with the MitraClip system was performed between 2010 and 2020 in our tertiary university hospital. Baseline RV function was considered depressed if TAPSE &amp;lt;16 mm, tissue Doppler S'&amp;lt;9.5 cm/s or fractional area change (FAC) &amp;lt;35% on TTE. VAC was calculated as ratio of TAPSE by pulmonary artery systolic pressure (PASP) from the same studies. Follow-up echocardiographic measurements were evaluated and clinical events were collected from medical records. Results We included 88 patients (64.8% males, 76±10 years) with MR grade ≥3. MR etiology was classified as functional 44.3%, organic in 35.2% and mixed in 20.5%. Previous to the procedure left ventricular systolic function was mildly depressed (LVEF 44.5±15.3%) and 33 patients (37.5%) showed an impaired RV systolic function. At 6 months TTE the prevalence of RV dysfunction lower to 27.3%. Patients with initial RV systolic dysfunction showed greater improvement in TAPSE (3.2 vs −0.53 mm; p=0.052) and FAC (8 vs 0.2%; p=0.016) at 6 months compared to those with normal baseline RV function. However, this variable was not associated with any relevant clinical event during the follow up. Baseline VAC demonstrated a significant inverse correlation with change in TAPSE (r −0.42; p=0.018), FAC (r −0.37; p=0.024) and S' (r −0.52; p=0.041) at 6 months. Among patients with initial RV impairment, VAC was lower in those who persisted with RV systolic dysfunction at 6 months (0.41 vs 0.49; p=0.054). Moreover, VAC was significantly associated with NYHA class ≥3 (0.48 vs 0.63; p=0.042) and cardiovascular hospitalization (0.53 vs 0.63; p=0.07), with a correlation with number of admissions (r −0.27; p=0.053). Conclusion In a percutaneous mitral edge-to-edge repair population previous presence of RV systolic dysfunction was not associated with clinical events during the follow up. Conversely, VAC was able to identify RV systolic function recovery and was associated with functional class and cardiovascular hospitalizations. Funding Acknowledgement Type of funding sources: None.

Long-Term survival and functional status in patients with elevated mitral valve pressure gradient after transcatheter mitral valve repair

Abstract Background A growing number of patients are currently treated for severe mitral regurgitation (MR) using a transcatheter mitral valve repair (TMVr). In clinical routine, the potential risk of elevated post-procedural mitral valve pressure gradient (MPG) may prohibit optimal MR reduction driven by the avoidance of additional clip implantations. Thus, the unfavorable impact on survival and functional outcome of increased MPG in patients undergoing TMVr is currently debatable. Methods In this single-center, prospective study, survival and functional outcome of 780 consecutive patients with severe MR undergoing TMVr between September 2008 and January 2020 were investigated. After exclusion of patients with unsuccessful procedure and those lost to follow-up, data of 676 patients with a median follow-up time of 5.26 (5.11, 5.51) years were analyzed. MPG was determined by transthoracic echocardiography at discharge and considered elevated in excess of 4.5 mmHg. Kaplan-Meier analysis as well as multivariable Cox regression models were performed for the impact on elevated MPG on 5-year outcomes for the subgroups of functional MR (FMR) and degenerative MR (DMR). The primary outcome measure was a combined endpoint of death or rehospitalization for congestive heart failure. Results Among 676 patients undergoing TMVr (mean age 74.6±8.5 years, 59.0% male, median STS Score 3.9 [interquartile range 2.5; 6.0]), 179 (26.4%) patients had elevated MPG &amp;gt;4.5 mmHg. FMR was present in 426 (63.0%) patients. In the overall patient cohort, Kaplan-Meier and Cox Regression analyses could not demonstrate significant differences for the combined endpoint (p=0.99). In contrast, subgroup analysis according to MR etiology indicated a significant adverse influence of elevated MPG on the combined endpoint as well as functional outcome in patients with DMR, but not with FMR (Figure 1). After adjustment, multivariate Cox Regression analysis showed an inferior prognosis in patients with DMR and elevated MVPG &amp;gt;4.5 mmHg (hazard ratio 1.79 [1.17, 2.72], p=0.0069, Figure 2). Conclusions TMVr-patients with DMR and measurable elevated post-procedural MVPG face an inferior prognosis and reduced functional outcomes compared to patients with FMR. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Periprocedural changes in natriuretic peptide levels and clinical outcome after transcatheter mitral valve repair.

AimsThis multicentre study investigated the association of periprocedural changes in the levels of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) with clinical outcomes after transcatheter edge‐to‐edge mitral valve repair (TMVR).Methods and resultsPatients were retrospectively analysed who underwent TMVR with the MitraClip system (Abbott Vascular, Santa Clara, CA, USA) and had available sequential NT‐proBNP testing at baseline and 2 months after TMVR. Periprocedural changes in NT‐proBNP following TMVR were assessed as the percent change in NT‐proBNP between baseline and the 2 month follow‐up, and the significant reduction in NT‐proBNP was defined as a decrease of >30% in the follow‐up NT‐proBNP compared with the pre‐procedural NT‐proBNP level. Primary outcome was defined as a composite outcome consisting of all‐cause mortality and hospitalization due to heart failure from 2 months to 2 years after TMVR. Additionally, we identified the cut‐off value of pre‐procedural NT‐proBNP to predict the composite outcome using a receiver operating characteristic analysis (cut‐off: 2485 pg/mL). Of 485 patients undergoing TMVR (age: 76.2 ± 9.2 years, female: 42.1%, secondary mitral regurgitation: 67.2%), 150 patients (30.9%) had the significant reduction in NT‐proBNP (>30%) following the procedure. Patients with the NT‐proBNP reduction had a lower incidence of the composite outcome, compared with those without the reduction in NT‐proBNP (31.4% vs. 40.2%; log‐rank P = 0.03). The significant reduction in NT‐proBNP was also associated with a lower risk of the composite outcome [adjusted hazard ratio (HR): 0.67; 95% confidence interval (CI): 0.45–0.97; P = 0.04], independently of pre‐procedural NT‐proBNP levels and other clinical parameters. The percent change in NT‐proBNP was associated with a linear trend of the incidence of the composite outcome (adjusted HR per 10% decrease: 0.96; 95% CI: 0.94–0.98; P < 0.001). A stratified analysis revealed that the prognostic impact of the significant reduction in NT‐proBNP was consistent among clinical subgroups, including aetiology of mitral regurgitation (P for interaction = 0.99). Higher pre‐procedural NT‐proBNP level (>2485 pg/mL) was associated with the increased risk of the composite outcome (adjusted HR: 1.50; 95% CI: 1.03–2.17; P = 0.03); however, patients with a higher pre‐procedural NT‐proBNP who achieved the significant reduction in NT‐proBNP had a similar risk of the composite outcome to those with a lower pre‐procedural NT‐proBNP.ConclusionsChanges in sequential NT‐proBNP measurements were associated with clinical outcomes within 2 years after TMVR. The assessment of NT‐proBNP dynamics may be valuable to assess the residual risk for patients undergoing TMVR and could assist with post‐procedural management after TMVR.

Successful percutaneous mitral valve leaflet repair for primary mitral regurgitation results in functional improvement and positive cardiac reverse remodelling

Abstract Funding Acknowledgements Type of funding sources: None. Background Percutaneous mitral valve leaflet repair can be an effective treatment for primary mitral regurgitation (MR) patients deemed high-risk for surgery. Accurate assessment of cardiac reverse remodelling is essential to optimise future patient selection. Cardiovascular magnetic resonance (CMR) is the reference standard for cardiac volumetric assessment and compared to transthoracic echocardiography (TTE) provides superior reproducibility in MR quantification. Prior CMR studies have analysed cardiac reverse remodelling following percutaneous intervention in combined cohorts of primary and secondary MR patients. However, as aetiology of MR can significantly impact outcomes, focused studies are warranted. Purpose Assess cardiac reverse remodelling and quantify changes in MR following percutaneous mitral valve leaflet repair for primary MR using the reference standard (CMR). Methods 12 patients with at least moderate-severe MR on TTE were prospectively recruited to undergo CMR imaging and 6-minute walk tests (6MWT) at baseline and 6 months following percutaneous mitral valve leaflet repair (MitraClip). CMR protocol involved: left-ventricular (LV) short axis cines (bSSFP, SENSE-2, 10mm, no gap), transaxial right-ventricular (RV) cines (bSSFP, SENSE-2, 8mm, no gap), two and four chamber cines and aortic through-plane phase contrast imaging, planned at the sino-tubular junction. MR was quantified indirectly using LV and aortic stroke volumes. Results 12 patients underwent percutaneous mitral valve leaflet repair (MitraClip) for posterior mitral valve leaflet prolapse, however 1 patient declined follow up after single-leaflet clip detachment resulting in 11 patients (age 83 ± 5years, 9 male) completing follow up imaging. At 6-months: significant improvements occurred in New York Heart Association functional class (Table 1) and 6MWT distances (223 ± 71m to 281 ± 65m, p = 0.005) and significant reductions occurred in indexed left ventricular end-diastolic volumes (LVEDVi) (118 ± 21ml/m2 to 94 ± 27ml/m2, p = 0.001), indexed left ventricular end-systolic volumes (58 ± 19ml/m2 to 48 ± 21ml/m2, p = 0.007) and quantitated MR volume (55 ± 22ml to 24 ± 12ml, p = 0.003) and MR fraction (49 ± 9.4% to 29 ± 14%, p= &amp;lt;0.001). There were no statistically significant changes in left ventricular ejection fraction (LVEF), right ventricular dimensions/ejection fraction or bi-atrial dimensions (Table 1). All patients demonstrated decreased LVEDVi and quantified MR (Figure 1). Conclusion Successful percutaneous mitral valve leaflet repair for primary MR results in reduction in MR, positive LV reverse remodelling, preservation of LVEF, and functional improvements. Larger CMR studies are now required to further guide optimal patient selection.

The predictive value of intraprocedural mitral gradient for outcomes after MitraClip and its peri‐interventional dynamics

The current data on the impact of the increased mitral gradient (MG) on outcomes are ambiguous, and intraprocedural assessment of MG can be challenging. Therefore, we aimed to evaluate (a) peri-interventional dynamics of MG, (b) the impact of intraprocedural MG on clinical outcomes, and (c) predictors for unfavorable MG values after MitraClip. We prospectively included patients who underwent MitraClip. All patients underwent echocardiography at baseline, intraprocedurally, at discharge, and after 6months. 12-month survival was documented. One hundred and seventy five patients (age 81.2±8.2years, 61.2% male) with severe mitral regurgitation (MR) were included. We divided our cohort into two groups according to intraprocedural MG with a threshold of 4.5mmHg, determined by a multivariate analysis of predictors for 12-month mortality (<4.5mmHg: Group 1, ≥4.5mmHg: Group 2). Intraprocedural MG ≥4.5mmHg was found to be the strongest independent predictor for 12-month mortality (HR: 2.33, P=.03, OR: 1.70, P=.05), and >3.9mmHg was associated with adverse functional outcomes (OR: 1.96, P=.04). The baseline leaflet-to-annulus index >1.1 was found to be the strongest independent predictor (OR: 9.74, P=.001) for unfavorable intraprocedural MG, followed by the number of implanted clips (P=.01), MG at baseline (P=.02), and central clip implantation (P=.05). An intraprocedural MG <3.9mmHg appears to be the best strategy for 1-year survival and favorable functional outcomes after edge-to-edge MV repair with MitraClip independently from MR etiology. Peri-interventional echocardiographic and procedural parameters are useful for the adequate assessment of intraprocedural MG.

Comprehensive echocardiographic prediction of postprocedural transmitral pressure gradient following transcatheter mitral valve repair.

Iatrogenic mitral stenosis following transcatheter mitral valve repair (TMVR) for relevant mitral regurgitation (MR) is a potential adverse side-effect, known to affect long-term outcome. However, only few determinants of an elevated mean transmitral pressure gradient (TMPG) have been described thus far. We sought to develop an integrative model for the prediction of TMPG following MitraClip (MC) therapy. From 01/2013 to 03/2017, a total of 175 consecutive patients were successfully (MR ≤ 2 + at discharge) treated with a MitraClip implantation at our centre. Of these, a total of 148 patients (54% male, 77.0 ± 6.0years, 58% with secondary MR) had complete echocardiographic data sets comprising pre- and postinterventional two- and three-dimensional transthoracic (TTE) and transoesophageal (TOE) echocardiograms. Comprehensive studies of predefined parameters were performed. An expert-based prediction model including preprocedural variables (annular ellipticity, mitral valve commissure-to-commissure diameter, preprocedural transmitral pressure gradient and MR aetiology) was set up and validated with a total of 200 bootstrap samples. A nomogram was developed to predict the postprocedural TMPG based on selected echocardiographic variables. Introduction of nomogram-based guiding of MC therapy could help identify patients at risk for postprocedural mitral stenosis, have an influence on preprocedural patient selection and intraprocedural decision making.

Determinants of Exercise-Induced Mitral Regurgitation Using Three-Dimensional Transesophageal Echocardiography Combined With Isometric Handgrip Exercise

Using three-dimensional (3D) transesophageal echocardiography (TEE) and isometric handgrip exercise (IHE), we investigated the determinants of exercise-induced mitral regurgitation (MR) according to MR etiologies. Seventy-six patients with more than moderate MR, 40 patients with functional MR (FMR) and 36 patients with degenerative MR (DMR), underwent 3D TEE combined with IHE. Mitral valve (MV) geometry and 3D vena contracta area (3D VCA) were simultaneously evaluated at baseline and during IHE. With regard to exercise-induced MR, Δ3D VCA was calculated as the difference between 3D VCA at baseline and 3D VCA during IHE. IHE caused different changes in MV geometry between etiologies and led to exacerbation of 3D VCA at baseline. Larger Δ3D VCA was observed in the FMR group compared with the DMR group (15.9 ± 10.3 mm2 versus 7.3 ± 4.2 mm2; p < 0.0001). In multivariate analyses, tenting height and 3D VCA were selected as independent factors associated with Δ3D VCA in the FMR group (p = 0.0135 and p = 0.0201, respectively), while flail width was selected as an independent factor associated with Δ3D VCA in the DMR group (p = 0.0066). In conclusion, IHE alters mitral valve geometry and causes exacerbation of MR regardless of MR etiology and the determinants of exercise-induced MR differed between MR etiologies.

Mitral valve repair in chronic severe mitral regurgitation: short-term results and analysis of mortality predictors.

Mitral valve repair is the accepted treatment for mitral regurgitation (MR) but lack of resources and socioeconomic concerns delay surgical referral and intervention in developing countries. We evaluated immediate and short-term results of mitral valve repair for non-ischemic MR at our centre and aimed to identify the predictors of in-hospital and follow-up mortality. The study was conducted at a tertiary-level hospital in South India. All patients >18years with severe non-ischemic MR who underwent mitral valve repair over a period of 6years were included. Perioperative data was collected from hospital records and follow-up data was obtained by prospective methods. There were 244 patients (170 males). Most of the patients were in the age group 31-60years (76.6%). Aetiology of MR was degenerative (n= 159; 65.2%), rheumatic (n= 34; 13.9%), structural (n= 42; 17.2%), or miscellaneous (n= 9; 3.7%). All patients underwent ring annuloplasty with various valve repair techniques. One hundred patients (44.7%) underwent additional cardiac procedures. At discharge, MR was moderate in 4 patients; the rest had no or mild MR. The mean hospital stay of survivors was 7.1days (SD 2.52, range 5-25days). There were 9 in-hospital deaths (3.68%) and 10 deaths during follow-up (4.2%). The mean follow-up period was 1.39years, complete for 87.6%. Pre-operativeleft ventricle ejection fraction(LVEF) <60% (p= 0.04) was found to be significantly associated with immediate mortality. Logistic regression analysis detected age (p= 0.019), female sex (p= 0.015), and left ventricular (LV) dysfunction at discharge (p= 0.025) to be significantly associated with follow-up mortality. Pre-operative LV dysfunction was identified as a significant risk factor for in-hospital mortality. Female sex, age greater than 45years, and LV dysfunction at discharge were found to be significantly associated with follow-up mortality. Hence, it is important to perform mitral valve repair in severe regurgitation patients before significant LV dysfunction sets in for a better outcome.

Prevalence, distribution, and determinants of pulmonary venous systolic flow reversal in severe mitral regurgitation.

This study aimed to evaluate the prevalence and distribution of pulmonary venous systolic flow reversal (PVSFR) in patients with severe mitral regurgitation (MR), and to examine the relationship between PVSFR profile and cardiac parameters. A total of 125 patients with severe MR who had transoesophageal echocardiography (TOE) performed were reviewed. Of these, 121 (96.8%) patients showed all four pulmonary venous (PV) flows by TOE. They were categorized into three groups by the MR aetiology: degenerative MR (DMR) (n = 72), ventricular functional MR (V-FMR) (n = 20), and atrial functional MR (A-FMR) (n = 16). Eighteen (16.7%) patients had PVSFR in all four PVs. Twenty-nine (26.9%) had PVSFR in three PVs, 23 (21.3%) in two PVs, and 23 (21.3%) in one PV. PVSFR appeared at right PVs more frequently compared with left PVs. A high number of PVSFR was significantly correlated with higher pulmonary capillary wedge pressure (PCWP) and 3D vena contracta area (3D-VCA). With regard to MR aetiology, the number of PVSFRs was correlated with high 3D-VCA in patients with DMR and A-FMR, while it was correlated with high PCWP in patients with V-FMR. Laminar-type PVSFR appeared more frequently in FMR compared with DMR, and it had a relationship with higher PCWP and lower right ventricular fractional area change (RVFAC). All four PV were detected in 96.8%, and 16.8% patients had PVSFR in all four PVs. PCWP and 3D-VCA were correlated with the number of PVSFRs in severe MR patients. Laminar-type PVSFR was related to higher PCWP and lower RVFAC.

Safety, effectiveness and costs of percutaneous mitral valve repair: A real-world prospective study.

AimsPercutaneous mitral valve leaflet repair is a treatment option for some people with severe mitral valve regurgitation for whom conventional mitral valve surgery is clinically inappropriate. This study aimed to determine the safety, efficacy, and costs of percutaneous mitral valve leaflet repair, using the MitraClip device in a UK setting.Methods and resultsThis was a prospective, single-armed registry with a follow-up of 2 years that reported a range of procedural, clinical and patient-orientated outcomes. Registry data were linked to routine data sources to allow for more comprehensive follow up concerning mortality and healthcare resource use. The registry received data for 199 mainly elective patients with mixed mitral regurgitation aetiology. A MitraClip device was implanted in 187 patients (94%), with a procedural success rate of 86%, with 8% of patients having a serious in-hospital adverse event (including 5% mortality). Percutaneous mitral valve leaflet repair reduced mitral regurgitation from 100% MR grade ≥ 3+ to 7% at discharge. There were corresponding improvements in New York Heart Association functional class, reducing from 92% (class ≥ 3) at baseline to 18% at 6 weeks. There were significant improvements in generic and disease specific quality of life indicators up to 2 years. The all-cause mortality rate was estimated to be 12.7% (95% CI 7.5 to 17.7%) at 1 year. Percutaneous mitral valve leaflet repair was associated with reduced hospital readmissions and potential cost-savings in post-procedural care.ConclusionThis study shows that percutaneous mitral valve leaflet repair using MitraClip is a relatively safe and effective treatment in patients unable to tolerate surgery and has the potential to reduce ongoing healthcare costs in the UK.

Italian Society of Interventional Cardiology (GIse) registry Of Transcatheter treatment of mitral valve regurgitaTiOn (GIOTTO): impact of valve disease aetiology and residual mitral regurgitation after MitraClip implantation.

The Italian Society of Interventional Cardiology (GIse) registry Of Transcatheter treatment of mitral valve regurgitaTiOn (GIOTTO) was conceived in order to assess the safety and efficacy of MitraClip therapy in Italy. The aim of this study was to assess procedural and mid-term outcomes, and clinical and echocardiographic predictors of mid-term mortality after MitraClip therapy, stratifying the results according to the diagnosis of functional and degenerative mitral regurgitation (FMR vs. DMR). Between January 2016 and March 2020, 1659 patients were prospectively included in the GIOTTO registry (FMR 59.4% vs. DMR 40.6%). Acute Mitral Valve Academic Research Consortium (MVARC) technical success was achieved in 97.2% of patients, without differences between FMR and DMR and with sustained results at 30 days. In the study population, all-cause mortality was 4.0%, 17.5% and 34.6% at 30 days, 1 year and 2 years, respectively. Cardiovascular death was the most frequent cause of mortality. Overall hospitalization rates were 6.3%, 23.4% and 31.7% at 30 days, 1 year and 2 years, respectively. The most frequent cause of hospitalization was heart failure, particularly in the first 30 days. FMR and MVARC structural and functional failure were strongly associated with 1-year mortality. Residual mitral regurgitation 1+ (rMR) was independently related to a reduced risk of 1-year mortality (hazard ratio 0.62; P=0.005). Coherently, at 2-year follow up, FMR was associated with worse outcomes than DMR, and Kaplan-Meier all-cause mortality was related to rMR. Functional mitral regurgitation aetiology affects 1-year mortality after MitraClip implantation, and differences in mortality and hospitalization rates between FMR and DMR can be observed within 2 years. Optimal rMR 1+ was correlated to a more favourable mid-term outcome, particularly in FMR.

Left atrial fibrosis: an essential hallmark in chronic mitral regurgitation

Abstract Chronic mitral regurgitation (MR) is the second valvular heart disease for incidence, which worsening severity gradually affects all cardiac chambers and leads to poor outcome if untreated. The recent development of minimally invasive surgical techniques and percutaneous intervention has reduced the operative risk, allowing a more confident referral of these patients for intervention. Therefore, there is a growing need of reliable markers to select the best therapeutic strategies and to identify the optimal timing for intervention. Myocardial fibrosis (MF) gradually occurs as a result of left atrial and ventricular (LA and LV) remodeling due to MR pressure and volume overload. It has been identified as an index of clinical outcome and arrhythmic risk in patients with MR. Particularly, the assessment of LA fibrosis not only allows to define different MR etiology, but also was associated with prognosis and atrial fibrillation (AF) burden. Nowadays, noninvasive estimation of MF is possible through the use of advanced imaging modalities, particularly cardiac magnetic resonance and speckle tracking echocardiography. This review discusses the role of LA fibrosis as a diagnostic and prognostic marker in patients with MR and its quantification by noninvasive multimodality cardiac imaging.

Impact on outcome of different etiologies, baseline degree and improvement of mitral regurgitation in patients with aortic stenosis who underwent transcatheter aortic valve replacement

Abstract Funding Acknowledgements Type of funding sources: None. Background - Mitral regurgitation (MR) is a frequent finding in patients with aortic stenosis (AS). Moderate or severe MR is present in up to one-third of pts undergoing TAVR and it is a negative prognostic factor as well as the presence of residual MR after TAVR. However, whether different etiologies/mechanisms of MR have different effects on outcome and MR degree changes after TAVR is yet unknown. Aim – The aim of the study is to evaluate the prognostic impact of baseline MR degree and its changes after TAVR procedures according to different etiologies of MR in patients who underwent TAVR. Methods - We performed a retrospective observational study on a cohort of patients who underwent TAVR between January 2015 and December 2019. During the index period 947 pts underwent TAVR. To better characterize the mechanism of MR only pts with pre-procedural 3D transesophageal echocardiographic and at least one follow-up available study were included. The final study population consisted of 224 pts. MR severity was evaluated by multiparametric approach and classified in 4 degrees. The study population was further divided in 4 groups: Group I: fibro-calcific degeneration of the leaflets (78.6% pts); 2. Group II: prolapse or flail (4.4% pts); Group III: functional MR (FMR) due to leaflets tethering (5.6% pts); Group IV: FMR due to annular dysfunction or dilatation (11.3% pts). Primary outcome was all-cause of death. Results and Discussion – MR was absent in 15 pts (6.7%), mild in 79 pts (35.7%), mild-to-moderate in 109 in pts (49.3%), moderate-to-severe in 7 pts (3.1%) and severe in 11 pts (4.9%). Patients with &amp;gt; moderate MR degree at baseline had a worse outcome than patients with &amp;lt; moderate MR degree (p log rank = 0.029). FMR (groups III and IV) was associated with better outcome than organic MR (groups I and II) (p log rank = 0.035). Moreover, group IV showed a better outcome compared groups I (p log rank = 0.047) and II (p log rank = 0.038). Patients who showed improvement of MR of at least 1 degree post TAVR showed better outcome compared to patients without improvement (p log rank = 0.04). At multivariate analysis, including pre procedural MR &amp;gt; 2+, pre procedural TR &amp;gt; 2+, organic vs functional etiology and MR improvement after TAVR as covariates, only baseline MR &amp;gt; moderate was an independent predictor of mortality (HR 6.3; 95% CI 1.4 -27.0; p &amp;lt; 0.001). Conclusion - This study confirms the prognostic role of the baseline degree of MR in patients with AS undergoing TAVR. Moreover, this is the first study demonstrating that FMR due to annular dilatation but not due to leaflet tethering is associated with better outcome compared to organic etiologies.