Impact of Myocardial Scar on Prognostic Implication of Secondary Mitral Regurgitation in Heart Failure

ObjectivesThe objective of the present study was to use cardiovascular magnetic resonance (CMR) to examine the natural history of secondary MR severity and the implication of left ventricular (LV) scar on its prognostic significance.BackgroundThere is a need for further understanding of the prognostic implication of secondary mitral regurgitation (MR) given the heterogeneous findings of the 2 recent randomized trials on percutaneous mitral intervention in patients with secondary MR.MethodsPatients with heart failure were enrolled into a prospective observational registry between 2008 and 2019. Outcomes were a composite of all-cause death, heart transplantation, or LV assist device implantation at follow-up. CMR was used to quantify the mitral regurgitation volume and mitral regurgitation fraction (MRF) along with scar burden utilizing late gadolinium enhancement. Patients were categorized into 4 subgroups based on presence and tertiles of scar extent: no scar, limited scar (scar burden 1% to 4%), intermediate scar (scar burden 5% to 20%), and extensive scar (scar burden >20%).ResultsAmong patients (n = 441) included in the study (age 59 ± 14 years, 43% with ischemic etiology), 85 (19%) experienced an adverse event. MRF ≥30% was associated with increased risk of events among the study group (hazard ratio: 1.74; 95% confidence interval: 1.10 to 2.76; p = 0.02). When stratified by presence or absence of scar, MRF ≥30% was associated with events only among patients with scar (hazard ratio: 1.67; 95% confidence interval: 1.02 to 2.76; p = 0.04) but not among patients without scar. On further classification of patients with scar, the prognostic significance of secondary MR was observed primarily among patients with intermediate scar burden.ConclusionsThe natural history of secondary MR is complex, and outcomes are affected by severity of MR and vary depending upon the extent of scar. (DeBakey Cardiovascular Magnetic Resonance Study [DEBAKEY-CMR]; NCT04281823)     

Combined Tricuspid and Mitral Versus Isolated Mitral Valve Repair for Severe MR and TR: An Analysis From the TriValve and TRAMI Registries

ObjectivesThe aim of this study was to retrospectively compare the characteristics, procedural courses, and outcomes of patients presenting with concomitant mitral regurgitation (MR) and tricuspid regurgitation (TR) in the TriValve (Transcatheter Tricuspid Valve Therapies) and TRAMI (Transcatheter Mitral Valve Interventions) registries.BackgroundTranscatheter mitral edge-to-edge valve repair (TMVR) has been shown to be successful in patients with severe MR. Lately, edge-to-edge repair has also emerged as a possible treatment for severe TR in patients at high risk for cardiac surgery. In patients with both severe MR and TR, the yield of concomitant transcatheter mitral and tricuspid valve repair (TMTVR) for patients at high surgical risk is unknown.MethodsThe characteristics, procedural data, and 1-year outcomes of all patients in the international multicenter TriValve registry and the German multicenter TRAMI registry, who presented with both severe MR and TR, were retrospectively compared. Patients in TRAMI (n = 106) underwent isolated TMVR, while those in TriValve (n = 122) additionally underwent concurrent TMTVR in compassionate and/or off-label use.ResultsAll 228 patients (mean age 77 ± 8 years, 44.3% women) presented with significant dyspnea at baseline (New York Heart Association functional class III or IV in 93.9%), without any differences in the rates of pulmonary hypertension and chronic pulmonary disease. The proportion of patients with left ventricular ejection fraction <30% was higher in the TMVR group (34.9% vs. 18.0%; p < 0.001), while patients in the TMTVR group had lower glomerular filtration rates. At discharge, MR was comparably reduced in both groups. At 1 year, overall all-cause mortality was 34.0% in the TMVR group and 16.4% in the TMTVR group (p = 0.035, Cox regression). On multivariate analysis, TMTVR was associated with a 2-fold lower mortality rate (hazard ratio: 0.52; p = 0.02). The rate of patients in New York Heart Association functional class ≤II at 1 year did not differ (69.4% vs. 67.0%; p = 0.54).ConclusionsConcurrent TMTVR was associated with a higher 1-year survival rate compared with isolated TMVR in patients with both MR and TR. Further randomized trials are needed to confirm these results.     

Long-Term Outcomes of Patients With Elevated Mitral Valve Pressure Gradient After Mitral Valve Edge-to-Edge Repair

ObjectivesThe aim of this study was to investigate the adverse impact of elevated postprocedural mitral valve pressure gradient (MPG) on outcome in a real-world population of patients with severe mitral regurgitation (MR) who underwent transcatheter mitral valve edge-to-edge repair (TEER).BackgroundTEER has become a routine treatment alternative for patients with severe MR at high surgical risk. The consequences of elevated MPG after TEER have been subject to controversial debates.MethodsAll consecutive patients undergoing TEER for either severe degenerative MR (DMR) or functional MR (FMR) at a high-volume center between September 2008 and January 2020 were prospectively included and followed periodically. Postprocedural MPG by discharge transthoracic echocardiography was considered elevated at ≥5 mm Hg. The primary combined endpoint was death or heart failure rehospitalization after 5 years.ResultsA total of 713 patients undergoing TEER (DMR, n = 265; FMR, n = 445) were included. Elevated postprocedural MPG was present in 37.0% of those with DMR (n = 98) and 22.0% of those with FMR (n = 98). In contrast to patients with FMR, 6-minute walk distance did not improve in patients with DMR with elevated MPG. Kaplan-Meier analyses did not demonstrate significant differences for the primary endpoint in patients with DMR (low vs elevated MPG, 67.3% vs 74.4%; P = 0.06) and those with FMR (78.6% vs 74.8%; P = 0.54). After adjustment, elevated MPG was an independent predictor of the primary endpoint in patients with DMR (HR: 1.59; 95% CI: 1.03-2.45; P = 0.034) but not in those with FMR (HR: 0.87; 95% CI: 0.63-1.22; P = 0.43).ConclusionsElevated postprocedural MPG is an independent predictor of adverse clinical and functional outcomes in patients with DMR but not in those with FMR     

Valve Strain Quantitation in Normal Mitral Valves and Mitral Prolapse With Variable Degrees of Regurgitation

ObjectivesThe aim of this study was to quantitate patient-specific mitral valve (MV) strain in normal valves and in patients with mitral valve prolapse with and without significant mitral regurgitation (MR) and assess the determinants of MV strain.BackgroundFew data exist on MV deformation during systole in humans. Three-dimensional echocardiography allows for dynamic MV imaging, enabling digital modeling of MV function in health and disease.MethodsThree-dimensional transesophageal echocardiography was performed in 82 patients, 32 with normal MV and 50 with mitral valve prolapse (MVP): 12 with mild mitral regurgitation or less (MVP ? MR) and 38 with moderate MR or greater (MVP + MR). Three-dimensional MV models were generated, and the peak systolic strain of MV leaflets was computed on proprietary software.ResultsLeft ventricular ejection fraction was normal in all groups. MV annular dimensions were largest in MVP + MR (annular area: 13.8 ± 0.7 cm²) and comparable in MVP ? MR (10.6 ± 1 cm²) and normal valves (10.5 ± 0.3 cm²; analysis of variance: p < 0.001). Similarly, MV leaflet areas were largest in MVP + MR, particularly the posterior leaflet (8.7 ± 0.5 cm²); intermediate in MVP ? MR (6.5 ± 0.7 cm²); and smallest in normal valves (5.5 ± 0.2 cm²; p < 0.0001). Strain was overall highest in MVP + MR and lowest in normal valves. Patients with MVP ? MR had intermediate strain values that were higher than normal valves in the posterior leaflet (p = 0.001). On multivariable analysis, after adjustment for clinical and MV geometric parameters, leaflet thickness was the only parameter that was retained as being significantly correlated with mean MV strain (r = 0.34; p = 0.008).ConclusionsMVs that exhibit prolapse have higher strain compared to normal valves, particularly in the posterior leaflet. Although higher strain is observed with worsening MR and larger valves and annuli, mitral valve leaflet thickness—and, thus, underlying MV pathology—is the most significant independent determinant of valve deformation. Future studies are needed to assess the impact of MV strain determination on clinical outcome.     

Risk of Surgical Mitral Valve Repair for Primary Mitral Regurgitation

BackgroundRisk estimation for surgical intervention is an essential component of heart team shared decision-making. However, current mitral valve (MV) surgery risk models used in practice lack etiologic or procedural specificity.ObjectivesThe purpose of this study was to establish a comprehensive method for assessment of operative risk of MV repair of primary mitral regurgitation (MR).MethodsA novel etiology and procedure-specific algorithm identified 53,462 consecutive (July 2014 to June 2020) intention-to-treat MV repair patients with primary MR from The Society of Thoracic Surgeons Adult Cardiac Surgery Database. Risk models were fit for 30-day operative mortality, mortality and/or major morbidity, and conversion-to-replacement (CONV). As-treated mortality and morbidity models were derived separately.ResultsEvent rates for mortality (n = 619; 1.16%), mortality plus morbidity (n = 4,746; 8.88%), and CONV (n = 3,399; 6.36%) were low. Mortality was higher in CONV patients vs repair (3.18% vs 1.02%). All event rates were lower with increasing program volumes. The mortality risk model had excellent discrimination (AUC: 0.807) and calibration and confirmed very low mortality risk for isolated MV repair for primary MR, with mean mortality risk of 1.16% and median of 0.55% (IQR: 0.30%-1.17%) with 90th and 95th percentiles 2.48% and 3.99%, respectively. The mortality risk was <0.5% in patients <65 years of age, with 97% of the total population across age groups having a risk of <3%. Only 1 in 4 patients age 75 or older had >3% estimated risk of mortality.ConclusionsThis etiologic and procedure-specific risk model establishes that the contemporary mortality risk of MV repair for primary MR is <1% for the vast majority of patients.     

Online Quantitative Aortographic Assessment of Aortic Regurgitation After TAVR: Results of the OVAL Study

ObjectivesThe aim of this study was to investigate the online assessment feasibility of aortography using videodensitometry in the catheterization laboratory during transcatheter aortic valve replacement (TAVR).BackgroundQuantitative assessment of regurgitation after TAVR through aortography using videodensitometry is simple, reproducible, and validated in vitro, in vivo, in clinical trials, and in “real-world” patients. However, thus far the assessment has been done offline.MethodsThis was a single center, prospective, proof-of-principle, feasibility study. One hundred consecutive patients with aortic stenosis and indications to undergo TAVR were enrolled. All final aortograms were analyzed immediately after acquisition in the catheterization laboratory and were also sent to an independent core laboratory for blinded offline assessment. The primary endpoint of the study was the feasibility of the online assessment of regurgitation (percentage of analyzable cases). The secondary endpoint was the reproducibility of results between the online assessment and the offline analysis by the core laboratory.ResultsPatients’ mean age was 81 ± 7 years, and 56% were men. The implanted valves were either SAPIEN 3 (97%) or SAPIEN 3 Ultra (3%). The primary endpoint of online feasibility of analysis was 92% (95% confidence interval [CI]: 86% to 97%) which was the same feasibility encountered by the core laboratory (92%; 95% CI: 86% to 97%). Reproducibility assessment showed a high correlation between online and core laboratory evaluations (R² = 0.87, p < 0.001), with an intraclass correlation coefficient of 0.962 (95% CI: 0.942 to 0.975; p < 0.001).ConclusionsThis study showed high feasibility of online quantitative assessment of regurgitation and high agreement between the online examiner and core laboratory. These results may pave the way for the application of videodensitometry in the catheterization laboratory after TAVR. (Online Videodensitometric Assessment of Aortic Regurgitation in the Cath-Lab [OVAL]; NCT04047082)     

Differences in Cardiac Remodeling in Left-Sided Valvular Regurgitation: Implications for Optimal Definition of Significant Aortic Regurgitation

BackgroundGrading of aortic regurgitation (AR) and mitral regurgitation (MR) is similar in the cardiology guidelines despite distinct differences in left ventricular (LV) adaptive pathophysiology.ObjectivesThis study compared differences in LV remodeling in patients with similar degrees of AR and MR severity and evaluated optimal cutoffs for significant AR in relation to the outcome of aortic valve replacement or repair (AVR) during follow-up.MethodsFrom 2008 to 2018, consecutive patients with isolated AR or MR who had cardiac magnetic resonance (CMR) were identified and CMR parameters were compared. Patients with left ventricular ejection fraction (LVEF) <50%, ischemic scar >5%, valve stenosis, or concomitant regurgitation were excluded. Patients were followed longitudinally for AVR.ResultsBaseline characteristics of isolated AR (n = 418) and isolated MR (n = 1,073) were comparable except for higher male proportion and hypertension in AR, while heart failure was more prevalent in MR. Indexed LV end-diastolic and end-systolic volumes and mass were higher in AR compared with MR at the same level of regurgitant fraction. During follow-up (mean 2.1 years), 18.7% of AR patients underwent AVR based on symptoms or LV remodeling. Interestingly, 38.0% of patients that underwent AVR within 3 months after CMR did not meet severe AVR by current guidelines of AR severity. AR regurgitant fraction>35% had high sensitivity (86%) and specificity (88%) for identifying patients who underwent AVR.ConclusionsFor similar regurgitation severity, LV remodeling is different in AR compared with MR. Cardiac symptoms and significant LV remodeling in AR requiring AVR occur frequently in patients with less severity than currently proposed. The study findings suggest that the optimal threshold for severe AR with CMR is different than MR and is lower than currently stated in the guidelines.     

Attenuated Mitral Leaflet Enlargement Contributes to Functional Mitral Regurgitation After Myocardial Infarction

BackgroundMitral leaflet enlargement has been identified as an adaptive mechanism to prevent mitral regurgitation in dilated left ventricles (LVs) caused by chronic aortic regurgitation (AR). This enlargement is deficient in patients with functional mitral regurgitation, which remains frequent in the population with ischemic cardiomyopathy. Maladaptive fibrotic changes have been identified in post-myocardial infarction (MI) mitral valves. It is unknown if these changes can interfere with valve growth and whether they are present in other valves.ObjectivesThis study sought to test the hypothesis that MI impairs leaflet growth, seen in AR, and induces fibrotic changes in mitral and tricuspid valves.MethodsSheep models of AR, AR + MI, and controls were followed for 90 days. Cardiac magnetic resonance, echocardiography, and computed tomography were performed at baseline and 90 days to assess LV volume, LV function, mitral regurgitation and mitral leaflet size. Histopathology and molecular analyses were performed in excised valves.ResultsBoth experimental groups developed similar LV dilatation and dysfunction. At 90 days, mitral valve leaflet size was smaller in the AR + MI group (12.8 ± 1.3 cm² vs. 15.1 ± 1.6 cm², p = 0.03). Mitral regurgitant fraction was 4% ± 7% in the AR group versus 19% ± 10% in the AR + MI group (p = 0.02). AR + MI leaflets were thicker compared with AR and control valves. Increased expression of extracellular matrix remodeling genes was found in both the mitral and tricuspid leaflets in the AR + MI group.ConclusionsIn these animal models of AR, the presence of MI was associated with impaired adaptive valve growth and more functional mitral regurgitation, despite similar LV size and function. More pronounced extracellular remodeling was observed in mitral and tricuspid leaflets, suggesting systemic valvular remodeling after MI.     

Effect of Transcatheter Aortic Valve Replacement on Concomitant Mitral Regurgitation and Its Impact on Mortality

ObjectivesThe purpose of this study was to examine the impact of residual mitral regurgitation (MR) on mortality in patients undergoing transcatheter aortic valve replacement (TAVR).BackgroundMR is common in patients undergoing TAVR. Data on optimal management of patients with significant MR after TAVR are limited.MethodsThe registry consisted of 16 TAVR centers (n = 7,303). Outcomes of patients with ≥ moderate versus lesser grade MR after TAVR were compared.ResultsIn 1,983 (27.2%) patients, baseline MR grade was ≥ moderate. MR regressed in 874 (44.1%) patients and persisted in 1,109 (55.9%) after TAVR. Four-year mortality was higher for those with MR persistence, but not for those with MR regression after TAVR, compared with nonsignificant baseline MR (43.8% vs. 35.1% vs. 32.4%; hazard ratio [HR]: 1.38; p = 0.008; HR: 1.02; p = 0.383, respectively). New York Heart Association functional class III to IV after TAVR was more common in those with MR persistence vs. regression (14.4% vs. 3.9%; p < 0.001). In a propensity score–matched cohort (91 patients’ pairs), with significant residual MR after TAVR who did or did not undergo staged mitral intervention, staged intervention was associated with a better functional class through 1 year of follow-up (82.4% vs. 33.3% New York Heart Association functional class I or II; p < 0.001), and a numerically lower 4-year mortality, which was not statistically significant (64.6% vs. 37.5%; HR: 1.66; p = 0.097).ConclusionsRisk stratification based on improvement in MR and symptoms after TAVR can identify patients at increased mortality risk after TAVR. These patients may benefit from a staged transcatheter mitral intervention, but this requires further proof from future studies. (Transcatheter Treatment for Combined Aortic and Mitral Valve Disease. The Aortic+Mitral TRAnsCatheter [AMTRAC] Valve Registry [AMTRAC]; NCT04031274).     

Transcatheter Mitral Valve Repair in Cardiogenic Shock and Mitral Regurgitation: A Patient-Level,Multicenter Analysis

ObjectivesThe aim of this study was to evaluate the outcome of transcatheter mitral valve repair (TMVr) in patients with cardiogenic shock and significant mitral regurgitation (MR).BackgroundPatients in cardiogenic shock with severe MR have a poor prognosis in the setting of conventional medical therapy. Because of its favorable safety profile, TMVr is being increasingly used as an acute therapy in this population, though its efficacy remains unknown.MethodsA multicenter, collaborative, patient-level analysis was conducted. Patients with cardiogenic shock and moderate to severe (3+) or severe (4+) MR who were not surgical candidates were treated with TMVr. The primary outcome was in-hospital mortality. Secondary outcomes included 90-day mortality, heart failure (HF) hospitalization, and the combined event rate of 90-day mortality and HF hospitalization following dichotomization by TMVr device success.ResultsBetween January 2011 and February 2019, 141 patients across 14 institutions met the inclusion criteria. In-hospital mortality occurred in 22 patients (15.6%), at 90 days in 38 patients (29.5%), and at one year in 55 patients (42.6%). Median length of hospital stay following TMVr was 10 days (interquartile range: 6 to 20 days). HF hospitalization occurred in 26 patients (18.4%) at a median of 73 days (interquartile range: 26 to 546 days). When stratified by TMVr procedural results, successful TMVr reduced rates of in-hospital mortality (hazard ratio [HR]: 0.36; 95% confidence interval [CI]: 0.13 to 0.98; p = 0.04), 90-day mortality (HR: 0.36; 95% CI: 0.16 to 0.78; p = 0.01), and the composite of 90-day mortality and HF hospitalization (HR: 0.41; 95% CI: 0.19 to 0.90; p = 0.03).ConclusionsTMVr may improve short- and intermediate-term mortality in high-risk patients with cardiogenic shock and moderate to severe MR. Randomized studies are needed to definitively establish MR as a therapeutic target in patients with cardiogenic shock.     

American Society of Echocardiography Algorithm for Degenerative Mitral Regurgitation: Comparison With CMR

ObjectivesThe purpose of this study was to compare the American Society of Echocardiography (ASE) algorithm for assessing mitral regurgitation (MR) to cardiac magnetic resonance (CMR) and left ventricular (LV) remodeling following mitral intervention.BackgroundThe ASE recommends integrating multiple echocardiographic parameters for assessing MR. The ASE guidelines include an algorithm that weighs the parameters and highlights those considered indicative of definitely mild or definitely severe MR.MethodsWe prospectively enrolled 152 (age 62 ± 13 years; 59% male) patients with degenerative MR who underwent ASE algorithm-guided echocardiographic and CMR grading of MR severity. Using the ASE algorithm, patients were graded as definitely mild, grade I, grade II, grade III, grade IV, or definitely severe MR. CMR MR volume was graded as mild (<30 mL), grade II moderate (30-44 mL), grade III moderate (45-59 mL), or severe (≥60 mL). A subgroup of 63 patients underwent successful mitral intervention, of whom 48 had postintervention CMR.ResultsOnly 52% of patients with definitely severe MR by the ASE algorithm had severe MR by CMR, and 10% had mild MR by CMR. There was an increase in post mitral intervention LV reverse remodeling with worsening MR severity using CMR (P < 0.0001) but not the ASE algorithm (P = 0.07). Severe MR by CMR was an independent predictor of post mitral intervention LV reverse remodeling and definitely severe MR by the ASE algorithm was not.ConclusionsIn patients with degenerative MR, agreement between CMR and the ASE algorithm was suboptimal. Severe MR by CMR was an independent predictor of post mitral intervention LV reverse remodeling, whereas definitely severe MR by the ASE algorithm was not. These findings suggest an important role for CMR in surgical decision making in degenerative MR. (Comparison Study of Echocardiography and Cardiovascular Magnetic Resonance Imaging in the Assessment of Mitral and Aortic Regurgitation; NCT04038879)     

Clinical Outcomes With Transcatheter Edge-to-Edge Repair in Atrial Functional MR From the EXPAND Study

BackgroundAlthough transcatheter edge-to-edge repair (TEER) has been shown to improve clinical outcomes and improve quality of life in patients with symptomatic secondary mitral regurgitation (SMR) and left ventricular dysfunction, its effect in patients with atrial SMR (aSMR) has not been well described.ObjectivesThe aim of this study was to assess the safety, echocardiographic outcomes, and clinical effectiveness of TEER for aSMR.MethodsPatients with aSMR in the prospective, observational, multicenter EXPAND (A Contemporary, Prospective, Multi-Center Study Evaluating Real-World Experience of Performance and Safety for the Next Generation of MitraClip Devices) study were identified by an echocardiography core laboratory. Follow-up occurred at discharge, 30 days, and 1 year. Key endpoints included mitral regurgitation (MR) severity, functional class, heart failure hospitalizations, mortality, and 30-day major adverse events.ResultsAmong 1,041 patients enrolled in EXPAND, 835 patients had evaluable echocardiograms at baseline. Of these, 53 patients had aSMR and 360 had ventricular SMR (vSMR). In the aSMR cohort, TEER resulted in a significant reduction in MR through 1 year (MR grade ≤2 in 100.0%), significantly increased 1-year Kansas City Cardiomyopathy Questionnaire score (+26.6 ± 30.5 points; P < 0.0001), and improved functional class from baseline, similar to the effects among patients with vSMR (MR grade ≤2 in 99.5% at 1 year, 1-year increase in Kansas City Cardiomyopathy Questionnaire score 21.23 ± 24.92 points). Major adverse events at 30 days and leaflet adverse events at 1 year were infrequent in both groups.ConclusionsIn a prospective, real-world, global registry, TEER for aSMR was associated with significant MR reduction and improvement in quality of life and functional class, similar to patients with vSMR. This suggests that TEER may provide clinical benefit in patients with atrial fibrillation with SMR in the setting of heart failure with preserved ejection fraction. (The MitraClip® EXPAND Study of the Next Generation of MitraClip® Devices; NCT03502811)     

Management and Outcome of Failed Percutaneous Edge-to-Edge Mitral Valve Plasty: Insight From an International Registry

ObjectivesThis study evaluated the incidence, management, and outcome of patients who experienced MitraClip (Abbott Vascular) failure secondary to loss of leaflet insertion (LLI), single leaflet detachment (SLD), or embolization.BackgroundTranscatheter edge-to-edge repair with MitraClip is an established therapy for the treatment of mitral regurgitation (MR), but no data exist regarding the prevalence and outcome according to the mode of clip failure.MethodsBetween January 2009 and December 2020, we retrospectively screened 4,294 procedures of MitraClip performed in 19 centers. LLI was defined as damage to the leaflet where the MitraClip was attached, SLD as demonstration of complete separation between the device and a single leaflet tissue, and clip embolization as loss of contact between MitraClip and both leaflets.ResultsA total of 147 cases of MitraClip failure were detected (overall incidence = 3.5%), and these were secondary to LLI or SLD in 47 (31.9%) and 99 (67.3%) cases, respectively, whereas in 1 (0.8%) case clip embolization was observed. MitraClip failure occurred in 67 (45.5%) patients with functional MR, in 64 (43.5%) patients with degenerative MR, and 16 (10.8%) with mixed etiology. Although the majority of MitraClip failures were detected before discharge (47 intraprocedural and 42 in the hospital), up to 39.5% of cases were diagnosed at follow-up. In total, 80 (54.4%) subjects underwent a redo procedure, either percutaneously with MitraClip (n = 51, 34.7%) or surgically (n = 36, 24.5%) including 4 cases of surgical conversion of the index procedure and 7 cases of bailout surgery after unsuccessful redo MitraClip. After a median follow-up of 163 days (IQR: 22-720 days), 50 (43.9%) subjects presented moderate to severe MR, and 43 (29.3%) patients died. An up-front redo MitraClip strategy was associated with a trend toward a reduced rate of death at follow-up vs surgical or conservative management (P = 0.067), whereas postprocedural acute kidney injury, age, and moderate to severe tricuspid regurgitation were independent predictors of death.ConclusionsMitraClip failure secondary to LLI and SLD is not a rare phenomenon and may occur during and also beyond hospitalization. Redo MitraClip strategy demonstrates a trend toward a reduced risk of death compared with bailout surgery and conservative management. A third of those patients remained with more than moderate MR and had substantial mortality at the intermediate-term follow-up.     

Sex-Related Clinical Characteristics and Outcomes of Patients Undergoing Transcatheter Edge-to-Edge Repair for Secondary Mitral Regurgitation

ObjectivesThe authors sought to assess sex-based differences in characteristics and outcomes of patients undergoing transcatheter edge-to-edge mitral valve repair (TMVR) for secondary mitral regurgitation (SMR).BackgroundSubgroup analysis from the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial indicated potential sex-related differences in outcomes after TMVR. The impact of sex on results after TMVR in a real-world setting is unknown.MethodsThe authors assessed clinical outcomes and echocardiographic parameters in women and men undergoing TMVR for SMR between 2008 and 2018 who were included in the large, international, multicenter real-world EuroSMR registry (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation).ResultsA total of 1,233 patients, including 445 women (36%) and 788 men (64%), were analyzed. Although women were significantly older and had fewer comorbidities than men, TMVR was equally effective in women and men (mitral regurgitation [MR] grade ≤2+ at discharge: 93.2% vs. 94.6% for women vs. men; p = 0.35). All-cause mortality at 1 year (17.9% vs. 18.9%, adjusted hazard ratio: 0.806; p = 0.46) and at 2-year follow-up (26.5% vs. 26.4%, adjusted hazard ratio: 0.757; p = 0.26) were similar in women versus men after multivariate regression analysis. Durability of MR reduction, improvement in symptoms, quality of life, and functional capacity did also not differ during follow-up.ConclusionsResults from the EuroSMR registry confirmed effective and similar MR reduction with TMVR in women and men. There were no sex-related differences in clinical outcomes up to 2 years of follow-up.     

Regurgitant Volume/Left Ventricular End-Diastolic Volume Ratio: Prognostic Value in Patients With Secondary Mitral Regurgitation

ObjectivesThe purpose of this study was to investigate the prognostic implications of the ratio of mitral regurgitant volume (RVol) to left ventricular (LV) end-diastolic volume (EDV) in patients with significant secondary mitral regurgitation (MR).BackgroundQuantification of secondary MR remains challenging, and its severity can be over- or underestimated when using the proximal isovelocity surface area method, which does not take LV volume into account. This limitation can be addressed by normalizing mitral RVol to LVEDV.MethodsA total of 379 patients (mean age 67 ± 11 years; 63% male) with significant (moderate and severe) secondary MR were divided into 2 groups according to the RVol/EDV ratio: RVol/EDV ≥20% (greater MR/smaller EDV) and <20% (smaller MR/larger EDV). The primary endpoint was all-cause mortality.ResultsDuring median (interquartile range) follow-up of 50 (26 to 94) months, 199 (52.5%) patients died. When considering patients receiving medical therapy only, patients with RVol/EDV ratio ≥20% tended to have higher mortality rates than those with RVol/EDV ratio <20% (5-year estimated rates 24.1% vs. 18.4%, respectively; p = 0.077). Conversely, when considering the entire follow-up period including mitral valve interventions, patients with a higher RVol/EDV ratio (≥20%) had lower rates of all-cause mortality compared with patients with RVol/EDV ratio <20% (5-year estimated rates 39.0% vs. 44.8%, respectively; p = 0.018). On multivariable analysis, higher RVol/EDV ratio (per 5% increment as a continuous variable) was independently associated with lower all-cause mortality (0.93; p = 0.023).ConclusionsIn patients with significant secondary MR treated medically, survival tended to be lower in those with a higher RVol/EDV ratio. Conversely, a higher RVol/EDV ratio was independently associated with reduced all-cause mortality. when mitral valve interventions were taken into consideration     

Transcatheter Treatment of Residual Significant Mitral Regurgitation Following TAVR: A Multicenter Registry

ObjectivesThe aim of this study was to describe baseline characteristics, and periprocedural and mid-term outcomes of patients undergoing transcatheter mitral valve interventions post-transcatheter aortic valve replacement (TAVR) and examine their clinical benefit.BackgroundThe optimal management of residual mitral regurgitation (MR) post-TAVR is challenging.MethodsThis was an international registry of 23 TAVR centers.ResultsIn total, 106 of 24,178 patients (0.43%) underwent mitral interventions post-TAVR (100 staged, 6 concomitant), most commonly percutaneous edge-to-edge mitral valve repair (PMVR). The median interval post-TAVR was 164 days. Mean age was 79.5 ± 7.2 years, MR was >moderate in 97.2%, technical success was 99.1%, and 30-day device success rate was 88.7%. There were 18 periprocedural complications (16.9%) including 4 deaths. During a median follow-up of 464 days, the cumulative risk for 3-year mortality was 29.0%. MR grade and New York Heart Association (NYHA) functional class improved dramatically; at 1 year, MR was moderate or less in 90.9% of patients (mild or less in 69.1%), and 85.9% of patients were in NYHA functional class I/II. Staged PMVR was associated with lower mortality versus medical treatment (57.5% vs. 30.8%) in a propensity-matched cohort (n = 156), but this was not statistically significant (hazard ratio: 1.75; p = 0.05).ConclusionsFor patients who continue to have significant MR, remain symptomatic post-TAVR, and are anatomically suitable for transcatheter interventions, these interventions are feasible, safe, and associated with significant improvement in MR grade and NYHA functional class. These results apply mainly to PMVR. A staged PMVR strategy was associated with markedly lower mortality, but this was not statistically significant. (Transcatheter Treatment for Combined Aortic and Mitral Valve Disease. The Aortic+Mitral TRAnsCatheter Valve Registry [AMTRAC]; NCT04031274)     

Prognostic Impact of Extra–Mitral Valve Cardiac Involvement in Patients With Primary Mitral Regurgitation

BackgroundIn patients with severe primary mitral regurgitation (MR), the indication for surgery is currently based on the presence of symptoms, left ventricular dilatation and dysfunction, atrial fibrillation, and pulmonary hypertension.ObjectivesThe aim of this study was to evaluate the prognostic impact of the presence of extra–mitral valve cardiac involvement (including known risk factors but also severe left atrial [LA] dilatation and right ventricular [RV] dysfunction) in a large multicenter study of patients with primary MR.MethodsPatients with severe primary MR undergoing surgery were included and categorized according to the extent (highest) of cardiac involvement: group 0, no cardiac involvement; group 1, left ventricular involvement; group 2, LA involvement; group 3, pulmonary vasculature or tricuspid valve involvement; or group 4, RV involvement. The outcome was all-cause mortality.ResultsA total of 1,106 patients were included (mean age 63 ± 12 years, 68% male). In total, 377 patients (34%) were classified in group 0, 239 (22%) in group 1, 213 (19%) in group 2, 180 (16%) in group 3, and 97 (9%) in group 4. Kaplan-Meier curve analysis revealed significantly worse survival (log-rank chi-square = 43.4; P < 0.001) with higher group. On multivariable analysis, age, male sex, chronic obstructive pulmonary disease, kidney function, and group of cardiac involvement were independently associated with all-cause mortality. For each increase in group, a 17% higher risk for all-cause mortality was observed (95% CI: 1.051-1.313; P = 0.005) during a median follow-up time of 88 months.ConclusionsIn patients with severe primary MR, a novel classification system based on extra–mitral valve cardiac involvement may help refine risk stratification and timing of surgery, particularly including severe LA dilatation and RV dysfunction in the assessment.     

Transcatheter Mitral Cerclage Ventriculoplasty: From Bench to Bedside

BackgroundTranscatheter mitral valve repair is beneficial in patients with mitral regurgitation (MR), left ventricular dysfunction, and persistent symptoms despite maximally tolerated medical therapy.ObjectivesThe aim of this study was to evaluate the safety and feasibility of transcatheter mitral cerclage ventriculoplasty in patients with MR and either heart failure with reduced ejection fraction or preserved ejection fraction and in subjects with prior edge-to-edge repair but persistent or recurrent symptomatic MR.MethodsThe National Heart, Lung, and Blood Institute Division of Intramural Research Transcatheter Mitral Cerclage Ventriculoplasty Early Feasibility Study (NCT03929913) was an investigator-initiated prospective multicenter study. The primary endpoint was technical success measured at exit from the catheterization laboratory. Follow-up included heart failure quality-of-life assessments and serial imaging with echocardiography and cardiac computed tomography.ResultsNineteen subjects consented and underwent cerclage, 63% with heart failure with reduced ejection fraction and 37% with heart failure with preserved ejection fraction, with ischemic cardiomyopathy in 26% and nonischemic cardiomyopathy in 74%. There were no procedural deaths, strokes, or transient ischemic attacks or other major cardiovascular adverse events. The primary endpoint was met in 17 subjects. Cerclage induced sustained reductions in mitral regurgitant volume (?41%) and effective orifice area (?33%) after a median of 337 days. Cerclage resulted in improvements in 6-minute walking distance (+78 m) and Kansas City Cardiomyopathy Questionnaire Overall Summary Score (+22 points) at 30 days that were maintained after a median of 265 days. New complete heart block developed in 6 of 17 subjects. Three deaths occurred on postprocedural days 79, 159, and 756, unrelated to cerclage.ConclusionsTranscatheter mitral cerclage ventriculoplasty resulted in significant and sustained improvements in mitral regurgitation and in heart failure quality-of-life assessments.     

Insufficient Mitral Leaflet Remodeling in Relation to Annular Dilation and Risk of Residual Mitral Regurgitation After MitraClip Implantation

ObjectivesThe purpose of this study was to determine whether the mitral valve (MV) total leaflet area (TLA)-to-mitral annular area (MAA) (TLA/MAA) ratio measured using 3-dimensional (3D) transesophageal echocardiography (TEE) was associated with residual mitral regurgitation (MR) after MitraClip implantation in patients with secondary MR.BackgroundThe factors influencing the results of MitraClip implantation for secondary MR are controversial. This study hypothesized that insufficient remodeling of the mitral leaflets relative to the annular dilation may be associated with significant MR after MitraClip implantation.MethodsThis study included patients with secondary MR treated with MitraClips. Using 3D TEE dataset, the TLA in diastole and MAA in systole were measured with dedicated software.ResultsIn a total cohort of 119 patients (mean age 74 ± 9 years; 61% male), significant residual MR (≥2+) was present in 43 patients (36%). In patients with significant residual MR, MAA was greater than in patients without residual MR (10.7 ± 2.4 cm² vs. 9.0 ± 2.1 cm²; p < 0.001) whereas no significant difference was observed in TLA (12.2 ± 2.6 cm² vs. 12.0 ± 2.9 cm²; p = 0.836). TLA/MAA ratio was lower in patients with significant residual MR as compared to their counterparts (1.14 ± 0.15 vs. 1.34 ± 0.16; p < 0.001), suggesting insufficient leaflet remodeling relative to annular dilation. On receiver-operating characteristic curve analysis, the TLA/MAA ratio had better discriminative power to identify patients who will have significant residual MR compared to MAA alone (area under the curve [AUC]: 0.830 vs. 0.723; p = 0.049).ConclusionsIn patients with secondary MR, insufficient mitral leaflet remodeling relative to the annulus dilation, as reflected by a lower TLA/MAA ratio, is associated with significant residual MR after MitraClip implantation.     

Risk Associated With Valvular Regurgitation During Pregnancy

BackgroundPregnancies in women with regurgitant valve lesions are generally considered low risk, but this has not been well studied.ObjectivesThis study determined the frequency of adverse cardiac events (CEs) in pregnant women with moderate or severe regurgitant valve lesions.MethodsMaternal and fetal outcomes in women with moderate or severe chronic valve regurgitation enrolled in a prospective multicenter study on pregnancy outcomes were examined. Adverse CEs included heart failure, sustained arrhythmias, cardiac arrest, or death. A multivariate logistic regression model was used to identify determinants of CEs in women at the highest risk.ResultsOutcomes of 430 pregnancies in women with moderate or severe regurgitant lesions were examined: 145 with mitral regurgitation (MR), 101 with pulmonary regurgitation (PR), 71 with multivalve disease, 73 with tricuspid regurgitation (TR), and 40 with aortic regurgitation (AR). Most women had associated congenital or acquired heart disease. Adverse CEs occurred in 13% of pregnancies: 27% of pregnancies with multivalve disease; 15% with MR; 15% with TR; 5% with AR; and 3% with PR. Maternal mortality was rare. In women with MR, TR, or multivalve disease (n = 289), left ventricular systolic dysfunction (p = 0.001), pulmonary hypertension (p = 0.005), and cardiac events before pregnancy (p < 0.001) were important determinants of CEs during pregnancy.ConclusionsWomen with AR and PR are at low risk for cardiac complications during pregnancy. While many women with MR, TR, and multivalve regurgitation do well during pregnancy, additional clinical variables help stratify those at highest risk. This new information will enhance the quality and precision of preconception counseling and pregnancy planning.