Significant Secondary Mitral Regurgitation Research Articles

Outcomes of mitral TEER in non-responders to cardiac resynchronization therapy: A systematic review and meta-analysis

BackgroundSecondary mitral regurgitation (MR) worsens in 10–15 % of heart failure (HF) patients receiving cardiac resynchronization therapy (CRT). Transcatheter edge-to-edge repair (TEER) with Mitra-Clip (Abbot Vascular, Santa Clara, CA, USA) therapy is associated with improved survival and decreased rates of hospitalization for HF in selected patients with secondary MR. Data on TEER outcomes in CRT-non-responders are limited. The purpose of this meta-analysis was to evaluate outcomes of mitral TEER with Mitra-Clip in CRT-non-responders. MethodsCochrane, Scopus, MEDLINE, and EMBASE were searched for studies discussing outcomes of Mitra-Clip in CRT non-responders. Two reviewers were independently involved in screening studies and extracting relevant data. Individual study incidence rate estimates underwent logit transformation to calculate the weighted summary proportion under the random effect model. ResultsA total of eight reports met the inclusion criteria (439 patients). Mitra-Clip improved MR grade to ≤2+ in 83.8 % and 86.8 % of CRT non-responders at six months and one year, respectively. Symptomatic improvement (New York Heart Association class ≤II) was also found in 71 % and 78.1 % of CRT non-responders at six months and one year, respectively. The pooled overall incidence estimates of mortality at 30 days, 6 months, 1 year, and 2 years were 3.6 %, 9.2 %, 17.8 %, and 25.9 %, respectively. ConclusionTEER with Mitra-Clip in patients with significant secondary MR who do not respond to CRT was associated with MR improvement, alleviation of symptoms, and mortality rates similar to those in the COAPT trial.

Persistence of significant secondary mitral regurgitation post-cardiac resynchronization therapy and survival: a systematic review and meta-analysis : Mitral regurgitation and mortality post-CRT.

Cardiac resynchronization therapy (CRT) significantly reduces secondary mitral regurgitation (MR) in patients with severe left ventricular systolic dysfunction. However, uncertainty remains as to whether improvement in secondary MR correlates with improvement with mortality seen in CRT. We conducted a meta-analysis to determine the association of persistent unimproved significant secondary MR (defined as moderate or moderate-to-severe or severe MR) compared to improved MR (no MR or mild MR) post-CRT with all-cause mortality, cardiovascular mortality, and heart failure hospitalization. A systematic search of PubMed, EMBASE, and Cochrane Library databases till July 31, 2022 identified studies reporting clinical outcomes by post-CRT secondary MR status. In 12 prospective studies of 4954 patients (weighted mean age 66.8years, men 77.8%), the median duration of follow-up post-CRT at which patients were re-evaluated for significant secondary MR was 6months and showed significant relative risk reduction of 30% compared to pre-CRT. The median duration of follow-up post-CRT for ascertainment of main clinical outcomes was 38months. The random effects pooled hazard ratio (95% confidence interval) of all-cause mortality in patients with unimproved secondary MR compared to improved secondary MR was 2.00 (1.57-2.55); p < 0.001). There was insufficient data to evaluate secondary outcomes in a meta-analysis, but limited data that examined the relationship showed significant association of unimproved secondary MR with increased cardiovascular mortality and heart failure hospitalization. The findings of this meta-analysis suggest that lack of improvement in secondary MR post-CRT is associated with significantly elevated risk of all-cause mortality and possibly cardiovascular mortality and heart failure hospitalization. Future studies may investigate approaches to address persistent secondary MR post-CRT to help improved outcome in this population.

Relationship between stress hyperglycemia and worsening heart failure in patients with significant secondary mitral regurgitation

Background and aimsSecondary mitral regurgitation (sMR), a major valvular disease, is prevalent in patients with coronary artery disease (CAD), and is associated with higher incidence of heart failure (HF) and mortality when present in combination with abnormal glucose metabolism. We aimed to evaluate the relationship between stress hyperglycemia ratio (SHR) and worsening HF in CAD patients with significant (grade ≥2) sMR. MethodsWe performed a multi-center observational study of 874 participants with significant sMR following percutaneous coronary intervention (PCI) in the Cardiorenal Improvement-II (CIN-II) cohort. Patients with glucose and glycated hemoglobin (HbA1c) data at admission were included in the analysis, and categorized according to the SHR, the ratio of mmol/L blood glucose to % HbA1c, as quartiles: Q1: <0.74; Q2: 0.74–0.91; Q3: 0.91–1.14; and Q4: ≥1.14. The primary clinical endpoint was worsening HF and the secondary endpoint was major adverse cardiac events (MACE). ResultsOf the 874 participants (64.1 ± 10.8 years, 80% male), 174 showed worsening HF and 226 developed MACE during a median follow-up of 3.7 years (interquartile range: 1.8–6.2 years). Compared to participants in the lowest quartile (Q1) of SHR, the highest quartile group (Q4) was at significantly higher risks of worsening HF (adjusted hazard ratio, 2.44; 95% confidence interval, 1.51–3.94; p< 0.001), while this was not associated with increased risk of MACE (p>0.05) after adjustment for potential covariates. For worsening HF, the results obtained for the normal glucose regulation subgroup may be more meaningful than those for the diabetes mellitus (DM) and pre-DM groups (p-interaction<0.001). For MACE, the acute myocardial infarction (AMI) (Q4 vs. Q1; HR: 0.65, 95%CI: 0.26–1.59) and non-AMI (Q4 vs. Q1; HR: 2.20, 95%CI: 1.36–3.54) subgroups differed significantly on MACE (p-interaction = 0.006). ConclusionsIncreasing SHR is associated with a higher risk of worsening of HF in patients with significant sMR, especially in those with normoglycemia.

Advanced heart failure: a contemporary approach.

Advanced heart failure (HF) is defined as the persistence of severe symptoms despite the use of optimized medical, surgical, and device therapies. These patients require timely advanced treatments, such as heart transplantation or long-term mechanical circulatory support (MCS). Inotropic agents are often used to reduce congestion and increase cardiac output, while renal replacement therapy may be beneficial if necessary. Cardiac resynchronization therapy has clear benefits in patients with HF with reduced ejection fraction, particularly with left bundle branch block (QRS duration > 130 ms). The role of implantable cardioverter-defibrillators in advanced HF patients requires further investigation considering the introduction of novel HF medications. In selected patients with significant secondary mitral regurgitation, transcatheter edge-to-edge repair can help delay heart transplantation or long-term MCS. In later stages, the appropriateness of heart transplantation should be evaluated, and the use of short- or long-term MCS may be considered. A multidisciplinary HF management program is crucial for patients with advanced HF. Recent treatment advances, including drugs, devices, and MCS, have broadened the options available to patients with advanced HF and this trend is expected to continue.

2-year outcomes of MitraClip as a bridge to heart transplantation: The international MitraBridge registry

BackgroundIn the first report from the MitraBridge registry, MitraClip as a bridge to heart transplantation (HTx) proved to be at 1-year an effective treatment strategy for 119 patients with advanced heart failure (HF) who were potential candidates for HTx. We aimed to determine if benefits of MitraClip procedure as a bridge-to-transplant persist up to 2-years. MethodsBy the end of the enrollment period, a total of 153 advanced HF patients (median age 59 years, left ventricular ejection fraction 26.9 ± 7.7%) with significant secondary mitral regurgitation, who were potential candidates for HTx and were treated with MitraClip as a bridge-to-transplant strategy, were included in the MitraBridge registry. The primary endpoint was the 2-year composite adverse events rate of all-cause death, first hospitalization for HF, urgent HTx or LVAD implantation. ResultsProcedural success was achieved in 89.5% of cases. Thirty-day mortality was 0%. At 2-year, Kaplan-Meier estimates of freedom from primary endpoint was 47%. Through 24 months, the annualized rate of HF rehospitalization per patient-year was 44%. After an overall median follow-up time of 26 (9–52) months, elective HTx was successfully performed in 30 cases (21%), 19 patients (13.5%) maintained or obtained the eligibility for transplant, and 32 patients (22.5%) no longer had an indication for HTx because of significant clinical improvement. ConclusionsAfter 2-years of follow-up, the use of MitraClip as a bridge-to-transplant was confirmed as an effective strategy, allowing elective HTx or eligibility for transplant in one third of patients, and no more need for transplantation in 22.5% of cases.

Identifying Patients With Secondary Mitral Regurgitation and Heart Failure who may Benefit From Transcatheter Edge-to-Edge Repair in the Wellington Region

As the New Zealand population ages, the incidence of heart failure and valvular disease increases. The Cardiovascular Outcomes Assessment of MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial showed decreased rates of hospitalisation for heart failure and all-cause mortality with transcatheter edge-to-edge repair (TEER) for clinically significant secondary mitral regurgitation (MR) within 24 months of follow-up compared with medical therapy. This retrospective observational study aimed to identify patients who may benefit from TEER in Wellington. This study retrospectively reviewed the electronic records of 337 consecutive patients aged ≥18 years who presented to Wellington Hospital from April to September 2022 with heart failure and identified those who met modified COAPT criteria: at least moderate secondary mitral regurgitation, left ventricular ejection fraction (LVEF) 20%–50% on echocardiography, and who did not meet criteria for cardiac surgery or other valve intervention. Forty patients met the modified COAPT criteria: 27 (68%) were male and 13 (33%) were female. The mean age was 71.7 years. Of them, 55% were New Zealand European, 23% were Pasifika, and 13% were New Zealand Māori. A total of 58% had moderate MR, 33% had moderate–severe MR, and 10% had severe MR; the median LVEF was 30%. The median survival was 309 days in those who met the modified COAPT criteria compared with 365 days in those who did not (non-statistically significant). Among patients who presented to Wellington Hospital with heart failure, a significant proportion (11.9%) had clinically significant secondary MR, who trend towards shorter survival times compared with those who present with heart failure in general. According to international guidelines and trial data such as COAPT, these patients would have potentially benefitted from TEER.

Association between triglyceride glucose index and worsening heart failure in significant secondary mitral regurgitation following percutaneous coronary intervention

BackgroundThe triglyceride glucose (TyG) index is an alternative to insulin resistance (IR) as an early indicator of worsening heart failure (HF). Patients with secondary mitral regurgitation (sMR) often experience progressive deterioration of cardiac function. This study aimed to investigate the relationship between the TyG index and worsening of HF in significant sMR (grade ≥ 2) following percutaneous coronary intervention (PCI).MethodsThis study enrolled participants with significant sMR following PCI from a multicenter cohort study. The patients were divided into the following 3 groups according to tertiles of TyG index: T1, TyG ≤ 8.51; T2, TyG > 8.51 to ≤ 8.98; and T3, TyG > 8.98. The main clinical outcome was worsening HF including unplanned rehospitalization or unscheduled physician office/emergency department visit due to HF and unplanned mitral valve surgery.ResultsA total of 922 patients (mean ± SD age, 64.1 ± 11.0 years; 79.6% male) were enrolled. The incidence of worsening HF was 15.5% in T1, 15.7% in T2, and 26.4% in T3. In the multivariable model, the highest TyG tertile (T3 group) was more strongly correlated with worsening HF than the lowest tertile (T1 group) after adjusting for confounders (adjusted hazard ratio, 2.44; 95% confidence interval, 1.59–3.72; P < 0.001). The addition of TyG to risk factors such as N-terminal pro brain natriuretic peptide and clinical models improved the predictive ability of TyG for worsening HF.ConclusionsElevated preprocedural TyG index is a significant and independent risk factor for worsening HF in sMR following PCI that can be used for risk stratification.

Prevalence and Prognostic Implications of Moderate or Severe Mitral Regurgitation in Patients with Bicuspid Aortic Valve

Significant (moderate or greater) mitral regurgitation (MR) could augment the hemodynamic effects of aortic valvular disease in patients with bicuspid aortic valve (BAV), imposing a greater hemodynamic burden on the left ventricle and atrium, possibly culminating in a faster onset of left ventricular dilation and/or symptoms. The aim of this study was to determine the prevalence and prognostic implications of significant MR in patients with BAV. In this large, multicenter, international registry, a total of 2,932 patients (mean age, 48±18years; 71% men) with BAV were identified. All patients were evaluated for the presence of significant primary or secondary MR by transthoracic echocardiography and were followed up for the end points of all-cause mortality and event-free survival. Overall, 147 patients (5.0%) had significant primary (1.5%) or secondary (3.5%) MR. Significant MR was associated with all-cause mortality (hazard ratio [HR], 2.80; 95% CI, 1.91-4.11; P<.001) and reduced event-free survival (HR, 1.97; 95% CI, 1.58-2.46; P<.001) on univariable analysis. MR was not associated with all-cause mortality (adjusted HR, 1.33; 95% CI, 0.85-2.07; P=.21) or event-free survival (adjusted HR, 1.10; 95% CI, 0.85-1.42; P=.49) after multivariable adjustment. However, sensitivity analyses demonstrated that significant MR not due to aortic valve disease retained an independent association with mortality (adjusted HR, 1.81; 95% CI, 1.04-3.15; P=.037). Subgroup analyses demonstrated an independent association between significant MR and all-cause mortality for individuals with significant aortic regurgitation (HR, 2.037; 95% CI, 1.025-4.049; P=.042), although this association was not observed for subgroups with significant aortic stenosis or without significant aortic valve dysfunction. Significant MR is uncommon in patients with BAV. Following adjustment for important confounding variables, significant MR was not associated with adverse prognosis in this large study of patients with BAV, except for the patient subgroup with moderate to severe aortic regurgitation. In addition, significant MR not due to aortic valve disease demonstrated an independent association with all-cause mortality.

Dynamic Secondary Mitral Regurgitation: Current Evidence and Challenges for the Future.

Heart failure (HF) is a challenging situation in healthcare worldwide. Secondary mitral regurgitation (SMR) is a common condition in HF patients with reduced ejection fraction (HFrEF) and tends to be increasingly associated with unfavorable clinical outcomes as the severity of SMR increases. It is worth noting that SMR can deteriorate dynamically under stress. Over the past three decades, the characteristics of dynamic SMR have been studied. Dynamic SMR contributes to the reduction in exercise capacity and adverse clinical outcomes. Current guidelines refer to the indication of transcatheter edge-to-edge repair (TEER) for significant SMR based on data from the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial if symptomatic despite optimal guideline-directed medical therapy (GDMT) and cardiac resynchronization therapy (CRT), but nonpharmacological treatment for dynamic SMR remains challenging. In HFrEF patients with LV dyssynchrony and dynamic SMR, CRT can improve LV dyssynchrony and subsequently attenuate SMR at rest and during exercise. Also, a recent study suggests that TEER with GDMT and CRT is more effective in symptomatic patients with HFrEF and dynamic SMR than GDMT and CRT alone. Further studies are needed to evaluate the safety and efficacy of nonpharmacological treatments for dynamic SMR. In this review, current evidence and challenges for the future of dynamic SMR are discussed.

Left Atrial Reservoir Function and Outcomes in Secondary Mitral Regurgitation

•LARS is associated with MR severity in patients with more than mild secondary MR.•LARS is associated with mortality in patients with more than mild secondary MR.•LARS provides incremental prognostic value over LA volume and LV GLS. BackgroundLeft atrial (LA) size is a marker of disease severity and is related to worse outcomes in secondary mitral regurgitation (MR). The prognostic value of LA function assessed by LA reservoir strain (LARS), however, remains unknown. The aim of this study was to investigate the prognostic implications of LARS in patients with significant secondary MR.MethodsLARS was evaluated using speckle-tracking echocardiography in patients with more than mild (grade ≥ 2) secondary MR. The population was divided into two groups according to the median LARS value (9.8%). The primary end point was all-cause mortality.ResultsA total of 666 patients (mean age, 66 ± 11 years; 68% men) were included. On multivariable analysis, more severe MR was independently associated with more impaired LARS (LARS < 9.8%; odds ratio, 0.419; 95% CI, 0.249-0.704; P = .001). During a median follow-up period of 5 years (interquartile range, 2-10), 383 patients (58%) died. Patients with LARS < 9.8% had significantly lower survival rates at 1-, 2-, and 5-year follow-up (85%, 70%, and 45%, respectively) compared with patients with LARS ≥ 9.8% (96%, 93%, and 78%, respectively; P < .001). After multivariable adjustment (including LA volume and left ventricular global longitudinal strain), more preserved LARS (≥9.8%; hazard ratio, 0.499; 95% CI, 0.386-0.645; P < .001) was independently associated with lower all-cause mortality. LARS provided incremental prognostic value over LA volume and left ventricular global longitudinal strain.ConclusionsLARS is independently associated with all-cause mortality in patients with significant secondary MR and has incremental prognostic value over LA volume and left ventricular global longitudinal strain. LARS may improve risk stratification of patients with secondary MR. Left atrial (LA) size is a marker of disease severity and is related to worse outcomes in secondary mitral regurgitation (MR). The prognostic value of LA function assessed by LA reservoir strain (LARS), however, remains unknown. The aim of this study was to investigate the prognostic implications of LARS in patients with significant secondary MR. LARS was evaluated using speckle-tracking echocardiography in patients with more than mild (grade ≥ 2) secondary MR. The population was divided into two groups according to the median LARS value (9.8%). The primary end point was all-cause mortality. A total of 666 patients (mean age, 66 ± 11 years; 68% men) were included. On multivariable analysis, more severe MR was independently associated with more impaired LARS (LARS < 9.8%; odds ratio, 0.419; 95% CI, 0.249-0.704; P = .001). During a median follow-up period of 5 years (interquartile range, 2-10), 383 patients (58%) died. Patients with LARS < 9.8% had significantly lower survival rates at 1-, 2-, and 5-year follow-up (85%, 70%, and 45%, respectively) compared with patients with LARS ≥ 9.8% (96%, 93%, and 78%, respectively; P < .001). After multivariable adjustment (including LA volume and left ventricular global longitudinal strain), more preserved LARS (≥9.8%; hazard ratio, 0.499; 95% CI, 0.386-0.645; P < .001) was independently associated with lower all-cause mortality. LARS provided incremental prognostic value over LA volume and left ventricular global longitudinal strain. LARS is independently associated with all-cause mortality in patients with significant secondary MR and has incremental prognostic value over LA volume and left ventricular global longitudinal strain. LARS may improve risk stratification of patients with secondary MR.

Extramitral Valvular Cardiac Involvement in Patients With Significant Secondary Mitral Regurgitation

Patients with secondary mitral regurgitation (SMR) often have extramitral valve cardiac involvement, which can influence the prognosis. SMR can be defined according to groups of extramitral valve cardiac involvement. The prognostic implications of such groups in patients with moderate and severe SMR (significant SMR) are unknown. A total of 325 patients with significant SMR were classified according to the extent of cardiac involvement on echocardiography: left ventricular involvement (group 1), left atrial involvement (group 2), tricuspid valve and pulmonary artery vasculature involvement (group 3), or right ventricular involvement (group 4). The primary end point was all-cause mortality. The prevalence of each cardiac involvement group was 17% in group 1, 12% in group 2, 23% in group 3%, and 48% in group 4. Group 3 and group 4 were independently associated with all-cause mortality (hazard ratio 1.794, 95% confidence interval 1.067 to 3.015, p=0.027 and hazard ratio 1.857, 95% confidence interval 1.145 to 3.012, p=0.012, respectively). In conclusion, progressive extramitral valve cardiac involvement (group 3 and group 4) was independently associated with all-cause mortality in patients with significant SMR.

Prognostic value of three dimensional-vena contracta area in patients with secondary mitral regurgitation

Abstract Background Effective regurgitant orifice area (EROA) is an important quantitative measurement for mitral regurgitation (MR) grading. Yet, the accuracy of this method is limited in patients with secondary mitral regurgitation (SMR). Three-dimensional (3D) color Doppler echocardiography allows for the direct assessment of the vena contracta area (VCA). The prognostic value of 3D-VCA in patients with secondary MR has not been investigated. Purpose The aim of the present study was to assess the association between 3D-VCA and prognosis of patients with SMR. Methods A total of 218 patients (69% men, median age 74 years) with significant SMR were retrospectively analyzed. 3D-VCA was measured offline with dedicated software, from restored 3D color Doppler full volume datasets of the mitral valve (Figure 1). The population was divided according to the American College of Cardiology expert recommendation for the grading of severe MR (VCA ≥50 mm2 and VCA &amp;lt;50 mm2). Patients were followed up for the combined end point of all-cause mortality or heart failure hospitalization. Results Of the total population, 63% had an ischemic etiology, 60% had atrial fibrillation and 25% cardiac resynchronization therapy. Patients with 3D-VCA ≥50 mm2 needed more diuretic therapy, had a larger left ventricle and atrium, and had more post-procedural residual MR. A total of 82% of patients underwent MitraClip device implantation, 17% had mitral valve repair and 1% had mitral valve replacement. During a median follow-up of 28 months, 130 (60%) met the combined end point (101 (46%) patients died and 81 (37%) were hospitalized due to heart failure). When dividing the population according to the cut-off of 3D-VCA, patients with a 3D-VCA≥50 mm2 had a worse prognosis compared with their counterparts (Figure 2). In a multivariable Cox regression analysis, 3D-VCA≥50 mm2 remained independently associated with the composite endpoint of all-cause mortality or heart failure hospitalization (HR=1.454, 95% CI 1.020–2.072, p=0.038). Conclusion In patients with SMR, a 3D-VCA ≥50 mm2 was independently associated with a combined endpoint of death or heart failure hospitalization. Funding Acknowledgement Type of funding sources: None. Figure 1. Method of 3D-VCA measurementFigure 2. Kaplan-Meier survival curve

Prevalence and prognostic implications of moderate or severe mitral regurgitation in patients with bicuspid aortic valve

Abstract Background Significant (≥ moderate) mitral regurgitation (MR) could augment the hemodynamic effects of aortic valvular disease in patients with bicuspid aortic valve (BAV), imposing a greater hemodynamic burden on left ventricle and atrium, possibly culminating in a faster onset of left ventricular (LV) dilation and/or symptoms. Purpose To determine the prevalence and prognostic implications of significant MR in patients with BAV. Methods In this large, multicenter, international registry, a total of 2,932 patients (48±18 years, 71% male) with BAV were identified. All patients were evaluated for the presence of significant primary or secondary MR by transthoracic echocardiography and were followed-up for the endpoint of all-cause mortality and a combined endpoint of all-cause mortality or aortic valve surgery. Results Overall, 147 patients (5.0%) had significant primary (1.5%) or secondary (3.5%) MR. Significant MR was associated with all-cause mortality (HR 2.80, 95% CI 1.91 to 4.11, p&amp;lt;0.001, Figure A) and reduced event-free survival (HR 1.97, 95% CI 1.58 to 2.46, p&amp;lt;0.001) on univariable analysis. However, MR was not associated with all-cause mortality (HR 1.33, 95% CI 0.85 to 2.07, p=0.21, Figure B) or event-free survival (HR 1.10, 95% CI 0.85 to 1.42, p=0.46) after multivariable adjustment. Subgroup analyses demonstrated an independent association between significant MR and all-cause mortality for individuals with significant aortic regurgitation (HR 2.04, 95% CI 1.03 to 4.05, p=0.042), although this association was not observed for subgroups with significant aortic stenosis or without significant aortic valve dysfunction. Conclusions Significant MR is uncommon in patients with BAV. Following adjustment for confounding variables, significant MR was not associated with event-free or overall survival. Funding Acknowledgement Type of funding sources: None. Survival curves for all-cause mortality

Sex differences in prognosis of significant secondary mitral regurgitation.

AimsSecondary mitral regurgitation (MR) is more frequent in men than in women. However, little is known about differences in prognosis between men and women with secondary MR. The objective of this study is to investigate the sex distribution of secondary MR and the prognostic differences between sexes.MethodsPatients with significant secondary MR, of both ischaemic and non‐ischaemic aetiologies, were identified through the departmental electronic patient files and retrospectively analysed. The primary endpoint was all‐cause mortality.ResultsA total of 698 patients (mean age 66 ± 11 years) with significant secondary MR were included: 471 (67%) men and 227 (33%) women. Ischaemic heart failure was significantly more common in men (61%), whereas non‐ischaemic heart failure was more prevalent in women (63%). Women had significantly smaller left ventricular (LV) volumes when compared with men and more preserved LV systolic function when assessed with LV global longitudinal strain (GLS; 8.5 ± 4.1% vs. 7.5 ± 3.6%; P = 0.004). Women more often underwent surgical mitral valve repair (34%) when compared with men (26%), although no differences were observed for transcatheter mitral valve repair. During a median follow‐up of 57 [interquartile range 29–110] months, 373 (53%) patients died. Women showed significantly lower mortality rates at 1‐, 2‐ and 5‐year follow‐up (9%, 16% and 33% vs. 10%, 20% and 42%) when compared with men (P = 0.001).ConclusionsSignificant secondary MR is more frequently observed in men as compared with women and is associated with worse prognosis.

Prognostic Value of Pre-operative Atrial Fibrillation in Patients With Secondary Mitral Regurgitation Undergoing MitraClip Implantation

Limited data are available regarding the independent prognostic role of preoperative atrial fibrillation (AF) after transcatheter mitral valve repair with MitraClip. We sought to evaluate the impact of preoperative AF in patients with heart failure (HF) and concomitant secondary mitral regurgitation (MR) after MitraClip treatment. The study included 605 patients with significant secondary MR from a multicenter international registry. Patients were stratified into 2 groups according to the presence or absence of preoperative AF. Primary end point was 5-year overall death, secondary end points were 5-year cardiac death and first re-hospitalization for HF. To account for baseline differences, patients were propensity score matched 1:1. The overall prevalence of preoperative AF was 44%. At 5-year Kaplan-Meier analysis, compared with patients without AF, those with AF had significantly more adverse events in term of overall death (67% vs 43%; HR 1.84, log-rank p <0.001) and cardiac death (56% vs 29%; HR 2.11, log-rank p <0.001) and re-hospitalization for HF (63% vs 52%; HR 1.33, log-rank p = 0.048). Multivariate analysis identified AF as independent predictor of worse outcome in term of primary end point (HR 1.729, 95% C.I. 1.060 to 2.821; p = 0.028). After propensity score matching, patients with AF had higher rates of death and cardiac mortality but similar rates of re-hospitalization for HF. In conclusion, in patients with HF undergoing MitraClip treatment for secondary MR, preoperative AF is common and an unfavourable predictor of 5-year death and cardiac death. However, AF did not affect the frequency of re-hospitalization for HF.

Transcatheter Mitral Valve Repair in Patients with Heart Failure: A Meta-Analysis

Background: Severe secondary mitral regurgitation (MR) is associated with poor prognosis in heart failure patients with left ventricular systolic dysfunction. Few observational and randomized controlled studies demonstrated the efficacy of transcatheter mitral valve repair in heart failure patients with significant MR. A meta-analysis of published studies was performed to evaluate the role of transcatheter mitral valve repair using the MitraClip device in heart failure patients with significant secondary MR. Methods: A literature search was performed using PubMed, Cochran CENTRAL, and Embase databases using the search terms “percutaneous mitral valve repair” or “transcatheter mitral valve repair” and “heart failure.” Studies that compared medical therapy plus transcatheter mitral valve repair using MitraClip to medical therapy alone in heart failure patients with significant secondary MR were included for pooled analysis. A random-effects model with the Mantel-Haenszel method was used to analyze the data. Results: Four studies, 2 randomized controlled and 2 nonrandomized studies met the criteria for analysis. Pooled analysis included a total of 1,421 patients, of which 746 patients underwent transcatheter mitral valve repair and 675 patients received medical therapy alone. When compared to medical therapy, transcatheter mitral valve repair significantly decreased all-cause mortality (OR 0.58, 95% CI 0.37–0.91; p = 0.02). A trend toward significant reduction in rehospitalizations (OR 0.35, 95% CI 0.12–1.00; p = 0.05) was also observed. Periprocedural complications ranged from 7.5 to 12.6%. Conclusion: Evidence from pooled analysis suggests that transcatheter mitral valve repair using MitraClip on top of medical therapy, in appropriately selected symptomatic heart failure patients with significant secondary MR, provides survival benefit and may decrease hospitalizations when compared with guideline-directed medical therapy alone.

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

Prognostic Value of Left Ventricular Global Longitudinal Strain in Patients With Secondary Mitral Regurgitation

BackgroundLeft ventricular (LV) systolic function may be overestimated in patients with secondary mitral regurgitation (MR) when using LV ejection fraction (EF). LV global longitudinal strain (GLS) is a less load-dependent measure of LV function. However, the prognostic value of LV GLS in secondary MR has not been evaluated. ObjectivesThis study sought to demonstrate the prognostic value of LV GLS over LVEF in patients with secondary MR. MethodsA total of 650 patients (mean 66 ± 11 years of age, 68% men) with significant secondary MR were included. The study population was subdivided based on the LV GLS value at which the hazard ratio (HR) for all-cause mortality was >1 using a spline curve analysis (LV GLS <7.0%, impaired LV systolic function vs. LV GLS ≥7.0%, preserved LV systolic function). The primary endpoint was all-cause mortality. ResultsDuring a median follow-up of 56 (interquartile range: 28 to 106 months) months, 334 (51%) patients died. Patients with a more impaired LV GLS showed significantly higher mortality rates at 1-, 2-, and 5-year follow-up (13%, 23%, and 44%, respectively) when compared with patients with more preserved LV systolic function (5%, 14%, and 31%, respectively). On multivariable analysis, LV GLS <7.0% was associated with increased mortality (HR: 1.337; 95% confidence interval: 1.038 to 1.722; p = 0.024), whereas LVEF ≤30% was not (HR: 1.055; 95% confidence interval: 0.794 to 1.403; p = 0.711). ConclusionsIn patients with secondary MR, impaired LV GLS was independently associated with an increased risk for all-cause mortality, whereas LVEF was not. LV GLS may therefore be useful in the risk stratification of patients with secondary MR.

5942Clinical outcomes and prognostic implications of effective regurgitant orifice area. Defining severe mitral regurgitation

Abstract Background Previous studies showed that the effective regurgitant orifice area (EROA) is a strong predictor of clinical outcomes. However, there is controversy over the optimal threshold that identifies patients at high-risk, especially in secondary mitral regurgitation (MR). Purpose To determine the optimal EROA threshold that identifies a subgroup patients with an increased risk of cardiac death and hospitalization for heart failure (HF), in both, primary and secondary MR. Methods A total of 6022 consecutive transthoracic echocardiograpic studies were analysed. Patients with significant MR were prospectively included. The EROA was calculated by the PISA method. Each patient was followed up for three years. Cox regression was performed to study predictors of the combined end-point. ROC curve analysis was performed to determine the optimal cut-off values of EROA. Results Significant primary MR was found in 115 patients (62%), whereas significant secondary MR was described in 71 studies (38%). In primary MR, the optimal threshold of EROA for predicting the combined end-point was 45mm2 (Sn=85.7%; Sp=82.2%). After adjusting for NYHA class, ejection fraction and chronic kidney disease, an EROA ≥45mm2 was strongly associated with cardiac death and admissions due to HF (HR 15.65, 95% CI 4.34–56.47, p&lt;0.001). Regarding secondary MR, the optimal cut-off value was 21mm2 (Sn=75.0%; Sp=61.8%) and the adjusted HR was 2.57 (95% CI 1.03–6.37, p=0.042). Sensitivity and specificity curves Conclusions Our study demonstrates that an EROA of at least 45mm2 in primary MR or of at least 21mm2 in secondary MR is independently associated with a significantly increased risk of cardiac death and hospitalization for HF.

Transcatheter Clip for Heart Failure with Mitral Regurgitation

Patients with heart failure and clinically significant secondary mitral regurgitation (MR) have poor prognoses, but the 2018 COAPT trial suggests that