A Novel Presentation of Eclipsed Mitral Regurgitation.

Eclipsed mitral regurgitation (MR) is a rare phenomenon of transient severe MR in patients with normal left ventricular function. This paper presents a case of a patient with recurrent heart failure exacerbations and transient, positional severe MR consistent with eclipsed MR, which improved after mitral transcatheter edge-to-edge repair.

Paroxysmal Mitral Regurgitation Treated by Edge-to-Edge Repair.

A 76-year-old woman with a history of recurrent pulmonary edema was referred because of sudden worsening of dyspnea and cardiogenic shock. Eclipsed mitral regurgitation was identified as the cause. We applied hand-grip stress echocardiography in diagnosis and therapeutic evaluation and managed her condition by transcatheter edge-to-edge mitral valve repair.

Recovery of left ventricular function after surgery for aortic and mitral regurgitation with heart failure.

Background: Severe aortic regurgitation (AR) and mitral regurgitation (MR) can lead to left ventricular (LV) systolic dysfunction; however, there are limited data about recovery of LV after surgery for AR or MR. Little is known to guide the management of combined AR and MR (mixed valvular heart disease [VHD]). This study is sought to investigate the predictors of postoperative LV function recovery in left-sided regurgitant VHD with reduced left ventricular ejection fraction (LVEF), especially for mixed VHD. Methods: From 2010 to 2020, 2053 adult patients underwent aortic or mitral valve surgery at our center. The patients with valvular stenosis, infective endocarditis, concomitant revascularization, and preoperative LVEF ≥40 % were excluded. A total of 127 patients were included in this study: 22 patients with predominant AR (AR group), 64 with predominant MR (MR group), and 41 with combined AR and MR (AMR group). Results: The mean preoperative LVEF was 32.4 %, 30.7 %, and 30.2 % (p = 0.44) in the AR, MR, and AMR groups, respectively. The AR group was more likely to have postoperative LVEF recovery. The cut-point of left ventricular end-systolic diameter (LVESD) for better recovery was 49 mm for the MR group and 58 mm for the AMR group. Conclusion: LV dysfunction due to combined AR and MR has similar remodeling reserve as AR, and better recoverability than MR. Thus, double-valve surgery is recommended before the LVESD is > 58 mm.

Characterisation of global and regional mitral annular strains in an acute porcine model.

OBJECTIVES: This study aimed to explore regional mitral annular strain using a novel computational method. METHODS: Eight pigs underwent implantation with piezoelectric transducers around the mitral annulus. Interventions of pre- and afterload were performed by inferior vena cava constriction and endovascular balloon occlusion of the descending aorta. The mitral annulus was reconstructed in a mathematical model and divided into 6 segments. Global and segmental annular strain were calculated from a discrete mathematical representation. RESULTS: Global annular strain gradually decreased after isovolumetric contraction until late systole. Mitral annular end-systolic strain demonstrated shortening in all segments except the anterior segment, which showed the least deformation. The P2 annular segment demonstrated the most end-systolic shortening (-7.6 ± 1.1% at baseline, P < 0.001 compared to anterior segment). Systolic global annular strain showed no significant change in response to load interventions but correlated positively with left ventricular contractility at baseline and after preload reduction. CONCLUSIONS: Mitral annular systolic strain demonstrates cyclical variations with considerable regional heterogeneity, with the most pronounced deformation in posterior annular segments. Measurements appear independent of changes to pre- and afterload.

Prognostic Value of Echocardiographic-derived Stroke Volume in Severe Primary Mitral Regurgitation.

AIM: Studies have demonstrated the importance of forward flow, and specifically of stroke volume (SV) and SV index (SVI), as prognostic markers in different cardiovascular diseases. Here we aimed to evaluate the association between SV and SVI thresholds and prognosis in patients with severe primary mitral regurgitation (MR). METHODS AND RESULTS: The association between either SV (<55, 55-70 and >70ml) or SVI (<30, 30-35 and >35mL/m²) thresholds and all-cause mortality and heart failure (HF) hospitalizations was examined in a retrospective analysis of 283 patients (60% male, median age 70 years, IQR 58-82) with severe primary MR, normal left ventricular size and systolic function and no other significant left-sided valvular abnormalities. Compared with normal values, SV<55ml was found to be associated with worse outcomes (HR 1.8, IQR 1.1-2.8, P=0.016), whereas SV between 55-70ml was not. A non-significant trend for worse outcomes was noted for SVI<35ml/m² compared with normal SVI. CONCLUSION: In patients with severe primary MR, SV<55ml was found to be associated with increased rates of HF hospitalization and all-cause mortality. This easily obtainable parameter may allow for better risk stratification of patients with primary MR.

Quantitation of mitral regurgitation using positron emission tomography.

BACKGROUND: Cardiac positron emission tomography (PET) offers non-invasive assessment of perfusion and left ventricular (LV) function from a single dynamic scan. However, no prior assessment of mitral regurgitation severity by PET has been presented. Application of indicator dilution techniques and gated image analyses to PET data enables calculation of forward stroke volume and total LV stroke volume. We aimed to evaluate a combination of these methods for measurement of regurgitant volume (RegVol) and fraction (RegF) using dynamic 15O-water and 11C-acetate PET in comparison to cardiovascular magnetic resonance (CMR). RESULTS: Twenty-one patients with severe primary mitral valve regurgitation underwent same-day dynamic PET examinations (15O-water and 11C-acetate) and CMR. PET data were reconstructed into dynamic series with short time frames during the first pass, gated 15O-water blood pool images, and gated 11C-acetate myocardial uptake images. PET-based RegVol and RegF correlated strongly with CMR (RegVol: 15O-water r = 0.94, 11C-acetate r = 0.91 and RegF: 15O-water r = 0.88, 11C-acetate r = 0.84, p < 0.001). A systematic underestimation (bias) was found for PET (RegVol: 15O-water - 11 ± 13 mL, p = 0.002, 11C-acetate - 28 ± 16 mL, p < 0.001 and RegF: 15O-water - 4 ± 6%, p = 0.01, 11C-acetate - 10 ± 7%, p < 0.001). PET measurements in patients were compared to healthy volunteers (n = 18). Mean RegVol and RegF was significantly lower in healthy volunteers compared to patients for both tracers. The accuracy of diagnosing moderately elevated regurgitant volume (> 30mL) was 95% for 15O-water and 92% for 11C-acetate. CONCLUSIONS: LV regurgitation severity quantified using cardiac PET correlated with CMR and showed high accuracy for discriminating patients from healthy volunteers.

Atrial Functional Mitral Regurgitation: From Diagnosis to Current Interventional Therapies.

Mitral regurgitation (MR) is one of the most common valvular pathologies worldwide, contributing to the morbidity and mortality of several cardiovascular pathologies, including heart failure (HF). Novel transcatheter treatment for MR has given the opportunity for a safe and feasible alternative, to surgery, in order to repair the valve and improve patient outcomes. However, after the results of early transcatheter edge-to-edge repair (TEER) trials, it has become evident that subcategorizing the mitral regurgitation etiology and the left ventricular function, in patients due to undergo TEER, is of the essence, in order to predict responsiveness to treatment and select the most appropriate patient phenotype. Thus, a novel MR phenotype, atrial functional MR (AFMR), has been recently recognized as a distinct pathophysiological entity, where the etiology of the regurgitation is secondary to annular dilatation, in a diseased left atrium, with preserved left ventricular function. Recent studies have evaluated and compared the outcomes of TEER in AFMR with ventricular functional MR (VFMR), with the results favoring the AFMR. In specific, TEER in this patient substrate has better echocardiographic and long-term outcomes. Thus, our review will provide a comprehensive pathogenesis and mechanistic overview of AFMR, insights into the echocardiographic approach of such patients and pre-procedural planning, discuss the most recent clinical trials and their implications for future treatment directions, as well as highlight future frontiers of research in the setting of TEER and transcatheter mitral valve replacement (TMVR) in AFMR patients.

The Role of Global Longitudinal Strain in the Follow-Up of Asymptomatic Patients with Chronic Primary Mitral Regurgitation.

Background/Objectives: In patients with chronic primary mitral regurgitation (MR), postoperative persistent left ventricular (LV) dysfunction underlines the lack of a sensitive parameter that can identify subclinical LV dysfunction and optimize the timing of intervention. Left ventricular global longitudinal strain (LV-GLS) is a measure of the longitudinal left ventricular systolic function, with prognostic significance. Its role in the follow-up of asymptomatic patients with MR is, however, poorly defined. The aim of this study was to assess the relative changes in LV-GLS in a cohort of MR patients and to correlate these changes with the need for intervention during a follow-up period. Methods: We conducted a prospective study on a cohort of 218 patients, divided into three subgroups according to MR severity (mild, moderate, severe). LV-GLS was measured at baseline and every six months during a median follow-up period of 30 months. The composite endpoint was the occurrence of heart failure symptoms, hospitalization for heart failure, LVEF < 60%, LVEDD > 45 mm, new onset atrial fibrillation, or cardiovascular death. Results: Patients with moderate and severe MR had a significantly lower GLS at baseline than those with mild MR (19.5% and 19.1% versus 22.3%, p < 0.01) despite a normal LVEF in all subgroups. The relative decrease in LV-GLS occurred earlier (at 12 months vs. 24 months) and was more evident in patients with moderate and severe MR (13.6% and 14.5%, respectively) versus patients with mild MR (6.72%). The baseline LV-GLS being under 18% and a relative decrease of over 10% in GLS were independent predictors of a composite outcome (HR = 1.59, CI 95% 1.17-2.86; HR = 1.74, CI 95% 1.2-2.91, p < 0.01). Conclusions: LV-GLS is a valuable monitoring tool for asymptomatic MR patients, a relative decrease > 10% in GLS may be predictive for the need for valve intervention.

Evaluating Mitral TEER in the Management of Moderate Secondary Mitral Regurgitation Among Heart Failure Patients.

BACKGROUND: Moderate secondary mitral regurgitation (SMR) represents a subgroup of heart failure (HF) patients with treatment restricted to medical therapy. Outcomes in patients with moderate SMR treated with mitral transcatheter edge-to-edge repair (M-TEER) are less well known. OBJECTIVES: The aim of this study was to assess the safety and effectiveness of M-TEER in subjects with moderate SMR using the EXPANDed studies. METHODS: One-year outcomes in subjects from the EXPANDed studies (EXPAND [A Contemporary, Prospective Study Evaluating Real-world Experience of Performance and Safety for the Next Generation of MitraClip Devices] and EXPAND G4 [A Post-Market Study Assessment of the Safety and Performance of the MitraClip G4 System] MitraClip studies) with baseline moderate SMR (2+), per echocardiographic core laboratory (ECL) assessment, were compared with subjects with baseline severe SMR (≥3+). RESULTS: There were 335 subjects with moderate SMR and 525 with severe SMR at baseline per ECL review. Baseline characteristics were similar between the 2 subgroups. After treatment with M-TEER, significant MR reduction was achieved in both groups. Significant left ventricular (LV) reverse remodeling was observed through 1 year, with a >20 mL decrease in LV end-diastolic and end-systolic volumes on average in the moderate SMR group. Significant 1-year improvements in NYHA functional class (>78% NYHA functional class I or II) and quality of life (>20 points on the Kansas City Cardiomyopathy Questionnaire-Overall Summary) were observed in subjects with moderate SMR. Similarly, low rates of major adverse events, all-cause mortality, and HF hospitalizations were observed between the 2 subgroups through 1 year. CONCLUSIONS: In the EXPANDed studies, subjects with moderate SMR treated with M-TEER had improvements similar to subjects with severe SMR in quality of life and positive LV remodeling at 1 year. Future studies are needed to evaluate if M-TEER would be beneficial for HF patients with moderate SMR.

Prognosis and predictors of right ventricular dysfunction by quantitative cardiac magnetic resonance in non-ischaemic cardiomyopathy.

AIMS: Pathophysiology and prognostic implications of right ventricle (RV) dysfunction in heart failure are complex and incompletely elucidated. Cardiac magnetic resonance imaging (CMR) is the reference standard for RV quantification, but its clinical implications in non-ischaemic cardiomyopathy (NICM), in the context of myocardial fibrosis and functional mitral regurgitation are not well defined. We evaluated predictors, prognostic impact, and thresholds for defining significant RV dysfunction in NICM. METHODS AND RESULTS: NICM patients (n = 624) undergoing CMR assessment during 2002-2017 were retrospectively studied. CMR's quantification of right ventricular ejection fraction (RVEF) was evaluated against the primary outcome of all-cause mortality, heart transplant, and/or left ventricular assist device implantation in threshold and multivariable analyses. Mean RVEF was 43 ± 13%, and factors associated with reduced RVEF were male sex, New York Heart Association (NYHA) class III-IV, right bundle branch block, lower left ventricular ejection fraction, higher mitral regurgitant fraction (MR-RF) and right ventricle size in NICM. RVEF per 5% increase was independently associated with the primary endpoint hazards ratio (95% confidence interval) 0.80 (0.73-0.88), P < 0.001. RVEF ≤40% was the optimal threshold associated with worse prognosis, regardless of late gadolinium enhancement (LGE) or MR-RF quantification. On the other hand, higher LGE was associated with primary endpoint in patients with RVEF ≤40% only, while risk associated with MR-RF was significant dampened after adjusting for RVEF. CONCLUSION: RVEF provides powerful risk stratification, with RVEF ≤40% defining significant RV dysfunction associated with adverse outcomes in NICM. The integration of quantitative CMR measurements for RVEF, LGE, and MR-RF provides comprehensive NICM risk prognostication.

Mismatch Between Residual Mitral Regurgitation and Left Atrial Pressure Predicts Prognosis After Transcatheter Edge-to-Edge Repair.

BACKGROUND: The mechanism and impact of mismatch between residual mitral regurgitation (MR) and postprocedural left atrial pressure (LAP) after transcatheter edge-to-edge repair (TEER), which may adversely affect clinical outcome, is of great interest. OBJECTIVES: This study aimed to examine the effect of hemodynamic mismatch after TEER on clinical outcomes in patients with heart failure due to severe MR and investigate the predictive factors for the mismatch using a prospective multicenter registry. METHODS: We categorized 1,477 patients into optimal (residual MR grade ≤1 and postprocedural LAP ≤15 mm Hg), mismatched (residual MR grade >1 or postprocedural LAP >15 mm Hg), and poor (residual MR grade >1 and postprocedural LAP >15 mm Hg) groups and examined their prognosis. The primary endpoint was a composite of all-cause mortality and heart failure hospitalization. RESULTS: There were 927 (62.7%), 459 (31.1%), and 91 (6.2%) patients categorized into optimal, mismatched, and poor groups, respectively. Cox regression analysis, referenced to the optimal group, revealed that the mismatched and poor groups exhibited a higher risk for the primary endpoint (HR: 1.55; 95% CI: 1.28-1.88; and HR: 1.95; 95% CI: 1.38-2.74, respectively). Six risk factors were identified as predictors of hemodynamic mismatch after TEER: body mass index, baseline left atrial volume index, atrial fibrillation, tricuspid annular plane systolic excursion value, preprocedural mean left atrial pressure, and postprocedural mean mitral valve pressure gradient. CONCLUSIONS: Post-TEER hemodynamic mismatch between residual MR and postprocedural LAP was associated with a poor prognosis. Six readily accessible perioperative parameters predict the hemodynamic mismatch. (OCEAN-Mitral registry; UMIN000023653).

Impact of residual mitral regurgitation after transcatheter edge-to-edge repair in atrial functional mitral regurgitation: Results from MITRA-PRO registry.

BACKGROUND: Transcatheter edge-to-edge repair (TEER) has emerged to address symptomatic atrial functional mitral regurgitation (aFMR) in patients who are at high operative risk. AIMS: No clinical data is available on the impact of residual mitral regurgitation (MR) following TEER in aFMR compared to ventricular functional MR (vFMR). METHODS: In the MITRA-PRO registry, 846 patients with FMR and MitraScore assessment for residual MR quantification were included (722 patients with vFMR and 124 patients with aFMR). RESULTS: Compared to vFMR similar procedural results in regard of residual MR following TEER were found in aFMR patients (MitraScore post TEER 2.5 ± 1.8 vs. 2.7 ± 1.9), while the amount of implanted TEER devices was increased in vFMR. 1-year survival was better in aFMR compared to vFMR regardless of relevant residual MR (MitraScore ≥ 4), while 1-year rehospitalization was comparable for both MR entities. Patients with aFMR and mild residual MR had a lower mortality rate (6.6% vs. 10.3%) and rehospitalization rate (29.1% vs. 46.2%) 1 year after mitral TEER. However, in contrast to vFMR a MitraScore ≥4 was no independent predictor of mortality in aFMR indicating a better tolerance toward residual MR. CONCLUSIONS: Residual MR is an independent predictor of 1-year mortality in vFMR patients, whereas in aFMR patients, a MitraScore of ≥4 is associated with higher mortality but is not an independent predictor in multivariate analysis. Therefore, minimizing MR through mitral TEER is crucial for survival in vFMR patients, while aFMR patients tolerate significant residual MR better 1 year after the procedure.

Pulmonary Vein Systolic Flow Reversal and Outcomes in Patients From the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) Trial.

Background: The implications of pulmonary vein (PV) flow patterns in patients with heart failure (HF) and mitral regurgitation (MR) are uncertain. We examined PV flow patterns in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) trial (NCT01626079), in which patients with HF and moderate-to-severe or severe functional MR were randomized to transcatheter edge-to-edge repair (TEER) with the MitraClip device plus guideline-directed medical therapy (GDMT) vs. GDMT alone. We sought to evaluate the prognostic utility of baseline PV systolic flow reversal (PVSFR) in HF patients with severe MR and to determine whether the presence of PVSFR can discriminate patients most likely to benefit from TEER in COAPT trial patients. Methods: Patients were categorized by the echocardiographic core laboratory-assessed baseline presence of PVSFR. Two-year outcomes were examined according to PVSFR and treatment. Results: Baseline PV flow patterns were evaluable in 526/614(85.7%) patients, 48.9% of whom had PVSFR. Patients with PVSFR had more severe MR, reduced stroke volume and cardiac output, greater right ventricular dysfunction, and worse hemodynamics. By multivariable analysis, PVSFR was not an independent predictor of 2-year all-cause death, or heart failure hospitalization (HFH). The reductions in the 2-year rates of all-cause death and HFH with TEER compared with GDMT alone were similar in patients with and without PVSFR (Pinteraction = 0.40 and 0.12, respectively). The effect of TEER on improving Kansas City Cardiomyopathy Questionnaire scores and 6-minute walk distance were also independent of PVSFR. Conclusions: In the COAPT trial, PVSFR identified HF patients with severe MR and more advanced heart disease. Patients with and without PVSFR had consistent reductions in mortality, HFH, and improved quality-of-life and functional capacity after TEER. Clinical Trial Registration: ClinicalTrial.gov IdentifierNCT01626079.

Implications of Myocardial Strain in Primary Mitral Regurgitation - A Cardiovascular Magnetic Resonance Study.

AIMS: Chronic primary mitral regurgitation (MR) results in progressive left ventricular (LV) remodeling. Abnormal myocardial deformation (strain) can be present despite preserved ejection fraction. Cardiovascular magnetic resonance (CMR) feature-tracking techniques allow assessment of global longitudinal strain (GLS) from routine cine-images. The aim of this study was to evaluate the prognostic value of CMR feature-tracking derived GLS in patients with primary MR. METHODS AND RESULTS: Consecutive patients undergoing CMR for chronic MR from January 2012 to June 2018 were enrolled. Patient with LV ejection fraction <50% were excluded. The composite primary outcome aiming to detect decompensation related to MR comprised of 1) referral for mitral surgery due to symptoms or LV systolic dysfunction or 2) cardiovascular death. The secondary outcome was all-cause death. A total of 422 patients were followed for a median of 2.7 years, the primary endpoint was met in 93 patients (34 patients reported symptoms at baseline). On multivariable analysis, GLS≥ -16.6% was associated with primary outcome (hazard ratio 1.90,p=0.01). In moderate MR cohort, patient with GLS≥ -16.6% had worse event-free survival while no significant different in mild or severe MR groups. GLS≥ -16.0% remained associated with all-cause death after adjusting for other covariates including the MR severity (hazard ratio 2.24,p=0.02). CONCLUSIONS: In primary MR patients with preserved systolic function, GLS was associated with our composite outcomes and all-cause death. GLS may serve as a marker of cardiac dysfunction in primary MR patients with preserved systolic function allowing identification of patients likely to decompensate during observation.

Impact of systolic dominant pulmonary venous flow morphology on outcomes after mitral transcatheter edge-to-edge repair.

BACKGROUND: The prognostic significance of intraprocedural pulsed-wave Doppler analysis of pulmonary venous flow (PVF) during mitral transcatheter edge-to-edge repair (TEER) remains understudied. We aimed to investigate the prognostic value of systolic dominant-PVF (SD-PVF) morphology post-TEER. METHODS: In a retrospective analysis from December 2019 to December 2022, patients undergoing mitral TEER were categorized into SD-PVF and systolic blunting (SB)-PVF groups based on post-TEER morphology. The primary endpoint was a composite of all-cause mortality or heart failure hospitalization at 1 year. We investigated the association of PVF morphology post-TEER with the primary endpoint at 1 year using Cox regression and compared the prognostic accuracy of PVF variables through receiver operating characteristic (ROC) curve analysis. RESULTS: Among 187 patients (mean age 76.4 ± 10.5 years, 51.3% primary etiology), residual mitral regurgitation (MR) ≤mild was observed in 147 (82.4%) patients and 105 (56.2%) had SD-PVF post-TEER. Patients with SD-PVF had a lower incidence of >2+ residual MR after clip deployment, at 30 days (2.1% vs. 13.1%; p = 0.005) and at 1 year (1.4% vs. 9%; p = 0.08). SD-PVF post-TEER was independently associated with the primary endpoint (HR = 0.59, 95% CI = 0.39-0.87; p = 0.009). ROC curve analysis of the prognostic accuracy of SD-PVF demonstrated an AUC of 0.64 (95% CI = 0.54-0.73), comparable to other quantitative measures of PVF. CONCLUSION: Assessing PVF morphology after clip deployment offers a simple prognostic tool for patients undergoing mitral TEER. Multicenter cohorts will be necessary to further investigate its prognostic value.

Pericardial hydatid cysts presenting with atrial flutter and mitral regurgitation.

Despite being a rare phenomenon, pericardial hydatid cysts present unique diagnostic challenges and require a multimodality imaging as well as a multidisciplinary approach for a curative management. The authors here present a case of a middle aged man who was referred to them for management of new onset atrial flutter with mitral regurgitation.

Hospitalization of Symptomatic Patients With Heart Failure and Moderate to Severe Functional Mitral Regurgitation Treated With MitraClip: Insights From RESHAPE-HF2.

BACKGROUND: For patients with functional mitral regurgitation (FMR) and symptomatic heart failure (HF), randomized trials of mitral transcatheter edge-to-edge repair (M-TEER) have produced conflicting results. OBJECTIVES: This study sought to assess the impact of M-TEER on hospitalization rates, and explore the effects of M-TEER on patients who did or did not have a history of recent HF hospitalizations before undergoing M-TEER. METHODS: RESHAPE-HF2 (Randomized Investigation of the MitraClip Device in Heart Failure: 2nd Trial in Patients with Clinically Significant Functional Mitral Regurgitation) included patients with symptomatic HF and moderate to severe FMR (mean effective regurgitant orifice area 0.25 cm2; 14% >0.40 cm2, 23% <0.20 cm2) and showed that M-TEER reduced recurrent HF hospitalizations with and without the addition of cardiovascular (CV) death and improved quality of life. We now report the results of prespecified analyses on hospitalization rates and for the subgroup of patients (n = 333) with a HF hospitalization in the 12 months before randomization. RESULTS: At 24 months, the time to first event of CV death or HF hospitalization (HR: 0.65; 95% CI: 0.49-0.85; P = 0.002), the rate of recurrent CV hospitalizations (rate ratio [RR]: 0.75; 95% CI: 0.57-0.99; P = 0.046), the composite rate of recurrent CV hospitalizations and all-cause mortality (RR: 0.74; 95% CI: 0.57-0.95; P = 0.017), and of recurrent CV death and CV hospitalizations (RR: 0.76; 95% CI: 0.58-0.99; P = 0.040), were all lower in the M-TEER group. The RR of recurrent hospitalizations for any cause was 0.82 (95% CI: 0.63-1.07; P = 0.15) for patients in the M-TEER group vs control group patients. Patients randomized to M-TEER lost fewer days due to death or HF hospitalization (13.9% [95% CI: 13.0%-14.8%] vs 17.4% [95% CI: 16.4%-18.4%] of follow-up time; P < 0.0001, and 1,067 vs 1,776 total days lost; P < 0.0001). Patients randomized to M-TEER also had better NYHA functional class at 30 days and at 6, 12, and 24 months of follow-up (P < 0.0001). A history of HF hospitalizations before randomization was associated with worse outcomes and greater benefit with M-TEER on the rate of the composite of recurrent HF hospitalizations and CV death (Pinteraction = 0.03) and of recurrent HF hospitalizations within 24 months (Pinteraction = 0.06). CONCLUSIONS: These results indicate that a broader application of M-TEER in addition to optimal guideline-directed medical therapy should be considered among patients with symptomatic HF and moderate to severe FMR, particularly in those with a history of a recent hospitalization for HF.