Functional Mitral Regurgitation In Patients Research Articles

Relationship between the severity of functional mitral regurgitation at admission and one-year outcomes in patients hospitalized for acute heart failure with mildly reduced ejection fraction

BackgroundThe epidemiological distribution of functional mitral regurgitation (FMR) in heart failure (HF) and mildly reduced ejection fraction (HFmrEF) patients and its impact on outcomes remains unclear. We attempt to investigate the prognosis of FMR in patients with HFmrEF.MethodsThe HF center registry study is a prospective, single, observational study conducted at the Second Affiliated Hospital of Shenzhen University, where 2330 patients with acute HF (AHF) were enrolled and 890 HFmrEF patients were included in the analysis. The patients were stratified into three categories based on the severity of FMR: none/mild, moderate, and moderate-to-severe/severe groups. Subsequently, a comparison of the clinical characteristics among these groups was conducted, along with an assessment of the incidence of the primary endpoint (comprising all-cause mortality and readmission for HF) during a one-year follow-up period.ResultsThe one-year follow-up results indicated that the primary composite endpoint occurrence rates in the three groups were 23.5%, 32.9%, and 36.5%, respectively. The all-cause mortality rates in the three groups were 9.3%, 13.7%, and 16.4% respectively. Survival analysis demonstrated a statistically significant difference in the occurrence rates of the primary composite endpoint and all-cause mortality among the three groups (P < 0.05). Multifactor Cox regression revealed that moderate FMR and moderate-to-severe/severe FMR were independent risk factors for adverse clinical prognosis in HFmrEF patients, with hazard ratios and 95% confidence intervals of 1.382 (1.020–1.872, P = 0.037) and 1.546 (1.092–2.190, P = 0.014) respectively.ConclusionsModerate FMR and moderate-to-severe/severe FMR independently predict an unfavorable prognosis in patients with HFmrEF.

Percutaneous repair of moderate-to-severe or severe functional mitral regurgitation in patients with symptomatic heart failure: Baseline characteristics of patients in the RESHAPE-HF2 trial and comparison to COAPT and MITRA-FR trials.

The RESHAPE-HF2 trial is designed to assess the efficacy and safety of the MitraClip device system for the treatment of clinically important functional mitral regurgitation (FMR) in patients with heart failure (HF). This report describes the baseline characteristics of patients enrolled in the RESHAPE-HF2 trial compared to those enrolled in the COAPT and MITRA-FR trials. The RESHAPE-HF2 study is an investigator-initiated, prospective, randomized, multicentre trial including patients with symptomatic HF, a left ventricular ejection fraction (LVEF) between 20% and 50% with moderate-to-severe or severe FMR, for whom isolated mitral valve surgery was not recommended. Patients were randomized 1:1 to a strategy of delivering or withholding MitraClip. Of 506 patients randomized, the mean age of the patients was 70 ± 10 years, and 99 of them (20%) were women. The median EuroSCORE II was 5.3 (2.8-9.0) and median plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 2745 (1407-5385) pg/ml. Most patients were prescribed beta-blockers (96%), diuretics (96%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (82%) and mineralocorticoid receptor antagonists (82%). The use of sodium-glucose cotransporter 2 inhibitors was rare (7%). Cardiac resynchronization therapy (CRT) devices had been previously implanted in 29% of patients. Mean LVEF, left ventricular end-diastolic volume and effective regurgitant orifice area (EROA) were 31 ± 8%, 211 ± 76 ml and 0.25 ± 0.08 cm2, respectively, whereas 44% of patients had mitral regurgitation severity of grade 4+. Compared to patients enrolled in COAPT and MITRA-FR, those enrolled in RESHAPE-HF2 were less likely to have mitral regurgitation grade 4+ and, on average, HAD lower EROA, and plasma NT-proBNP and higher estimated glomerular filtration rate, but otherwise had similar age, comorbidities, CRT therapy and LVEF. Patients enrolled in RESHAPE-HF2 represent a third distinct population where MitraClip was tested in, that is one mainly comprising of patients with moderate-to-severe FMR instead of only severe FMR, as enrolled in the COAPT and MITRA-FR trials. The results of RESHAPE-HF2 will provide crucial insights regarding broader application of the transcatheter edge-to-edge repair procedure in clinical practice.

Abstract 17540: Functional Mitral Regurgitation is Associated With Decreased Papillary Muscle Viability Patients With Non-Ischemic Dilated Cardiomyopathy

Background: The underlying mechanisms of functional mitral regurgitation (FMR) in non-ischemic cardiomyopathy (NICM) are incompletely understood. Aims: We investigated the correlation between papillary muscle viability and FMR in NICM. Methods: We enrolled 66 patients with NICM (LVEF&lt;40%, NHYA III) undergoing CD34 + cell transplantation. At baseline, patients underwent electroanatomical mapping; papillary muscle viability was quantified by local unipolar voltage (UV) measurement, and decreased viability was defined as UV&lt;8.3 mV. All patients received granulocyte-colony stimulating factor; CD34 + cells were collected by apheresis and delivered by transendocardial injections. Echocardiography was performed at baseline and 6 months after cell therapy; severity of FMR was graded by multi-parametric approach. FMR improvement was defined as a reduction in FMR by ≥1 grade when compared to baseline. Results: At baseline, papillary muscle viability was decreased in 24 (36%) and preserved in 42 (64%) of patients. Moderate to severe (2-3+) FMR was more common in patients with decreased papillary muscle viability (6/24; 25%) than in patients with preserved viability (2/42; 5%, P=0.015). Transendocardial cell injections were performed in the papillary muscle area in 26 patients (Group A) and in other areas of the left ventricle in 40 patients (Group B). The groups did not differ in age (56±11 years in Group A vs. 54±10 years in Group B, P=0.32), sex (male: 96% vs. 85%, P=0.21), creatinine (0.98±0.27 mg/dL vs. 0.96±0.28 mg/dL, P=0.92), bilirubin (0.89±0.37 mg/dL vs. 0.92±0.35 mg/dL, P=0.45), LVEF (34±9% vs. 31±7%, P=0.12), NT-proBNP levels (1196±994 pg/mL vs. 1077±1176 pg/mL, P=0.68), the degree of FMR (1.28±0.78 vs. 1.02±0.38, P=0.20), or papillary muscle viability (9.9±3.0 mV vs. 10.3±3.2 mV, P=0.62). At 6 months after cell injection, FMR improved in 77% of patients in Group A vs. 13% in Group B (P=0.001). On multivariate analysis, cell injection in the papillary muscle area was an independent correlate of FMR improvement (P=0.01). Conclusions: FMR in patients with NICM is associated with decreased papillary muscle viability. Transendocardial injection of CD34 + cells in the papillary muscle area may improve FMR in this patient population.

Prevalence, mechanisms, and prognostic impact of dynamic mitral regurgitation assessed by isometric handgrip exercise.

The extent of mitral regurgitation (MR) may vary depending on the haemodynamic situation; thus, exercise testing plays an important role in assessing the haemodynamic relevance of MR. We aim to assess prevalence, mechanisms, and prognostic impact of exercise-induced changes in MR in patients with degenerative MR (DegMR) and functional MR (FMR). We enrolled 367 patients with at least mild MR who underwent standardized echocardiography at rest and during handgrip exercise. Handgrip exercise led to an increase in MR by one grade or more in 19% of DegMR and 28% of FMR patients. In FMR, patients with exercise-induced increases in MR, handgrip exercise led to a reduction in left ventricular stroke volume index, being maintained in DegMR patients. Exercise-induced changes in systolic pulmonary artery pressure were linked to changes in effective regurgitant orifice area (DegMR: r = 0.456; P < 0.001; FMR: r = 0.326; P < 0.001). Thus, 26% of patients with DegMR and FMR developed pulmonary hypertension during exercise. In both cohorts, a significant proportion of patients with non-severe MR at rest and exercise-induced severe MR underwent mitral valve surgery/intervention during follow-up. In FMR patients (but not in DegMR patients), early mitral valve surgery/intervention was independently associated with lower event rates during follow-up [0.177 (0.027-0.643); P = 0.025]. Handgrip exercise echocardiography provides important information regarding the dynamic nature of MR, exercise-induced changes in left ventricular function, and pulmonary circulation with subsequent consequences for further therapeutic decision making. Thus, it should be considered as a diagnostic tool in symptomatic patients with non-severe MR at rest.

Association Between Catheter Ablation for Nonparoxysmal Atrial Fibrillation and Functional Mitral Regurgitation in Patients With Heart Failure With Preserved Ejection Fraction

Functional mitral regurgitation (FMR) often coexists with atrial fibrillation (AF) and may have a causal relation with AF persistence and exacerbation of heart failure (HF). The purpose of this study was to investigate the impact of FMR on AF catheter ablation (AFCA) outcomes and improvement in FMR after AFCA in patients with HF with preserved ejection fraction (HFpEF) and nonparoxysmal AF. Excluding patients with primary valve disease or post-mitral valve repair, 280 patients with HFpEF who underwent CA for nonparoxysmal AF were retrospectively included. All patients completed 1-year follow-up and were assessed for FMR, AF recurrence and HF parameters, including echocardiography. At baseline, FMR was present in 153 (54.6%) patients (mild, n=112; moderate, n=40; severe, n=1), and these were decreased to 70 (25%) significantly 1year after AFCA (mild, n=64; moderate, n=6), 119 patients (78%) had improvement in MR (a decrease of ≥1 level in the severity from baseline to 1year on echocardiography). Overall, 274 patients (97.9%) had sinus rhythm at the 1-year examination, and recurrent AF-free survival did not differ in patients with and without MR improvement (83.2% vs 82.4%, p=0.908). However, the MR improvement group had a significantly lower cardiothoracic ratio, left atrial diameter, E/e', and B-type natriuretic peptide levels after 1year than those in the MR nonimprovement group. In conclusion, the majority of the HFpEF patients with nonparoxysmal AF had improvement of FMR after AFCA with the high maintenance of sinus rhythm, leading to a virtuous cycle of cardiac function.

Assessment of mitral valve geometry in nonvalvular atrial fibrillation patients with or without ventricular dysfunction: insights from high volume rate three-dimensional transesophageal echocardiography

Meticulous understanding of the mechanisms underpinning mitral regurgitation in atrial fibrillation (AF) patients is crucial to optimize therapeutic strategies. The morphologic characteristics of mitral valves in atrial functional mitral regurgitation (FMR) patients with and without left ventricular (LV) dysfunction were evaluated by high volume rate (HVR) three-dimensional transesophageal echocardiography (3D-TEE). In our study, 68 of 265 AF patients who underwent 3D-TEE were selected, including 36 patients with AF, FMR, and preserved LV function (AFMR group) and 32 patients with AF, FMR, and LV dysfunction (VFMR group). In addition, 36 fever patients without heart disease were included in the control group. Group comparisons were performed by one-way analysis of variance for continuous variables. The left atrium (LA) was enlarged in the AFMR and VFMR groups compared with the control group. The mitral annulus (MA) in the AFMR group was enlarged and flattened compared with the control group and was smaller than in the VFMR group. The annulus area fraction was significantly diminished in the AFMR and VFMR groups, indicative of reduced MA contractility. The posterior mitral leaflet (PML) angle was smallest in the AFMR group and largest in the control group, whereas the distal anterior mitral leaflet angle did not significantly differ among the three groups. LA remodeling causes expansion of the MA and reduced MA contractility, disruption of the annular saddle shape, and atriogenic PML tethering. Comparison of atrial FMR patients with and without LV dysfunction indicates that atriogenic PML tethering is an important factor that aggravates FMR. HVR 3D-TEE improves the 3D temporal resolution greatly.

Incidence, risk factors, and outcomes of atrial functional mitral regurgitation in patients with atrial fibrillation or sinus rhythm.

Atrial functional mitral regurgitation (AFMR) has been associated with atrial fibrillation (AF) and heart failure with preserved ejection fraction. However, data on incident AFMR are scarce. We aimed to study the incidence, risk factors, and clinical significance of AFMR in AF or sinus rhythm (SR). Adults with new diagnosis of AF and adults in SR were identified. Patients with >mild MR at baseline, primary mitral disease, cardiomyopathy, left-sided valve disease, previous cardiac surgery, or with no follow-up echocardiogram were excluded. Diastolic dysfunction (DD) was indicated by ≥2/4 abnormal diastolic function parameters [mitral medial e', mitral medial E/e', tricuspid regurgitation velocity, left atrial volume index (LAVI)]. Overall, 1747 patients with AF and 29 623 in SR were included. Incidence rate of >mild AFMR was 2.6 per 100 person-year in new-onset AF and 0.7 per 100 person-year in SR, P < 0.001. AF remained associated with AFMR in a propensity score-matched analysis based on age, sex, and comorbidities between AF and SR [hazard ratio: 3.80 (95% confidence interval 3.04-4.76)]. Independent risk factors associated with incident AFMR were age ≥65 years, female sex, LAVI, and DD in both AF and SR, in addition to rate (vs. rhythm) control in AF. Incident AFMR was independently associated with all-cause death in both groups (both P < 0.001). AF conferred a three-fold increase in the risk of incident AFMR. DD, older age, left atrial size, and female sex were independent risk factors in both SR and AF, while rhythm control was protective. AFMR was universally associated with worse mortality.

Determinants of disproportionate functional mitral regurgitation

Abstract Funding Acknowledgements Type of funding sources: None. Background Recent studies have suggested that "disproportionate" functional mitral regurgitation (FMR) defined by greater MR than expected from the degree of left ventricular (LV) dilatation may be a good candidate for transcatheter edge-to-edge repair (TEER). Determinants of disproportionate FMR (d-FMR) is unknown. We hypothesized that additional factors such as asymmetric tethering, extreme mitral annular dilatation, and deep indentation, might worsen the severity of FMR regardless of LV volumes and lead to d-FMR. Purpose To investigate the impact of the additional factors on the proportionality of FMR. Methods We reviewed consecutive FMR patients who underwent TEER and 3D transesophageal echocardiography (3DTEE) in our institute between 2018 and 2022. d-FMR and proportionate FMR (p-FMR) were defined by the effective regurgitant orifice area (EROA)/LV end-diastolic volume (LVEDV) &amp;gt;0.2 and ≤0.2 mm2/mL, respectively. Results A total of 110 FMR patients (63 d-FMR and 47 p-FMR, 75±12 years old, 46.3% female) were included. Patients with d-FMR had significantly larger EROA than p-FMR (41 ± 12 vs 33 ± 11 mm2, P&amp;lt;0.001) despite smaller LVEDV index (100 ± 28 vs 138 ± 49 mL/m2, P&amp;lt;0.001), better LV ejection fraction (37 ± 10% vs 27 ± 8%, P&amp;lt;0.001), and lower tenting height (7.6 ±2.9 vs 9.4 ± 2.7 mm, P=0.009). The 3DTEE analysis revealed that patients with d-FMR were more likely to have asymmetric tethering (29% vs 21%), extreme mitral annular dilatation (&amp;gt;700 mm2/m2; 54% vs 30%), and deep indentation (22% vs 4.3%) The presence of such additional factors was independently associated with d-FMR (odds ratio 3.83, P=0.0081) after adjustment by body surface area and LVEDV index. Furthermore, EROA/LVEDV increased as the number of additional factors increased. (Jonckheere-Terpstra test, P&amp;lt;0.001). TEER successfully reduced FMR regardless of the presence of such additional factor (success rate 95% vs. 96%, P&amp;gt;0.99). Conclusions The presence of additional factors exacerbates MR independently of LV size and is an important mechanism of d-FMR. TEER is an effective therapy to reduce FMR regardless of these factors.

Transcatheter edge-to-edge repair for chronic functional mitral regurgitation in patients with very severe left ventricular dysfunction

There is scarce data on transcatheter edge-to-edge repair (TEER) for chronic functional mitral regurgitation (FMR) in the setting of very severe left ventricular dysfunction (LVD), defined by a left ventricular ejection fraction (LVEF) of <20%. We retrospectively explored periprocedural characteristics and one-year clinical and echocardiographic outcomes of consecutive patients with chronic FMR and very severe LVD who underwent an isolated, first-time TEER. The composite of all-cause mortality or heart failure hospitalizations constituted the primary outcome. Ninety-six patients (median age 69 [IQR, 55-76] years, 64 (66.7%) males, median LVEF 15 [IQR, 12-17] %) were included. In 47 (49.0%), TEER was performed urgently or in the setting of hemodynamic instability. Almost all procedures (98.0%) were technically successful, leading to ≤moderate MR in 94.7% and 90.7% of cases by 1-month and 1-year, respectively. New York Heart Association class ≤II was maintained in 60.0% of patients. One-year survival and freedom from the primary outcome were 74.0% and 50.0%, respectively. Functional and echocardiographic improvement compared to baseline was independent of procedural urgency, hemodynamic stability, and downstream left ventricular assist device implantation / heart transplantation (n=12). Mortality was not predicted by COAPT exclusion criteria, nor was the primary outcome discriminated by published risk models. TEER for chronic FMR is feasible, safe, and efficacious in selected patients with very severe LVD. Preprocedural risk stratification in this population may be optimized.

Atrial functional mitral regurgitation in patients with paroxysmal and persistent atrial fibrillation

Atrial functional mitral regurgitation in patients with paroxysmal and persistent atrial fibrillation

Improved mid-term stability of MR reduction with an increased number of clips after percutaneous mitral valve repair in functional MR.

Percutaneous mitral valve repair (PMVR) has evolved to be a standard procedure in suitable patients with mitral regurgitation (MR) not accessible for open surgery. Here, we analyzed the influence of the number and positioning of the clips implanted during the procedure on MR reduction analyzing also sub-collectives of functional and degenerative MR (DMR). We included 410 patients with severe MR undergoing PMVR using the MitraClip® System. MR and reduction of MR were analyzed by TEE at the beginning and at the end of the PMVR procedure. To specify the clip localization, we sub-divided segment 2 into 3 sub-segments using the segmental classification of the mitral valve. We found an enhanced reduction of MR predominantly in DMR patients who received more than one clip. Implantation of only one clip led to a higher MR reduction in patients with functional MR (FMR) in comparison to patients with DMR. No significant differences concerning pressure gradients could be observed in degenerative MR patients regardless of the number of clips implanted. A deterioration of half a grade of the achieved MR reduction was observed 6months post-PMVR independent of the number of implanted clips with a better stability in FMR patients, who got 3 clips compared to patients with only one clip. In patients with FMR, after 6months the reduction of MR was more stable with an increased number of implanted clips, which suggests that this specific patient collective may benefit from a higher number of clips.

Racial disparities in characteristics and outcomes of patients undergoing mitral transcatheter edge-to-edge repair

There are scarce data regarding the post-mitral transcatheter edge-to-edger repair (TEER) course in different racial groups. To assess the impact of race on outcomes following TEER for mitral regurgitation (MR). This is a single-center, retrospective analysis of consecutive TEER procedures performed during 2013-2020. The primary outcome was the composite of all-cause mortality or heart failure (HF) hospitalizations along the first postprocedural year. Secondary outcomes included individual components of the primary outcome, New York Heart Association (NYHA) class, MR grade, and left ventricular mass index (LVMi). Out of 964 cases, 751 (77.9%), 88 (9.1%), 68 (7.1%), and 57 (5.9%) were whites, blacks, Asians, and Hispanics, respectively. At baseline, non-whites and blacks were younger and more likely be female, based in lower socioeconomic areas, not fully insured, diagnosed with functional MR, and affected by biventricular dysfunction. Intra-procedurally, more devices were implanted in blacks. At 1-year, non-whites (vs. whites) and blacks (vs. non-blacks or whites) experienced higher cumulative incidence of the primary outcome (32.9% vs. 22.5%, p = 0.002 and 38.6% vs. 23.4% or 22.5%, p = 0.002 or p = 0.001, respectively), which were accounted for by hospitalizations in the functional MR sub-cohort (n = 494). NYHA class improved less among blacks with functional MR. MR severity and LVMi equally regressed in all groups. White race (HR 0.62, 95% CI 0.39-0.99, p = 0.047) and black race (HR 2.07, 95% CI 1.28-3.35, p = 0.003) were independently associated with the primary outcome in functional MR patients only. Mitral TEER patients of different racial backgrounds exhibit major differences in baseline characteristics. Among those with functional MR, non-whites and blacks also experience a less favorable 1-year clinical outcome.

Anatomical Changes after Transcatheter Edge-to-Edge Repair in Functional MR According to MitraClip Generation

The use of mitral transcatheter edge-to-edge repair (TEER) is rapidly increasing. Anatomical changes have been described after TEER with the MitraClip system in patients with functional mitral regurgitation (MR), although no study has yet evaluated such anatomical impacts in patients treated with the G4 MitraClip generation. This research constituted a prospective, single-center, observational study including consecutive patients with functional MR. Mitral three-dimensional images were obtained transesophageally with echocardiography before and immediately after TEER. Patients receiving the late-generation (G4) system were compared to those receiving early-generation systems. A total of 116 functional MR patients were evaluated, and 40 (34.5%) and 76 (65.5%) received a late-generation (G4) or early-generation device system, respectively. The baseline clinical and echocardiographic features were well-balanced between the groups. Overall, there was a significant reduction in mitral annular size after the intervention, and greater reductions in the anteroposterior diameter (4 mm vs. 3.54 mm, p = 0.03), annular perimeter (11.07 mm vs. 5.29 mm for 3D-perimeter, p = 0.001), and annular area (1.29 cm2 vs. 1.03 cm2, p = 0.002) were found for patients receiving the late G4 device generation compared to the early-generation systems. In patients with functional MR, we observed significant changes in mitral valve anatomy with a reduction in anteroposterior diameter, valve perimeter, and area. In our cohort, the extent of those changes was greater with the use of the new-generation G4 MitraClip system compared to prior device generations.

Comparison of transcatheter edge-to-edge and surgical repair in patients with functional mitral regurgitation using a meta-analytic approach.

Evidence regarding favorable treatment of patients with functional mitral regurgitation (FMR) using transcatheter edge-to-edge repair (TEER) is constantly growing. However, there is only few data directly comparing TEER and surgical mitral valve repair (SMVr). To compare baseline characteristics, short-term and 1-year outcomes in FMR patients undergoing mitral valve (MV) TEER or SMVr using a meta-analytic approach. Systematic database search identified 1,703 studies reporting on TEER or SMVr for treatment of FMR between January 2010 and December 2020. A meta-analytic approach was used to compare outcomes from single-arm and randomized studies based on measures by means of their corresponding 95% confidence intervals (CI). Statistical significance was assumed if CIs did not overlap. A total of 21 TEER and 37 SMVr studies comprising 4,304 and 3,983 patients were included. Patients in the TEER cohort presented with higher age (72.0 ± 1.7 vs. 64.7 ± 4.7 years, p < 0.001), greater burden of comorbidities like hypertension (p < 0.001), atrial fibrillation (p < 0.001), lung disease (p < 0.001) and chronic renal disease (p = 0.005) as well as poorer left ventricular ejection fraction (30.9 ± 5.7 vs. 36.6 ± 5.3%, p < 0.001). In-hospital mortality was significantly lower with TEER [3% (95%-CI 0.02-0.03) vs. 5% (95%-CI 0.04-0.07)] and 1-year mortality did not differ significantly [18% (95%-CI 0.15-0.21) vs. 11% (0.07-0.18)]. NYHA [1.06 (95%-CI 0.87-1.26) vs. 1.15 (0.74-1.56)] and MR reduction [1.74 (95%-CI 1.52-1.97) vs. 2.08 (1.57-2.59)] were comparable between both cohorts. Despite considerably higher age and comorbidity burden, in-hospital mortality was significantly lower in FMR patients treated with TEER, whereas a tendency toward increased 1-year mortality was observed in this high-risk population. In terms of functional status and MR grade reduction, comparable 1-year results were achieved.

Abstract 12382: The Significance of Cardiac Resynchronization Therapy in Eligible Patients Undergoing Transcatheter Edge-to-Edge Repair for Functional Mitral Regurgitation

Introduction: Current guidelines prioritize the utilization of cardiac resynchronization therapy (CRT) over transcatheter edge-to-edge repair (TEER) in eligible patients with functional mitral regurgitation (FMR). However, the data in support of this recommendation are limited. Objective: To examine the effect of performing TEER for FMR in patients without prior CRT. Methods: This is a single-center, retrospective analysis encompassing 440 days (IQR, 135-915 days) of follow-up after TEER for FMR in patients who fulfilled guideline criteria for CRT. The study cohort was divided according to CRT status prior to the procedure. The primary outcome was the composite of all-cause mortality and heart failure hospitalization at one year. Secondary outcomes included components of the primary outcome, as well as 1-year all-cause hospitalization, and 1-month MR severity, indexed left atrial volume, and indexed left ventricular mass. Results: A total of 126 patients were included in the analysis, of whom 70 (56%) did not have CRT at the time of TEER. Baseline characteristics and immediate procedural success were mostly comparable between those with and those without CRT. The no-CRT group experienced higher rates of the primary outcome (43% vs 25%, p=0.041), which were accounted for by increased mortality (26% vs 11%, p=0.033). After multivariate analysis, the absence of CRT was associated with more than twice the risk of the primary outcome (HR 2.36, 95% CI 1.1-4.98, p=0.024). Secondary endpoints did not differ between the groups. Conclusions: In CRT eligible patients undergoing mitral TEER for FMR, 1-year outcome is less favorable when the procedure is not preceded by CRT.

Metabolomics implicate eicosanoids in severe functional mitral regurgitation.

Secondary, or functional, mitral regurgitation (FMR) was recently recognized as a separate clinical entity, complicating heart failure with reduced ejection fraction (HFrEF) and entailing particularly poor outcome. Currently, there is a lack of targeted therapies for FMR due to the fact that pathomechanisms leading to FMR progression are incompletely understood. In this study, we sought to perform metabolomic profiling of HFrEF patients with severe FMR, comparing results to patients with no or mild FMR. Targeted plasma metabolomics and untargeted eicosanoid analyses were performed in samples drawn from HFrEF patients (n=80) on optimal guideline-directed medical therapy. Specifically, 17 eicosanoids and 188 metabolites were analysed. Forty-seven patients (58.8%) had severe FMR, and 33 patients (41.2%) had no or non-severe FMR. Comparison of eicosanoid levels between groups, accounting for age, body mass index, and sex, revealed significant up-regulation of six eicosanoids (11,12-EET, 13(R)-HODE, 12(S)-HETE, 8,9-DiHETrE, metPGJ2, and 20-HDoHE) in severe FMR patients. Metabolites did not differ significantly. In patients with severe FMR, but not in those without severe FMR, levels of 8,9-DiHETrE above a cut-off specified by receiver-operating characteristic analysis independently predicted all-cause mortality after a median follow-up of 43 [interquartile range 38, 48] months [hazard ratio 12.488 (95% confidence interval 3.835-40.666), P<0.0001]. We report the up-regulation of various eicosanoids in patients with severe FMR, with 8,9-DiHETrE appearing to predict mortality. Our observations may serve as a nucleus for further investigations into the causes and consequences of metabolic derangements in this important valvular abnormality.

Effect of Impella 5.5 on Preexisting Functional Mitral Regurgitation in Patients with Heart Failure–Related Cardiogenic Shock

BackgroundHeart failure–related cardiogenic shock (HF-CS) is increasingly common. Moderate/severe functional mitral regurgitation (FMR) is commonly seen in patients presenting with decompensated heart failure and is associated with worse outcomes. Percutaneous mechanical circulatory support devices are increasingly used to provide hemodynamic support for ongoing CS. There is no description of the impact of Impella device on hemodynamic response when used in combination with preexisting FMR. MethodsRetrospective review of patients aged ≥18 years, who underwent Impella 5.5 implant for HF-CS, and who had a transthoracic echocardiogram performed pre- and post-Impella. ResultsOf 24 patients, 33% had moderate-to-severe/severe FMR, 38% had mild-moderate/moderate FMR, and 29% had trace/mild FMR on pre-Impella transthoracic echocardiogram. Additional right ventricular assist device was simultaneously inserted in 3 patients, of whom 1 had severe, 1 had moderate, and another had mild FMR pre-Impella. Despite maximally tolerated Impella unloading, 6 patients (25%) had persistent moderate-severe/severe FMR, and 9 (37.5%) patients had persistent moderate FMR. Overall, however, there was a decrease in central venous pressure, pulmonary artery diastolic pressure, serum lactate, and vasoactive-inotrope score at 24 ​hours post-Impella, and survival was high at 83%. ConclusionsIn a retrospective cohort of patients admitted with HF-CS who underwent Impella 5.5 implant for hemodynamic support, Impella did not seem to acutely ameliorate FMR severity. Despite this, there was a significant improvement in hemodynamic response at 24 ​hours post-Impella. In carefully selected patients, especially those with isolated left ventricular failure, Impella 5.5 may provide adequate hemodynamic support even in the presence of higher severity FMR.

Transcatheter Mitral Valve Repair in Patients With Atrial Functional Mitral Regurgitation

BackgroundAmong patients with severe functional mitral regurgitation (FMR), atrial functional mitral regurgitation (aFMR) represents an underrecognized entity. Data regarding outcomes after mitral valve transcatheter edge-to-edge repair (M-TEER) in aFMR remain scarce. ObjectivesThe objective of this study was to analyze the outcome of aFMR patients undergoing M-TEER. MethodsUsing patients from the international EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) registry undergoing M-TEER for FMR, the authors analyzed baseline characteristics and 2-year outcomes in aFMR in comparison to non-aFMR and ventricular FMR. Additionally, the impact of right ventricular dysfunction (RVD) (defined as right ventricular to pulmonary artery uncoupling) on outcome after M-TEER was assessed. ResultsAmong 1,608 FMR patients treated by M-TEER, 126 (7.8%) were categorized as aFMR. All 126 aFMR patients had preserved left ventricular function without regional wall motion abnormalities, left arterial dilatation and Carpentier leaflet motion type I. Procedural success (defined as mitral regurgitation ≤2+ at discharge) was 87.2% (P < 0.001) and New York Heart Association (NYHA) functional class significantly improved during follow-up (NYHA functional class III/IV: 86.5% at baseline to 36.6% at follow-up; P < 0.001). The estimated 2-year survival rate in aFMR patients was 70.4%. Two-year survival did not differ significantly between aFMR, non-aFMR, and ventricular FMR. Besides NYHA functional class IV, RVD was identified as a strong independent predictor for 2-year survival (HR: 2.82 [95% CI: 1.24-6.45]; P = 0.014). ConclusionsaFMR is a frequent cause of FMR and can be effectively treated with M-TEER to improve symptoms at follow-up. Advanced heart failure symptoms and RVD were identified as important risk factors for survival in aFMR patients.

Myocardial Contractile Mechanics in Ischemic Mitral Regurgitation: Multicenter Data Using Stress Perfusion Cardiovascular Magnetic Resonance

BackgroundLeft ventricular (LV) ischemia has been variably associated with functional mitral regurgitation (FMR). Determinants of FMR in patients with ischemia are poorly understood. ObjectivesThis study sought to test whether contractile mechanics in ischemic myocardium underlying the mitral valve have an impact on likelihood of FMR. MethodsVasodilator stress perfusion cardiac magnetic resonance was performed in patients with coronary artery disease (CAD) at multiple centers. FMR severity was confirmed quantitatively via core lab analysis. To test relationship of contractile mechanics with ischemic FMR, regional wall motion and strain were assessed in patients with inducible ischemia and minimal (≤5% LV myocardium, nontransmural) infarction. ResultsA total of 2,647 patients with CAD were studied; 34% had FMR (7% moderate or greater). FMR severity increased with presence (P < 0.001) and extent (P = 0.01) of subpapillary ischemia: patients with moderate or greater FMR had more subpapillary ischemia (odds ratio [OR]: 1.13 per 10% LV; 95% CI: 1.05-1.21; P = 0.001) independent of ischemia in remote regions (P = NS); moderate or greater FMR prevalence increased stepwise with extent of ischemia and infarction in subpapillary myocardium (P < 0.001); stronger associations between FMR and infarction paralleled greater wall motion scores in infarct-affected territories. Among patients with inducible ischemia and minimal infarction (n = 532), wall motion and radial strain analysis showed impaired subpapillary contractile mechanics to associate with moderate or greater FMR (P < 0.05) independent of remote regions (P = NS). Conversely, subpapillary ischemia without contractile dysfunction did not augment FMR likelihood. Mitral and interpapillary dimensions increased with subpapillary radial strain impairment; each remodeling parameter associated with impaired subpapillary strain (P < 0.05) independent of remote strain (P = NS). Subpapillary radial strain (OR: 1.13 per 5% [95% CI: 1.02-1.25]; P = 0.02) and mitral tenting area (OR: 1.05 per 10 mm2 [95% CI: 1.00-1.10]; P = 0.04) were associated with moderate or greater FMR controlling for global remodeling represented by LV end-systolic volume (P = NS): when substituting sphericity for LV volume, moderate or greater FMR remained independently associated with subpapillary radial strain impairment (OR: 1.22 per 5% [95% CI: 1.02-1.47]; P = 0.03). ConclusionsAmong patients with CAD and ischemia, FMR severity and adverse mitral apparatus remodeling increase in proportion to contractile dysfunction underlying the mitral valve.

Response of functional mitral regurgitation in nonischemic cardiomyopathy to left bundle branch pacing.

Functional mitral regurgitation (FMR) in patients with cardiomyopathy is correlated with morbidity and mortality in heart failure. The response of FMR to cardiac resynchronization therapy (CRT) varies. The purpose of this study was to analyze the incidence and severity of FMR in patients with nonischemic cardiomyopathy (NICM) and left bundle branch block (LBBB) and the response to left bundle branch pacing (LBBP). Patients who had undergone LBBP for NICM, LBBB, and FMR between 2019 to 2021 were included retrospectively in the study. A total of 79 patients were identified, of whom 6 were excluded (5 no consistent LBB capture, 1 prosthetic mitral valve). The remaining 73 patients were divided into 2 groups based on the severity of FMR into group I with mild FMR (n = 35 [48%]) and group II with significant FMR (n = 38 [52%]). Mean follow-up duration was comparable in both groups. Group II was characterized by higher N-terminal pro-brain natriuretic peptide levels, New York Heart Association functional class, and larger left ventricular dimensions. LBBP resulted in significant reduction in QRS duration in both group I (113.8 ± 12.7 ms; P <.0001) and group II (117.3± 10.3 m s; P <.0001). LBBP resulted in similar percentage reduction in QRS duration (-31% ± 10% vs -33% ± 8%; P = .34), left ventricular (LV) end-diastolic diameter (-8% ± 10% vs -11% ± 12%; P = .25), LV end-diastolic volume (-26%± 12% vs -31% ± 27%; P = .31), and LV end-systolic volume (-39% ± 16% vs -37% ± 30%; P = .72) in groups I and II, respectively. Percentage change (+59% ± 39% vs +59% ± 41%; P = 1) and absolute change (+19.9% ± 10.4% vs +17% ± 10.04%; P = .22) in LV ejection fraction were similar in both groups. In group II, 31 patients (82%) showed significant reduction in FMR severity during follow-up. No patients in group I showed worsening of FMR. LBBP resulted in excellent electrical resynchronization with significant reduction in FMR severity in the majority of patients with significant FMR and no worsening of FMR from baseline in any patient.