Functional Mitral Regurgitation In Patients Research Articles

P904 Impact of significant functional mitral regurgitation and aortic stenosis on outcome of HFrEF patients

Abstract Background Concomitant aortic stenosis (AS) and functional mitral regurgitation (FMR) are common in patients with left ventricular dysfunction. We evaluated the impact of significant valve diseases on outcome of patients with reduced left ventricular ejection fraction (HFrEF, LVEF < 40%). Methods A total of 1264 consecutive HFrEF patients referred to our department between 2009 and 2017 were screened. Transthoracic echocardiography was performed at baseline visit in all patients. Patients with primary MR or received mitral valve operation before or after baseline visit (n = 64) as well as patients underwent aortic valve replacement (AVR) before baseline visit (n = 66) were excluded. Finally, 1134 HFrEF patients were included for final analysis, and all completed a median clinical follow-up of 26 (12-40) months by medical record review or telephone interview. The primary endpoint was all-cause mortality or heart transplantation (HTx). Results Moderate or severe FMR or AS was detected in 902 (79.5%) and in 119 (10.5%) patients by echocardiography, respectively. Of patients with significant AS, 47 patients underwent AVR shortly after baseline visit. In total, 353 (31.2%, including HTx n = 11) HFrEF patients died or underwent HTx during follow-up. Age, body mass index, diabetes, atrial fibrillation, coronary artery disease, chronic respiratory diseases, and renal dysfunction (all P < 0.05) were defined as clinical covariates associated with all-cause mortality/HTx and served as potential confounders in the multivariable Cox regression models. All-cause mortality/HTx was significantly higher in HFrEF patients with significant FMR than patients without significant FMR (33.8% vs. 20.7%, P < 0.001). Multivariable Cox regression analysis showed significant FMR remained as an independent determinant of all-cause mortality/HTx in patients with HFrEF after adjusted for above mentioned confounders (HR 1.39, 95% CI 1.02-1.90, P = 0.035). Patients with significant AS without AVR faced increased risk of all-cause mortality/HTx as compared to patients without significant AS (HR 2.34, P < 0.001), while risk of all-cause mortality/HTx was significantly lower in patients with significant AS and underwent AVR as compared to patients without significant AS after adjustment for confounders (HR 0.36, P = 0.008). In the subgroup of HFrEF patients with significant FMR, significant AS without AVR was independently associated with increased all-cause mortality/HTx as compared to patients without significant AS (HR 2.30, P < 0.001), while outcome is better in AS and FMR patients underwent AVR as compared to patients with significant FMR and without significant AS (survival: 85.4% vs. 67.5%, P < 0.001; HR 0.34, P = 0.010) after adjustment for potential confounding factors. Conclusion Moderate to severe FMR and/or AS is incrementally related to higher all-cause mortality/HTx in HFrEF patients. AVR could significantly improve the survival of HFrEF patients with concomitant significant AS and FMR.

428 Prognostic implications of the relationship between effective regurgitant orifice area and left ventricle end diastolic volume in patients with functional mitral regurgitation treated with MitraClip

Abstract Funding Acknowledgements none Background The distinction between proportionate and disproportionate functional mitral regurgitation (FMR), based on the relationship between effective regurgitant orifice area (EROA) and left ventricle end diastolic volume (LVEDV), has recently been proposed as a possible new clinical and physiopathological framework to identify patients that could likely benefit from transcatheter mitral repair. Purpose The aim of our study was to explore the possible prognostic implications of the EROA/LVEDV ratio in patients with FMR treated with MitraClip. Methods – Baseline EROA/LVEDV was calculated in 137 patients with at least moderate-to-severe, symptomatic FMR treated with MitraClip. All patients underwent clinical, biochemichal and echocardiographic evaluation before MitraClip. EROA was calculated using PISA method. The primary outcome was a composite end-point of all-cause death or re-hospitalization for heart failure (HF). Results – The median follow-up was 1.1 years. The primary outcome occurred in 59 patients (43 %). Population study showed a LVEDVi 113.52± 32.16 mL/m2, LVEF 29.75± 10.06% and EROA 39.45± 15.43 mm2.. The cut-off value of EROA/LVEDV ratio for primary outcome, identified by receiver operating characteristic curve, was 0.15 (AUC 0,65, p = 0.002) with a sensitivity and specificity of 78% and 52%, respectively. Patients were divided in two groups according to the identified cut-off. Patients with higher ratio (Group I, n = 88) presented a less dilated LV (LVEDVi: 105.1 ± 29.6 mL/m2 vs 128.2 ± 31.9 mL/m2, p < 0.001; LVESVi: 73.1 ± 27.7 mL/m2 vs 94.9 ± 29.05 mL/m2, p < 0.001), and a more severe MR (EROA: 47.9 ± 12.1 mm2 vs 25.1 ± 8.3 mm2, p < 0.001; vena contracta: 7.2 ± 1.3 mm vs 6.5 ± 1.3 mm, p = 0.008). There were no significant differences of left ventricle ejection fraction, right ventricle systolic function and systolic pulmonary pressure between the groups. At univariate analysis, EROA/LVEDV ratio >0.15 (HR = 2.223, 95% CI 1.121-4.411, p = 0.022), baseline evidence of atrial fibrillation (HR = 1.949, 95% CI 1.156-3.283, p = 0.012) and baseline pro-BNP (HR= 1.000, 95% CI 1.000-1.000, p = 0,001) were associated with a worse clinical outcome. At multivariate Cox-regression analysis, both EROA/LVEDV ratio >0.15 and baseline pro-BNP values were identified as independent predictors (HR 2.941, 95% CI 1.035-8.353, p = 0.043; HR = 1.000, 95% CI 1.000-1.000, p = 0.002, respectively). At Kaplan-Meier survival analysis, patients with EROA/LVEDV >0.15 had a significant lower freedom from composite endpoint (log-rank χ2 =5.517, p= 0.019; Fig. 1). Conclusion Our data show that EROA/LVEDV ratio was an independent predictor of adverse clinical outcome in FMR patients treated with MitraClip. This preliminary experience shows that this index could help to identify subgroups of patients with potential different clinical benefits from Mitraclip therapy. However, further and extended data are needed to provide more precise evidence. Abstract 428 Figure. Fig. 1

P1364 Contractile reserve predicts reverse remodelling after successful percutaneous mitral valve repair in patients with functional mitral regurgitation

Abstract Background Recent randomised trials have shown conflicting results regarding the usefulness of percutaneous mitral valve repair using MitraClip in patients with severe functional mitral regurgitation (FMR). At present, it remains unclear whether patients with FMR and advanced heart failure might benefit from MitraClip therapy. Moreover, it has been shown that left ventricular reverse remodelling (LVRR) post-MitraClip is associated with a favourable outcome. Purpose We sought to assess whether baseline contractile reserve (CR) can predict LVRR and improvement of LV ejection fraction (EF) in FMR patients undergoing MitraClip therapy. Methods Consecutive patients with symptomatic severe FMR referred for MitraClip were recruited in two tertiary centres. All patients were scheduled for a semi-supine bicycle exercise echocardiography before and 6 months after the intervention. Patients who were not able to perform an exercise test and who did not complete 6 month follow up were excluded from further analysis. Baseline CR was obtained by subtracting peak exercise LVEF from LVEF at rest. LVRR was defined as a 10% decrease in LV end systolic volume (ESV) at follow-up. Results 34 patients completed 6 month follow up (61% male, age 71 ± 10 years, LVEF 32 ± 8%). LVRR was observed in 15 patients (44%). We found a trend towards a moderate correlation between baseline CR and relative decrease in LVESV at 6 months (Pearson Rho -0.321, p = 0.064). This correlation became significant in a sub-analysis considering only patients with post-procedural FMR grade ≤2 (n = 27; Pearson Rho -0.444, p = 0.020). In contrast, LVRR was not related to baseline LVEF, LV dimensions or volumes. Furthermore, baseline CR was strongly correlated with an increase of LVEF at 6 months post-MitraClip in these patients (Pearson Rho 0.653, p < 0.001). Conclusion CR predicts LVRR and improvement of LVEF in patients with FMR after successful MitraClip therapy (reduction of FMR towards grade ≤2), in contrast to resting indices of LV dysfunction and dilatation. More studies with outcome data are needed to determine whether CR is a useful parameter to identify patients with FMR who might benefit from MitraClip therapy.

Treatment of Functional Mitral Regurgitation in Heart Failure.

To analyze the current state of the art of functional mitral regurgitation (FMR) treatment. The first-line treatment of severe FMR consists of guideline medical therapy (GMT) and resynchronization therapy when indicated; the impact of new medical therapies like sacubitril/valsartan needs further assessment. Valvular intervention may be considered in FMR symptomatic patients despite GMT, and can be performed surgically or percutaneously. MitraClip is a safe percutaneous procedure associated with symptoms improvement. Recently, the COAPT trial showed superior outcomes for MitraClip versus GMT contrasting the MITRA-FR trial which showed no benefit of MitraClip compared with GMT. These results should be interpreted as complementary rather than opposite. The COAPT trial provided a "proof of concept" that percutaneous treatment of severe FMR in patients without too advanced left ventricular disease translates into a prognostic benefit. Careful patient selection will play a critical role in defining the clinical niche for successful interventions.

P3764Morphological mechanisms of atrial functional mitral regurgitation in patients with atrial fibrillation

Abstract Background Atrial functional mitral regurgitation (AFMR) occurs in patients with atrial fibrillation. However, morphological mechanisms of AFMR are poorly understood. Purpose The purpose of this study was to examine the morphological characteristics in patients with AFMR. Methods Among consecutive 795 patients undergoing initial radiofrequency catheter ablation (RFCA) at our hospital, twenty-five patients with persistent AF accompanied by AFMR (≥ moderate) before RFCA (AFMR group) were studied. Age-matched 25 patients with persistent AF without MR were defined as a control group. Results Left ventricular ejection fraction (LVEF) was lower and left atrium volume index was larger in the AFMR group (Table). Mitral valve annulus diameter and length of anterior mitral leaflet (AML) were similar between groups, whereas length of posterior mitral leaflet (PML) was significantly shorter in the AFMR group. Smaller tethering angle of AML (γ in the figure) and shorter tethering height were significantly associated with the occurrence of AFMR, which were different from morphology of functional mitral regurgitation in patients with dilated LV. Multiple regression analysis revealed that less tenting height (p<0.05) and LA dilatation toward the posterior (p<0.01) were significantly related to AFMR. Echocardiographic parameters AFMR (n=25) Control (n=25) P value Age, y 69±8 66±10 NS Male, n (%) 9 (36) 20 (80) P=0.001 LVEF,% 60±9 67±6 P=0.004 LAD, mm 44±5 41±7 NS LAVI, ml/m2 56±17 41±13 P<0.001 MV diameter, mm 3.9±0.4 3.8±0.5 NS α angle, ° 34±9 35±7 NS β angle, ° 48±9 50±8 NS γ angle, ° 32±5 37±5 P=0.0005 AML length, mm 3.0±0.5 3.0±0.5 NS PML length, mm 2.1±0.1 2.4±0.1 P=0.03 Tenting height, mm 1.5±0.1 1.8±0.1 P=0.02 D, mm 0.8±0.3 0.5±0.3 P=0.001 LVEF: left ventricular ejection fraction; LAD: left atrial diameter; LAVI: left atrial volume index; AML: anterior mitral leaflet; PML: posterior mitral leaftlet. Conclusions AFMR occurs in patients with unique morphological features, such as less tethering height and LA dilatation toward the posterior.

P4728Prognostic implications of the relationship between effective regurgitant orifice area and left ventricle end diastolic volume in patients with functional mitral regurgitation treated with MitraClip

Abstract Background The distinction between proportionate and disproportionate functional mitral regurgitation (FMR), based on the relationship between effective regurgitant orifice area (EROA) and left ventricle end diastolic volume (LVEDV), has recently been proposed as a possible new clinical and physiopathological concept to identify patients that could likely benefit from transcatheter mitral repair. Purpose The aim of our study was to explore the possible prognostic implications of the EROA/LVEDV ratio in patients with FMR treated with MitraClip. Methods Baseline EROA/LVEDV ratio was calculated in 72 patients with moderate-to-severe, symptomatic FMR treated with MitraClip. All patients underwent clinical, biochemichal and echocardiographic evaluation before MitraClip. EROA was calculated using PISA method. The primary outcome was a composite end-point of all-cause death or re-hospitalization for heart failure (HF). Results The median follow-up was 1 year. The primary outcome occurred in 25 patients (34.7%). The cut-off value of EROA/LVEDV ratio for primary outcome, identified by receiver operating characteristic curve, was 0.15 (p=0.007) with a sensitivity and specificity of 72 and 68%, respectively. Patients were divided in two groups according to the identified cut-off. Patients with higher ratio (Group I, n=35) presented a less dilated LV (LVEDVi: 113.2±33.4 mL vs 129.3±29.3 mL, p=0.033; LVESV: 140.7±49.0 mL vs 171.1±47.4 mL, p=0.010), a better LV systolic function (LVEF: 31.9±9.5% vs 27.8±5.8%, p=0.028) and a more severe MR (EROA: 44.5±12.9 mm2 vs 24.5±6.8 mm2, p<0.001; vena contracta: 7.4±1.5 mm vs 6.7±1.0 mm, p=0.045). Patients with lower ratio (Group II, n=37) showed a reduced prevalence of MV annular dilation (57.1% vs 91.7%, p=0.005) and a worse RV function (s'TDI: 9.2±2.2 cm/s vs 10.5±2.9 cm/s, p=0.039). At univariate analysis, EROA/LVEDV ratio >0.15 (HR = 2.467, 95% CI 1.017–5.982, p=0.046) and severe pulmonary hypertension (HR = 2.481, 95% CI 1.030–5.976, p=0.043) were associated with a worse clinical outcome. At multivariate Cox-regression analysis, both EROA/LVEDV ratio >0.15 and severe pulmonary hypertension were identified as independent predictors (HR 3.203, 95% CI 1–310–7.832, p=0.011; HR = 3.280, 95% CI 1.326–8.116, p=0.010, respectively). Figure 1 Conclusion Our data show that EROA/LVEDV ratio was an independent predictor of adverse clinical outcome in FMR patients treated with MitraClip. This preliminary experience shows that this index could help to identify subgroups of patients with potential different clinical benefits from MitraClip therapy. However, further and extended data are needed to provide more precise evidence. Acknowledgement/Funding None

P6491Predictive effect of mitral annular size on persistent mitral valve dysfunction after transcatheter edge-to-edge mitral valve repair for functional mitral regurgitation

Abstract Background In patients with functional mitral regurgitation (FMR), deformation of the mitral valve (MV) apparatus leads to deteriorating coaptation of both leaflets. The MV geometry is essential to predict procedural success of using the MitraClip™ for FMR patients. Persistent such mitral regurgitation (MR) and post-procedural mitral stenosis (MS) are parameters for an increasing mortality rate after MitraClip implantation. The anterior-to-posterior mitral annulus diameter (MAD) is simple to evaluate with a high reproducibility rate. However, the predictive effect has not been determined to date. Purpose We evaluated the predictive effect of baseline anterior-to-posterior MAD on persistent MV dysfunctions after MitraClip™ implantation. Methods We investigated the prevalence of procedural failure (MR at discharge > grade 2+) and post-procedural MS (mean transmitral gradient (mTMG) at discharge ≥6 mmHg) in a patient cohort with FMR (n=190), who underwent MitraClip™ implantation. We measured the MV apparatus geometry on mid-systole using transoesophageal echocardiography before the index procedure. The MAD was stratified by interquartile ranges (IQR) in the comparison. (≤34 mm, 35 to 37 mm, 38 to 40 mm, and ≥41 mm, respectively) Results The mean age was 75±9 years, and 63 patients (33%) were female. The mean left ventricular ejection fraction was 34±14%. Moderate-to-severe (3+) or severe MR (4+) were documented in all patients before the procedure. Transthoracic echocardiography at discharge revealed residual MR (>2+) in 10 patients (5%) and post-procedural MS in 13 patients (7%), in which one patient presented with both residual MR and MS. After stratification by the IQRs of MAD, there were significant differences in body weight (p<0.001), height (p<0.001), and body surface area (p<0.001), but no significant differences in the other baseline characteristics. Notably, significant differences in the prevalence of procedural failure (p=0.004) and post-procedural MS (p=0.022) were observed among the groups. (Figure) Specifically, in the cohort with the 4th IQR (MAD ≥41 mm, n=44), procedural failure was observed in 7 patients (16%), although the prevalence was only 2% in the other IQR groups. Moreover, the cohorts with the 1st and 2nd IQR presented with higher prevalence of post-procedural MS (6 of 46 patients (13%) in the 1st IQR group, and 6 of 51 (12%) in the 2nd IQR group) than those with the 3rd and 4th IQRs. (1 of 49 patients (2%) in the 3rd IQR, and none of 44 patients in the 4th IQR) Figure 1 Conclusion In this analysis we showed that the mitral annulus size affected MV dysfunction after MitraClip™. Anterior-to-posterior MAD was useful to predict the procedural result. For FMR candidates with dilated mitral annulus larger than 40 mm, new-generation MitraClip-XTR™ system or other therapeutic concept such as annuloplasty may be reasonable to obtain satisfactory MV function.

1384MitraClip treatment of functional mitral regurgitation - A meta-analysis

Abstract Moderate-to-severe or severe functional mitral regurgitation (FMR) is associated with higher rates of hospitalizations and with increased mortality in heart failure with reduced left ventricular ejection fraction (HFrEF). Transcatheter mitral valve repair by MitraClip® implantation (TMVrMC) may effectively reduce severe MR, and is associated with symptomatic improvement. However, the long-term clinical effects of this procedure are not well defined. Aims We analyzed outcomes for rehospitalization and survival in heart failure patients with moderate-to-severe or severe functional mitral regurgitation (FMR) treated by either medical treatment (MT) only TMVrMC+MT by meta-analysis. Methods and results By systematic search of bibliographic databases, we evaluated publications comparing heart failure patients with FMR treated by MT only versus treatment by MT combined with TMVrMC. Studies with a minimum of 25 enrolled patients and a follow/up period of at least 12 months were deemed eligible for this meta-analysis. We identified n=7 studies enrolling 2,884 HFrEF patients, divided into two study arms: TMVrMC+MT (n=1,618), versus FMR patients receiving MT only (n=1,266). At 12 months, there was a significant reduction in all-cause mortality favoring TMVR+MT (OR: 0.67; CI 95% 0.55–0.81), as well as a reduction of unplanned rehospitalizations (OR: 0.69; 95%; CI 0.53–0.89), compared with the MT only patients. At 24 months, there was a significant reduction of all-cause mortality in the TMVrMC+MT patient group (OR: 0.50; CI: 95%: 0.38–0.66; p<0.001). TMVrMC+MT was associated with significantly lower rates of unplanned re-admissions for heart failure compared with MT only at 12 months (OR: 0.69; 95% CI: 0.53–0.89; p<0.001) and at 24 months (OR: 0.53; 95% CI: 0.39–0.71; p<0.001). In one publication, a survival benefit of TMVrMC+MT over MT alone was shown at 5 years post intervention (HR: 0.75; 95% CI: 0.69–0.94; p=0.012) after weighting for propensity score and controlling for age. Conclusions This meta-analysis on n=2,884 patients with moderate-to-severe or severe FMR reveals that TMVrMC+MT, as compared with MT alone, is associated with a significant reduction of rehospitalizations and improvement of survival. These data imply additional evidence for TMVrMC in eligible heart failure patients with relevant FMR, which might be important for an update of the corresponding guidelines.

P4726Functional mitral regurgitation treated with percutaneous repair: a relative survival analysis of a national Swiss cohort

Abstract Introduction Percutaneous treatment of functional mitral regurgitation (FMR) with MitraClip (MC) has led to discordant results in recent randomized clinical trials. We aimed at estimating excess mortality (EM) and to evaluate its predictors in a large Swiss FMR population treated with MC. Methods FMR patients enrolled in the MitraSwiss Registry (479 pts) with a mean age of 74.7±9.42 years were evaluated. We computed and plotted EM up to 5 years after implant using the Swiss 2008–20013 mortality tables, stratified by age and sex. A Poisson regression was used to model EM as a function of age, sex, pre-implant RV/RA gradient, calendar period (2011–2013; 2014–2015,2016–2017), ischemic vs non ischemic aetiology, acute procedural success and residual MR. Results Patient's survival at 1,2,3,4 and 5 years were respectively 0.84, 0.72, 0.59, 0.53 and 0.48. FMR patients treated with MC showed excess mortality of +13% (95% CI,10%-18%), +22% (95% CI,17%-28%), +34% (95% CI,27%-41%), +37% (95% CI,28%-46%) and +39% (95% CI,28%-50%) at each time point as compared to the Swiss population, with not differences over the entire follow up (p=0.481). Age group, sex, RV/RA gradient calendar period, ischemic vs non ischemic and residual MR were not associated with excess mortality while a clear association was recognized with acute procedural success (p=0.011). Conclusions In FMR patients treated with MC a persistent EM was observed at a 5 years follow up. Acute procedural success is the only determinant of EM with a 65% lower EM as compared to procedural failures.

Functional Mitral Regurgitation and Congestive Heart Failure in Sickle Cell Anemia and Hemoglobin SC Disease

Introduction Anemia, a risk factor for cardiovascular disease, is associated with changes in left ventricle (LV) structure and physiology, namely LV dilation and hypertrophy. Patients with sickle cell anemia (HbSS) and hemoglobin SC disease (HbSC) exhibit similar changes in cardiac morphology and function. LV dilation increases the risk of functional mitral regurgitation (FMR), the abnormal mitral valve (MV) leaflet coaptation secondary to MV annulus dilation, resulting in valve insufficiency. FMR is associated with the development of congestive heart failure (CHF). Hypothesis HbSS and HbSC are associated with LV and additional cardiac chamber changes that increase the risk of FMR and CHF. Methods A retrospective, cross-sectional study was performed in adult patients with HbSS and HbSC. Clinical and hematologic data was obtained based on date of echocardiography. Perason chi-square analysis assessed differences in clinical, hematologic, and echocardiographic parameters in HbSS patients with and without FMR, and HbSC patients with and without FMR. Additional analysis assessed differences between HbSS patients with FMR and HbSC patients with FMR. Results Among HbSS patients (n=225), those with FMR (n=116) had a higher mean age (39.6, p=0.045) and rate of kidney disease (20.7% v. 9.2%, p=0.014) than those without FMR, and a higher rate of CHF (7.8% v 0.8%, p=0.009). HbSS patients with FMR had lower mean hemoglobin (Hgb) level (mean 7.61 g/dL, standard deviation [SD] 1.34, p=0.034), and higher mean tricuspid max velocity (TV max vel mean 232.97 cm/sec, SD 56.02, p=0.040) and pulmonary artery systolic pressure (PASP mean 32.039 mmHg, SD 14.15, p=0.013). Among patients with HbSC (n=82), those with FMR (n=27) had lower mean Hgb (mean 10.35, SD 1.29, p=0.006) than those without FMR, but no significant differences in rates of CHF or in structural or physiologic parameters were observed. Comparison of HbSS patients with FMR to HbSC patients with FMR showed no difference in rate of CHF. HbSS patients had lower Hgb level (mean 7.608, SD 1.44, p Conclusion In patients with HbSS and HbSC, differences in Hgb were seen in those with and without FMR, both within individual genotypes and across as well. The differences observed in cardiac morphology and physiology in HbSS and HbSC patients suggest that FMR can contribute to cardiac pathophysiology, pulmonary hypertension, and symptomatic CHF in patients with sickle hemoglobinopathies, and further stress the need for echocardiographic screening guidelines in sickle cell disease, both HbSS and HbSC.

Mitral annuloplasty for atrial functional mitral regurgitation in patients with chronic atrial fibrillation.

Surgical ring annuloplasty is generally performed in patients with symptomatic atrial functional mitral regurgitation (MR) caused by long-standing atrial fibrillation (AF). However, its clinical results have not been well reported. Twenty consecutive patients with atrial functional MR (mean age of 68 ± 9 years) and a left ventricular (LV) ejection fraction (EF) greater than 50% underwent mitral annuloplasty. Concomitant procedures included tricuspid valve surgery in 16 patients, AF ablation in 13 patients, and coronary artery bypass grafting in 2 patients. We reviewed the clinical outcomes of those patients and investigated the specific preoperative echocardiographic findings related to MR recurrence. At discharge, the mean left atrial (LA) volume index and mean tricuspid regurgitation peak gradient had significantly decreased from 94 ± 59 mL/m 2 to 58 ± 30 mL/m 2 and from 34 ± 11mm Hg to 23 ± 5mm Hg, respectively. During the follow-up period of 28 ± 17 months, the New York Heart Association functional class significantly improved from 2.3 ± 0.6 to 1.3 ± 0.6. Four patients developed recurrent MR, and of those, two required reoperation. Those with recurrent MR had a significantly larger preoperative LV dimension than those without recurrent MR. Preoperative three-dimensional transesophageal echocardiography was performed in 12 patients, revealing a greater degree of leaflet tethering in patients with recurrent MR than that in patients without recurrent MR. In patients with the combination of atrial functional MR, left ventricular dilatation and excessive leaflet tethering, mitral annuloplasty alone may not be sufficient to achieve long-term correction of MR.

Prognostic impact of MitraClip in patients with left ventricular dysfunction and functional mitral valve regurgitation: A comprehensive meta-analysis of RCTs and adjusted observational studies

The real prognostic impact of MitraClip in patients with significant functional mitral regurgitation (FMR) and left ventricular (LV) dysfunction remains to be elucidated. Two randomized controlled trials (RCTs) with conflicting results have been recently published.We conducted a comprehensive meta-analysis of all RCTs and adjusted observational studies to evaluate the clinical impact of percutaneous mitral valve repair when compared with optimal medical therapy (OMT) alone, in patients with symptomatic FMR and LV dysfunction. Death from any cause and heart failure rehospitalizations at the longest available follow-up were the primary endpoints. Cardiac death, one year and short-term death were the secondary ones. 2255 patients (1207 for MitraClip and 1048 for OMT-only) from 8 studies (2 RCTs and 6 observational studies) were included. At a median (mid-term) follow-up of 438 days (IQR 360–625) MitraClip was associated with a significant reduction of all-cause death (odds Ratio [OR] 0.55, 95%CI 0.41–0.73, p < 0.001; [ORadj] 0.66, 95%CI 0.49–0.90, p = 0.009) and rehospitalization (OR 0.49, 95%CI 0.24–1.00, p = 0.05 and ORadj 0.63, 95%CI 0.43–0.94, p = 0.02). At one year, adjusted analysis demonstrated a trend favoring the experimental cohort (ORadj 0.73, 95%CI 0.53–1.02, p = 0.07). Meta-regression suggested that benefit of MitraClip on mid-term survival persists even after accounting for the prevalence of implanted CRT, burden of comorbidities, NYHA class, cardiomyopathy etiology and LV function and dimensions. In conclusion, MitraClip for FMR in patients with LV dysfunction is associated with a considerable reduction of death and HF hospitalization at mid-term follow-up. Further ongoing RCTs are needed to strengthen present results.

Predictive impact of previous coronary artery bypass grafting on mortality after MitraClip implantation for ischemic functional mitral regurgitation

BackgroundMany candidates with ischaemic functional mitral regurgitation (FMR) have previously undergone coronary artery bypass grafting (CABG), in which transcatheter mitral valve repair can be reasonable for ameliorating the deteriorated hemodynamic and heart failure symptoms. We sought to elucidate the outcomes of MitraClip (MC) implantation in patients with symptomatic ischaemic FMR after CABG. MethodsWe investigated clinical characteristics, outcomes and predictive impact of previous CABG on mortality in ischaemic FMR patients who underwent MC implantation from two high-volume centres in Germany. ResultsWe enrolled 159 patients who previously underwent CABG. Compared with a reference group that did not previously undergo CABG (n = 182), the cohort consisted of more elderly patients (75.0, standard deviation [SD] 7.7 versus 72.9, SD 9.6 years, p = 0.028), more men (84% vs. 69%, p < 0.001), and reduced tricuspid annular plane systolic excursion (14.0, SD 4.0, vs. 16.6, SD 4.6 mm, p < 0.0001). The CABG group showed similar outcomes regarding procedural success (91% vs. 94%, p = 0.24) and 30-day mortality (5.0% vs. 6.0%, p = 0.68), but worse survival after MC implantation (log-rank p = 0.019, hazard ratio 1.56 [95% confidence interval (CI) 1.08–2.26]). After propensity score matching (n = 224), the hazard ratio was 1.18 [95%CI 0.76–1.84] without statistical significance (p = 0.46). ConclusionsTranscatheter mitral valve repair using the MC is a viable treatment option for patients with symptomatic ischaemic FMR after CABG. Although the baseline characteristics seemed to point to sick patients, CABG itself had only a modest impact on survival.

Mid-term outcomes (up to 5 years) of percutaneous edge-to-edge mitral repair in the real-world according to regurgitation mechanism: A single-center experience.

To report mid-term results after MitraClip repair, according to mitral regurgitation (MR) mechanism, in a real-world single-center experience. Mid-term outcomes of percutaneous edge-to-edge mitral repair in the real world are still limited. We assessed the follow-up results of patients treated with MitraClip at a single high-volume mitral center from 2008 to 2016. All patients underwent Heart-Team discussion, prospective data collection and enrolment in a dedicated outpatient clinic. Functional (FMR, n = 242, 68.6%) and degenerative (DMR, n = 97, 27.5%) MR patients were separately analyzed. 5-Year survival was 53.5 ± 4.5% in FMR vs 57.1 ± 7.5% in DMR (P = 0.087). Reduced survival was strongly associated with worse left ventricle remodeling (ESV HR 1.01, CI 1.01-1.02, P < 0.001) in FMR, and with worse symptoms (New York Heart Association IV HR 6.72, CI 1.78-25.45, P = 0.005) in DMR. 5-Year cumulative incidence function for MR ≥ 3 was 23.7 ± 3.4% in FMR vs 27.9 ± 5.9% in DMR (P = 0.39), being associated with residual MR = 2 both in FMR (HR 4.67, CI 2.49-8.74, P < 0.001) and DMR (HR 7.15, CI 2.72-18.75, P < 0.001). At 5-year, patients in NYHA class I-II increased from 17.9% to 45.3% in FMR (P < 0.001) and from 33.3% to 51.3% in DMR (P < 0.001). In this single-center real-world experience, 5-year after MitraClip, half of the patients were alive and 3/4 were free from MR, both in FMR and DMR. Symptoms benefit was sustained in both groups. Advanced ventricular remodeling, advanced symptoms, and suboptimal MR reduction were associated with worse results. Refined patient selection, improved efficacy and more data will be all required to improve long-term outcomes.

Informed decision-making in patients with valvular disease.

A number of papers published in 2018 have provided important information expected to influence clinical practice, particularly for the management of functional mitral regurgitation in patients with heart failure caused by ischaemic or non-ischaemic cardiomyopathy and for the treatment of severe aortic stenosis in patients at low surgical risk.

Abstract 16759: Repair of Functional Mitral Regurgitation Restores Life Expectancy in Selected Patients Less Than 70 Years of Age

Introduction: Functional mitral regurgitation (MR) is common and associated with significant morbidity and mortality. Notably, correction of functional MR has not been demonstrated to improve survival. We therefore evaluated outcomes following repair of functional MR utilizing prospective population data. Hypothesis: We hypothesized that correction of functional MR may be associated with a survival benefit in selected patients. Methods: Between 2001 and 2018, 1896 patients underwent complex mitral surgery at our institution, of which 168 underwent repair of functional MR in whom the etiology of MR was due to annular dilation in 37, leaflet tethering in 100 and mixed in 31. Mean patient age was 66.2±9.9 years and 66 (39%) were female. Concomitant coronary artery bypass grafting was performed in 79 (47%) with an average of 2.5 grafts per patient. The mean preoperative left ventricle (LV) ejection fraction was 38.3±11.4% and indexed LV end-systolic dimension, 25.1±5.4 mm/m 2 . Average clinical and echocardiographic follow up averaged 5.5±3.8 years. Results: Thirty-day mortality was 0.6%. Overall survival for the patients following repair of functional MR was 93.3±2.0% and 75.6±3.8% 1-, and 5-years after surgery. Not surprisingly, sensitivity analysis demonstrated that survival was influenced by age at operation (hazard ratio (HR) 1.05±0.02 per increasing year) and preoperative left ventricle (LV) class (HR 1.32±0.18 per increasing LV grade) (Both p&lt;0.05). For patients &lt;70 years of age and with a preoperative LVEF &gt;35%, 5- year survival was 92.3±7.4%, respectively. This compares to an expected 5- year survival of 99.1%, for age and gender matched Canadians (Figure). For patients &lt;70 and with a preoperative LVEF &gt;35%, 5-year freedom from recurrent MR ≥2+ was 81.3±9.8%. Conclusions: Repair of functional MR is associated with favorable early and intermediate term results in selected patients. Notably, for the subset of functional MR patients &lt;70 and with a LVEF&gt;35%, 5-year survival was comparable to age and gender matched patients from the general population.

Predictors of outcome in heart failure patients with severe functional mitral regurgitation undergoing MitraClip treatment

BackgroundThe prognostic predictors of outcome in patients with functional mitral regurgitation (FMR) undergoing MitraClip implantation (MCi) are still poorly known. The aim of our study is to identify the baseline predictors of outcome in FMR patients candidate to MCi. MethodsAll patients with symptomatic moderate-to-severe or severe FMR undergoing MCi at our institution were consecutively and prospectively enrolled. Baseline clinical and instrumental data were collected. Primary endpoint was the occurrence of cardiac death; secondary endpoints were all-cause death and the composite of cardiac death or rehospitalization for heart failure. Results74 patients (mean 71.6 ± 8.3 years) were enrolled. During follow-up (median 416.0 days), the primary endpoint occurred in 15 (20.3%), all-cause death in 26 (35.1%) and the composite endpoint in 25 (33.8%). At multivariate analysis, the left atrial volume index (LAVi; HR:1.02; P = 0.048) and the low peak oxygen uptake (peak VO2; HR:0.73; P = 0.018) increased the risk of cardiac death at follow-up; atrial fibrillation (AF; HR:2.69; P = 0.027) was independently associated to all-cause death and the low level of peak VO2 was an independent predictor of overall mortality (HR:0.70; P < 0.001) as well as of the composite endpoint (HR:0.73; P < 0.001).The ROC analysis identified a peak VO2 cut-off of 10.0 mL/kg/min as the best predictor for the three study endpoints; the best LAVi cut-off for cardiac death was 67 mL/m2. Kaplan-Meier analysis for the individual and combined outcome predictors confirmed their significant stratification ability during follow-up. ConclusionsPeak VO2, along with LAVi and AF, identify FMR patients with the worst prognosis after MCi.

Transcatheter Repair of Functional Mitral Regurgitation in Heart Failure Patients - A Meta-Analysis of 23 Studies on MitraClip Implantation.

The aim of this study was to investigate long-term survival, clinical status, and echocardiographic findings of patients with severe functional mitral regurgitation (FMR) undergoing MitraClip (MC) treatment and to explore the role of baseline features on outcome. Methods and Results: Randomized and observational studies of FMR patients undergoing MC treatment were collected to evaluate the overall survival, New York Heart Association (NYHA) class and echocardiographic changes after MC treatment. Baseline parameters associated with mortality and echocardiographic changes were also investigated. Across 23 studies enrolling 3,253 patients, the inhospital death rate was 2.31%, whereas the mortality rate was 5.37% at 1 month, 11.87% at 6 months, 18.47% at 1 year and 31.08% at 2 years. Mitral regurgitation Grade <3+ was observed in 92.76% patients at discharge and in 83.36% patients at follow-up. At follow-up, 76.63% of patients NYHA Class I-II and there were significant improvements in left ventricular (LV) volume, ejection fraction, and pulmonary pressure. Atrial fibrillation (AF) had a significant negative effect on 1-year survival (β=0.18±0.06; P=0.0047) and on the reduction in LV end-diastolic and end-systolic volumes (β=-1.05±0.47 [P=0.0248] and β=-2.60±0.53 [P=0.0024], respectively). MC results in durable reductions in mitral regurgitation associated with significant clinical and echocardiographic improvements in heart failure patients. AF negatively affects LV reverse remodeling and 1-year survival after MC treatment.

Short-term and 1-year outcomes after MitraClip therapy in functional versus degenerative mitral regurgitation patients: a systematic review and meta-analysis.

Differences in short-term and 1-year outcomes of percutaneous edge-to-edge mitral repair between patients with functional and degenerative mitral regurgitation (MR) remain unclear. We performed a systematic review and meta-analysis to investigate the safety and efficacy of MitraClip (MC) in patients with different MR etiologies. This study systematically searched three common databases for studies on MC therapy until November 2017. The studies meeting the standard inclusion criteria were included. The data at baseline, short-term and 1-year clinical and echocardiographic outcomes were obtained and analyzed. All data were checked by another reviewer. Thirteen studies totalling 2,351 patients investigating the short-term and 1-year outcomes of MC in patients with functional MR (FMR) versus degenerative MR (DMR) were included for further analysis. FMR patients presented a higher risk profile at baseline. There was no difference in short-term outcomes between DMR and FMR for post-procedural MR grade 0-2 (76.8% vs. 77.1%; P=0.428), mean trans-mitral gradient (3.92 vs. 3.50 mmHg; P=0.098), 30-day mortality rate (0.05% vs. 0.03%; P=0.118) and 30-day NYHA I-II (85.3% vs. 78.7%; P=0.211). FMR patients had a higher rate of acute procedural success compared to the DMR patient group (91.2% vs. 95.2%; P=0.016). A greater portion of DMR patients implanted two or more MCs than the FMR patients (41.4% vs. 35.7%; P=0.043). For the 1-year outcomes, no difference was found in the mortality rate (13.0% vs. 15.2%; P=0.268) and proportion of patients with post-procedural MR grades 0-2 (75.0% vs. 80.7%; P=0.106). Despite a higher risk profile in FMR patients, the short-term and 1-year outcomes were not significantly different. We conclude that MC therapy is similar between FMR and DMR patients until 1-year follow-up. Large randomized trials are warranted to fully and further assess the clinical impact of the procedure in these two MR etiologies over a longer period of time.

Finite element analysis of annuloplasty and papillary muscle relocation on a patient-specific mitral regurgitation model.

ObjectivesFunctional mitral regurgitation (FMR) is a significant complication of left ventricle (LV) dysfunction associated with poor prognosis and commonly treated by undersized ring annuloplasty. This study aimed to quantitatively simulate the treatment outcomes and mitral valve (MV) biomechanics following ring annulopalsty and papillary muscle relocation (PMR) procedures for a FMR patient.MethodsWe utilized a validated finite element model of the left heart for a patient with severe FMR and LV dilation from our previous study and simulated virtual ring annuloplasty procedures with various sizes of Edwards Classic and GeoForm annuloplasty rings. The model included detailed geometries of the left ventricle, mitral valve, and chordae tendineae, and incorporated age- and gender- matched nonlinear, anisotropic hyperelastic tissue material properties, and simulated chordal tethering at diastole due to LV dilation.ResultsRing annuloplasty with either the Classic or GeoForm ring improved leaflet coaptation and increased the total leaflet closing force while increased posterior mitral leaflet (PML) stresses and strains. Classic rings resulted in larger coaptation forces and areas compared to GeoForm rings. The PMR procedure further improved the leaflet coaptation, decreased the PML stress and strain for both ring shapes and all sizes in this patient model.ConclusionsThis study demonstrated that a rigorously developed patient-specific computational model can provide useful insights into annuloplasty repair techniques for the treatment of FMR patients and could potentially serve as a tool to assist in pre-operative planning for MV repair surgical or interventional procedures.