Functional Mitral Regurgitation Research Articles

A case of mitral regurgitation due to bilateral undifferentiated papillary muscles with detailed preoperative diagnosis of associated morphological abnormalities

Incomplete differentiation of the mitral valve structures during fetal life results in the papillary muscles and tendon cords becoming hypoplastic, a condition termed undifferentiated papillary muscles (UDPM). This fetal abnormality causes a group of diseases that cause mitral valve dysfunction in adult life. Here, we report a case of UDPM centered on the medial posterior apex in which detailed morphological abnormalities were diagnosed preoperatively using echocardiography and three-dimensional computed tomography (3DCT) analysis, contributing to plastic surgery.The patient was a 64-year-old man who was followed up for several years for atrial functional mitral regurgitation (MR), ultimately developing heart failure. His MR was severe, and he was referred for surgery.Echocardiography revealed restrictive tendon cords primarily in the posterior apex, abnormal muscle bundles in the lower part of the valve, and findings indicative of UDPM; this was considered the main cause of MR. The patient had surgery findings similar to the preoperative diagnosis, which greatly aided the surgery. Postoperatively, the MR was well-controlled and mild.UDPM may present as various morphologic and functional abnormalities, including partial club-shaped tendinous MR and rheumatoid mitral stenosis, which are rarely accurately diagnosed preoperatively. Detailed analysis of morphological abnormalities using 3DCT or other methods may be beneficial for a successful plasty.

Ertugliflozin for Functional Mitral Regurgitation Associated With Heart Failure: EFFORT Trial.

The morbidity and mortality rates of patients with heart failure (HF) and functional mitral regurgitation (MR) remain substantial despite guideline-directed medical therapy for HF. We evaluated the efficacy of ertugliflozin for reduction of functional MR associated with HF with mild to moderately reduced ejection fraction. The EFFORT trial (Ertugliflozin for Functional Mitral Regurgitation) was a multicenter, double-blind, randomized trial to examine the hypothesis that the sodium-glucose cotransporter 2 inhibitor ertugliflozin is effective for improving MR in patients with HF with New York Heart Association functional class II or III, 35%≤ejection fraction<50%, and effective regurgitant orifice area of chronic functional MR >0.1 cm2 on baseline echocardiography. We randomly assigned 128 patients to receive either ertugliflozin or placebo in addition to guideline-directed medical therapy for HF. The primary end point was change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, left ventricular (LV) volume indices, left atrial volume index, LV global longitudinal strain, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). The treatment groups were generally well-balanced with regard to baseline characteristics: mean age, 66±11 years; 61% men; 13% diabetes; 51% atrial fibrillation; 43% use of angiotensin receptor-neprilysin inhibitor; ejection fraction, 42±8%; and effective regurgitant orifice area, 0.20±0.12 cm2. The decrease in effective regurgitant orifice area was significantly greater in the ertugliflozin group than in the placebo group (-0.05±0.06 versus 0.03±0.12 cm2; P<0.001). Compared with placebo, ertugliflozin significantly reduced regurgitant volume by 11.2 mL (95% CI, -16.1 to -6.3; P=0.009), left atrial volume index by 6.0 mL/m2 (95% CI, -12.16 to 0.15; P=0.005), and LV global longitudinal strain by 1.44% (95% CI, -2.42% to -0.46%; P=0.004). There were no significant between-group differences regarding changes in LV volume indices, ejection fraction, or NT-proBNP levels. Serious adverse events occurred in one patient (1.6%) in the ertugliflozin group and 6 (9.2%) in the placebo group (P=0.12). Among patients with functional MR associated with HF, ertugliflozin significantly improved LV global longitudinal strain and left atrial remodeling, and reduced functional MR. Sodium-glucose cotransporter 2 inhibitors may be considered for patients with functional MR. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04231331.

Randomized investigation of the MitraClip device in heart failure: Design and rationale of the RESHAPE-HF2 trial design.

The safety and effectiveness of the MitraClip device to treat functional mitral regurgitation (FMR) has been tested in previous clinical trials yielding somewhat heterogeneous results in heart failure (HF) patients. Over time, the MitraClip device system has been modified and clinical practice evolved to consider also less severely diseased HF patients with FMR for this therapeutic option. The RESHAPE-HF2 trial aims to assess the safety and effectiveness of the MitraClip device system on top of medical therapy considered optimal in the treatment of clinically significant FMR in symptomatic patients with chronic HF. The RESHAPE-HF2 is an investigator-initiated, prospective, randomized, parallel-controlled, multicentre trial designed to evaluate the use of the MitraClip device (used in the most up-to-date version as available at sites) plus optimal standard of care therapy (device group) compared to optimal standard of care therapy alone (control group). Eligible subjects have signs and symptoms of HF (New York Heart Association [NYHA] class II-IV despite optimal therapy), and have moderate-to-severe or severe FMR, as confirmed by a central echocardiography core laboratory; have an ejection fraction between ≥20% and ≤50% (initially 15-35% for NYHA class II patients, and 15-45% for NYHA class III/IV patients); have been adequately treated per applicable standards, and have received appropriate revascularization and cardiac resynchronization therapy, if eligible; had a HF hospitalization or elevated natriuretic peptides (B-type natriuretic peptide [BNP] ≥300 pg/ml or N-terminal proBNP ≥1000 pg/ml) in the last 90 days; and in whom isolated mitral valve surgery is not a recommended treatment option. The trial has three primary endpoints, which are these: (i) the composite rate of total (first and recurrent) HF hospitalizations and cardiovascular death during 24 months of follow-up, (ii) the rate of total (i.e. first and recurrent) HF hospitalizations within 24 months, and (iii) the change from baseline to 12 months in the Kansas City Cardiomyopathy Questionnaire overall score. The three primary endpoints will be analysed using the Hochberg procedure to control the familywise type I error rate across the three hypotheses. The RESHAPE-HF2 trial will provide sound evidence on the MitraClip device and its effects in HF patients with FMR. The recruitment was recently completed with 506 randomized patients.

Paradox of disproportionate atrial functional mitral regurgitation and survival after transcatheter edge-to-edge repair.

This study aims to assess the applicability of the mitral regurgitation (MR) proportionality concept in patients with atrial functional mitral regurgitation (aFMR) treated with transcatheter edge-to-edge repair (M-TEER). We hypothesized that patients with disproportionate MR (higher MR relative to left ventricular size) would exhibit different outcomes compared to those with proportionate MR, despite undergoing M-TEER. We retrospectively analysed 98 patients with aFMR from the EuroSMR registry who underwent M-TEER between 2008 and 2019. Patients met criteria for aFMR (normal indexed left ventricular end-diastolic volume [LVEDV], preserved left ventricular ejection fraction [LVEF]≥50% without regional wall motion abnormalities, and structurally normal mitral valves). We excluded patients with missing effective regurgitant orifice area (EROA) or LVEDV data. The primary endpoint was 2-year mortality, with an EROA/LVEDV ratio employed to differentiate disproportionate from proportionate MR. Procedural success and baseline characteristics were analysed, and multivariate Cox proportional hazards models were used to identify mortality predictors. The mean patient age was 79±7.3years, with 68.8% female, and 79% had a history of atrial fibrillation. The mean EROA was 0.27±0.14cm2, and LVEDV was 95.6±33.7mL. Disproportionate MR was identified with an EROA/LVEDV ratio >0.339cm2/100mL. While procedural success was similar in both groups, disproportionate MR was associated with a numerically higher estimate of systolic pulmonary artery pressures (sPAP) and rates of NYHA ≥III and TR≥3+. Disproportionate MR had a significant association with increased 2-year mortality (P<0.001). The EROA/LVEDV ratio and tricuspid annular plane systolic excursion (TAPSE) were independent predictors of 2-year mortality (EROA/LVEDV: HR: 1.35, P=0.010; TAPSE: HR: 0.85, P=0.020). This analysis introduces the MR proportionality concept in aFMR patients and its potential prognostic value. Paradoxically, disproportionate MR in aFMR was linked to a 1.35-fold increase in 2-year mortality post-M-TEER, emphasizing the importance of accurate preprocedural FMR characterization. Our findings in patients with disproportionate MR indicate that a high degree of aFMR with high regurgitant volumes may lead to aggravated symptoms, which is a known contributor to increased mortality following M-TEER. These results underline the need for further research into the pathophysiology of aFMR to inform potential preventative and therapeutic strategies, ensuring optimal patient outcomes.

Unusual origins of cardiac insufficiency: a case of iliac arteriovenous fistula post-spinal disc surgery

In this case report, we present the unique and intriguing case of a 57-year-old man who experienced exertional palpitations and shortness of breath for 5 years. He was diagnosed with idiopathic heart failure three years ago, leading to diuretic treatment. Physical examination revealed notable left lower extremity swelling, severe varicose veins, and cardiac murmurs. Echocardiography showed significant cardiac enlargement and severe functional mitral and tricuspid valve regurgitation. Computed tomography (CT) imaging uncovered a 10 mm left common iliac arteriovenous fistula, causing abnormal early filling of the inferior vena cava (IVC) and marked IVC dilation. Open surgical repair of the arteriovenous fistula resulted in symptom relief and improved cardiac function. This case underscores the importance of considering unusual causes in heart failure patients and highlights the value of early diagnosis and intervention in complex cardiac-vascular interactions.

Assessing emerging causes of mitral regurgitation: atrial functional mitral regurgitation.

Functional or secondary mitral regurgitation is linked to increased cardiovascular morbidity and mortality. From a mechanical perspective, secondary mitral regurgitation occurs due to an imbalance between the forces that tether the mitral leaflets and those that close them. This results in incomplete coaptation. Most commonly, functional mitral regurgitation, which occurs in both ischaemic and non-ischaemic disease states, is usually caused by dysfunction and changes in the left ventricle. Atrial functional mitral regurgitation (AFMR) is a disease state that has been more recently recognized. It occurs when mitral annular enlargement is associated with left atrial dilatation, preserving left ventricular geometry and function. AFMR is typically seen in patients with chronic atrial fibrillation or heart failure who have a conserved ejection fraction. Published reports and ongoing investigations vary in how they define AFMR. This publication examines the pathophysiology of AFMR and highlights the importance of having a common working standard for the definition of AFMR to ensure consistency in the data reported and to drive forward the much needed research into the outcomes and treatment strategies in this area. Several studies have reported that restrictive annuloplasty and transcatheter edge-to-edge repair can reduce mitral regurgitation and improve symptoms. This narrative review will explore the pathophysiology, echocardiographic diagnosis and treatment of AFMR.

Prognostic Value of Left Ventricular Global Longitudinal Strain in Transcatheter Edge-to-Edge Repair for Chronic Primary Mitral Regurgitation.

Left ventricular global longitudinal strain (LVGLS) is a known outcome predictor in transcatheter edge-to-edge repair (TEER) for functional mitral regurgitation (MR). We aimed to assess its prognostic yield in the setting of TEER for chronic primary MR. We conducted a single-center, retrospective analysis of 323 consecutive patients undergoing isolated, first-time procedures. Stratified by baseline LVGLS quartiles (≤-19%, -18.9-(-16)%, -15.9-(-12)%,  > -12%), the cohort was evaluated for the primary composite outcome of all-cause mortality or heart failure hospitalizations, as well as secondary endpoints consisting of mitral reinterventions and the persistence of significant residual MR and/or functional disability - all along the first year after intervention. Subjects with worse (i.e., less negative) LVGLS exhibited higher comorbidity, more advanced HF, and elevated procedural risk. Post-TEER, those belonging to the worst LVGLS quartile group sustained increased mortality (16.9 vs 6.3%, Log-Rank p = 0.005, HR 1.75, 95% CI 1.08-4.74, p = 0.041) and, when affected by LV dysfunction/dilatation, more primary outcome events (21.1 vs 11.5%, Log-Rank p = 0.037, HR 1.68, 95% CI 1.02-5.46, p = 0.047). No association was demonstrated with other endpoints. Upon exploratory analysis, 1-month postprocedural LVGLS directly correlated with and was worse than its baseline counterpart by 1.6%, and a more impaired 1-month value - but not the presence/extent of deterioration - conferred heightened risk for the primary outcome. TEER for chronic primary MR is feasible, safe, and efficacious irrespective of baseline LVGLS. Yet, worse baseline LVGLS forecasts a less favorable postprocedural course, presumably reflecting a higher-risk patient profile.

Two-Year Clinical Outcome of MitraClip Transcatheter Edge-to-Edge Repair From the J-MITRA Registry Data.

The introduction of transcatheter edge-to-edge repair for moderate-to-severe or severe mitral regurgitation (MR) utilizing the MitraClip system became reimbursed and clinically accessible in Japan in April 2018. This study presents the 2-year clinical outcomes of all consecutively treated patients who underwent MitraClip implantation in Japan and were prospectively enrolled in the Japanese Circulation Society-oriented J-MITRA registry.Methods and Results: Analysis encompassed 2,739 consecutive patients enrolled in the J-MITRA registry with informed consent (mean age: 78.3±9.6 years, 1,550 males, STS risk score 11.7±8.9), comprising 1,999 cases of functional MR, 644 of degenerative MR and 96 in a mixed group (DMR and FMR). The acute procedure success rate was 88.9%. After MitraClip implantation, >80% exhibited an MR grade ≤2+ and the trend was sustained over the 2 years. Within this observation period, the mortality rate was 19.3% and the rate of heart failure readmissions was 20.6%. The primary composite endpoint, inclusive of cardiovascular death and heart failure readmission, was significantly higher in patients with functional MR than in with degenerative MR (32.0% vs. 17.5%, P<0.001). The 2-year clinical outcomes after MitraClip implantation were deduced from comprehensive data within an all-Japan registry.

Efficacy of Native T1 Mapping for Patients With Non-Ischemic Cardiomyopathy and Ventricular Functional Mitral Regurgitation Undergoing Transcatheter Edge-to-Edge Repair.

We investigated the efficacy of left ventricular (LV) myocardial damage by native T1mapping obtained with cardiac magnetic resonance (CMR) for patients undergoing transcatheter edge-to-edge repair (TEER).Methods and Results: We studied 40 symptomatic non-ischemic heart failure (HF) patients and ventricular functional mitral regurgitation (VFMR) undergoing TEER. LV myocardial damage was defined as the native T1Z-score, which was converted from native T1values obtained with CMR. The primary endpoint was defined as HF rehospitalization or cardiovascular death over 12 months after TEER. Multivariable Cox proportional hazards analysis showed that the native T1Z-score was the only independent parameter associated with cardiovascular events (hazard ratio 3.40; 95% confidential interval 1.51-7.67), and that patients with native T1Z-scores <2.41 experienced significantly fewer cardiovascular events than those with native T1Z-scores ≥2.41 (P=0.001). Moreover, the combination of a native T1Z-score <2.41 and more severe VFMR (effective regurgitant orifice area [EROA] ≥0.30 cm2) was associated with fewer cardiovascular events than a native T1Z-score ≥2.41 and less severe VFMR (EROA <0.30 cm2; P=0.002). Assessment of baseline LV myocardial damage based on native T1Z-scores obtained with CMR without gadolinium-based contrast media is a valuable additional parameter for better management of HF patients and VFMR following TEER.

Preprocedural Evaluation of Ventricular Functional Mitral Regurgitation Upon Transcatheter Edge-to-Edge Repair by Noninvasive Imaging　- An Emerging Clinical Standard.

Preprocedural Evaluation of Ventricular Functional Mitral Regurgitation Upon Transcatheter Edge-to-Edge Repair by Noninvasive Imaging　- An Emerging Clinical Standard.

Long-term cost-effectiveness of transcatheter mitral valve repair in HF patients with secondary mitral regurgitation.

The long-term cost-effectiveness of MitraClip in heart failure patients with secondary mitral regurgitation is still unclear. This study aimed to evaluate the long-term cost-effectiveness of MitraClip added to guideline-directed medical therapy vs. guideline-directed medical therapy alone in heart failure patients with secondary mitral regurgitation from the perspective of the healthcare systems of mainland China, the United Kingdom, Germany, and the United States. A two-stage (decision+Markov) model was built. Health utilities were defined by the New York Heart Association class, heart failure re-hospitalization, and death and were calculated based on the 5year follow-up results of the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation trial. Direct healthcare costs were derived from the nationally representative data. Future utilities and costs were discounted at country-specific rates. The primary outcome was the lifetime incremental cost-effectiveness ratio. The mean age of the base case in our model was 72.2years. Over a lifetime horizon, treatment with MitraClip was associated with 829 fewer heart failure re-hospitalizations per 1000 treated patients. The MitraClip treatment was associated with incremental quality-adjusted life-year gains of 0.71, 0.76, 0.78, and 0.78, as well as incremental cost-effectiveness ratios of ¥468462, £28910, €26045, and $71199 per quality-adjusted life-year for a lifetime horizon in mainland China, the United Kingdom, Germany, and the United States, respectively. In probabilistic sensitivity analysis, 0.2%, 59.4%, 99.6%, and 84.7% of patients were cost-effective in mainland China, the United Kingdom, Germany, and the United States at the country-specific willingness-to-pay thresholds. MitraClip+guideline-directed medical therapy was cost-effective in heart failure patients with secondary mitral regurgitation in the United Kingdom, Germany, and the United States, but not in mainland China from the perspective of the national healthcare system.

Sequential composite BIMA grafting for 3v-CAD: factors that predict successful outcome of the one-inflow and two-inflow revascularization techniques.

The effect of one-inflow and two-inflow coronary surgical revascularization techniques inclosing skeletonized double mammary artery (BIMA) as T-graft on outcome is studied. Early ad mid-term outcome of complete BIMA revascularization (C-T-BIMA) versus left-sided BIMA with right-sided aorto-coronary bypass (L-T-BIMA + R-CABG) is quantified and analyzed by multivariate logistic regression, Cox-regression, and Kaplan-Meier analysis in a series of 204 consecutive patients treated for triple-vessel coronary disease (3v-CAD). The L-T-BIMA + R-CABG technique (n = 104) enables higher number of total (4.02 ± 0.87 vs. 3.71 ± 0.69, p = 0.015) and right-sided (1.21 ± 0.43 vs. 1.02 ± 0.32, p = 0.001) coronary anastomoses, improves total bypass flow (125.88 ± 92.41 vs. 82.50 ± 49.26ml, p < 0.0001) and bypass flow/anastomosis (31.83 ± 23.9 vs.22.77 ± 14.23, p = 0.001), and enhances completeness of revascularization (84% vs.69%, p = 0.014) compared to C-T-BIMA strategy (n = 100), respectively. Although the incidence of MACCE was comparable in the two groups (8% vs.1.2%, p = 0.055), the progression of functional mitral regurgitation (FMR) was significantly lower after L-T-BIMA + R-CABG, then after C-T-BIMA (47% vs.64%, p = 0.017). The use of C-T-BIMA-technique (HR = 4.2, p = 0.01) and preoperative RCA occlusion (HR = 3.006, p = 0.023) predicted FMR progression, whereas L-T-Graft + R-CABG technique protected against it (X2 = 14.04, p < 0.0001) independent of the anatomic and clinical complexity (Syntax score I: HR = 16.2, p = 0.156, Syntax score II: HR = 1.901, p = 0.751), of early- (0.96% vs.2%, p = 0.617) and mid-term mortality (5.8% vs.4%, p = 0.748) when compared to C-T-BIMA, respectively. The two-inflow coronary revascularization by L-T-BIMA + R-CABG better protects against FMR progression without increasing MACCE and mortality. Older patients with RCA occlusion and reduced LV-EF benefit most from the two-inflow L-T-BIMA + R-CABG technique. Younger 3v-CAD patients with normal LV-EF can preferentially be managed with the one-inflow C-T-BIMA; however, long-term outcome remains to be revealed.

Prevalence and clinical outcomes of isolated or combined moderate to severe mitral and tricuspid regurgitation in patients with cardiac amyloidosis.

Evidence on the epidemiology and prognostic significance of mitral regurgitation (MR) and tricuspid regurgitation (TR) in patients with cardiac amyloidosis (CA) is scarce. Overall, 538 patients with either transthyretin (ATTR, n = 359) or immunoglobulin light-chain (AL, n = 179) CA were included at three Italian referral centres. Patients were stratified according to isolated or combined moderate/severe MR and TR. Overall, 240 patients (44.6%) had no significant MR/TR, 112 (20.8%) isolated MR, 66 (12.3%) isolated TR, and 120 (22.3%) combined MR/TR. The most common aetiologies were atrial functional MR, followed by primary infiltrative MR, and secondary TR due to right ventricular (RV) overload followed by atrial functional TR. Patients with isolated or combined MR/TR had a more frequent history of heart failure (HF) hospitalization and atrial fibrillation, worse symptoms, and higher levels of NT-proBNP as compared to those without MR/TR. They also presented more severe atrial enlargement, atrial peak longitudinal strain impairment, left ventricular (LV) and RV systolic dysfunction, and higher pulmonary artery systolic pressures. TR carried the most advanced features. After adjustment for age, sex, CA subtypes, laboratory, and echocardiographic markers of CA severity, isolated TR and combined MR/TR were independently associated with an increased risk of all-cause death or worsening HF events, compared to no significant MR/TR [adjusted HR 2.75 (1.78-4.24) and 2.31 (1.44-3.70), respectively]. In a large cohort of patients with CA, MR, and TR were common. Isolated TR and combined MR/TR were associated with worse prognosis regardless of CA aetiology, LV, and RV function, with TR carrying the highest risk.

Functional tricuspid regurgitation and efficacy of electrical cardioversion in patients with atrial fibrillation and atrial functional mitral regurgitation.

Atrial functional mitral regurgitation (afMR) is common in patients with atrial fibrillation (AF). The presence of functional tricuspid regurgitation (fTR), which arises as a secondary effect of afMR, has the potential to impact the effectiveness of procedures aimed at restoring normal heart rhythm. In this study, we sought to evaluate the efficacy of electrical cardioversion (CVE) in AF regarding the presence and degree of fTR in patients with afMR. Retrospective analysis included 521 patients with persistent AF on optimal medical therapy undergoing CVE. 157 (30.1%) patients had afMR (characterized by left ventricle ejection fraction ≥ 50% and LA dilatation) and were divided into 2 groups: the group with fTR (107, 68.2%) and the group without fTR (50, 31.9%). Patients with afMR and fTR had a higher prevalence of metabolic syndrome (p = 0.02) and greater right atrial area (p < 0.01) compared to patients without fTR. The efficacy of CVE was lower in the group with fTR in comparison to patients with isolated afMR (82.2% vs. 94%; p = 0.048) and it was unrelated to the degree of fTR (p = 0.15) and RVSP (p = 0.56). The energy required for successful CVE was comparable regardless of the presence (p = 0.26) or severity of fTR (p = 0.94). The fTR frequently coexists with afMR and it significantly diminishes the effectiveness of CVE for treating AF. The degree of fTR does not appear to influence the efficacy of CVE.

Mitral Regurgitation “Proportionality” in Functional Mitral Regurgitation and Outcomes After Mitral Valve Transcatheter Edge-to-Edge Repair: A Systematic Review and Meta-Analysis

BackgroundCertain patients with functional mitral regurgitation survive longer with fewer heart failure hospitalizations after undergoing transcatheter edge-to-edge repair (TEER); however, clinical markers identifying who will benefit have not been established. The ‘proportionality’ of mitral regurgitation (MR) severity compared to left ventricular size has been hypothesized to predict clinical outcome. MethodsWe sought to combine existing studies to compare outcomes between ‘proportionate’ MR and ‘disproportionate’ MR in patients undergoing TEER. PubMed and Medline were searched from January 2018 until May 2023. Data was extracted and synthesized by 2 independent authors using random effects models with risk ratios (RRs) for binary outcomes. The primary outcome was a combined endpoint of all-cause mortality or heart failure hospitalization (ACM/HFH). Other outcomes of interest included ACM and residual >2+ MR after TEER. ResultsSix trials with a total of 1594 patients (mean age 71 years, 66% male) were included, which assessed MR proportionality using either a ratio of estimated regurgitant orifice area to left ventricular end-diastolic volume (EROA:LVEDV) or regurgitant fraction. Seven hundred and five (mean age 70 years, 75% male) were classified as proportionate MR, and 889 (mean age 72 years, 60% male) had disproportionate MR. There was no significant association between MR proportionality (by EROA:LVEDV) and ACM (RR 0.79, 95% confidence interval [CI] 0.44-1.42). Proportionality did not significantly associate with ACM/HFH, though there were divergent effect signals when proportionality was measured by EROA:LVEDV (RR 0.80, 95% CI 0.45-1.44) or regurgitant fraction (RR 1.48, 95% CI 0.53-4.11). Disproportionate MR showed a greater association with residual MR > 2+ post-TEER that did not meet statistical significance (RR 1.86, 95% CI 0.77-4.49). ConclusionsIn patients undergoing TEER for functional mitral regurgitation, MR proportionality was not significantly associated with ACM/HFH, all-cause mortality, or residual MR.

The Natural History of Atrial Functional Mitral Regurgitation

BackgroundThe natural history of moderate/severe atrial functional mitral regurgitation (AFMR) is unknown. ObjectivesThe authors sought to study the incidence of left ventricular (LV) systolic dysfunction (LVSD), progression or regression of ≥mild-moderate AFMR, and impact on mortality. MethodsAdults with left atrial (LA) volume index ≥40 mL/m2, ≥mild-moderate AFMR, and follow-up echocardiogram were followed for incident LVSD (ejection fraction <50% and ≥10% lower than baseline), progression of mild-moderate/moderate AFMR to severe, and persistent regression of AFMR to no/trivial. Relation of AFMR progression or regression as time-dependent covariates with all-cause mortality was studied. Incidence of LVSD was compared with patients with no/mild AFMR matched on age, sex, comorbidities and ejection fraction. Patients were followed until mitral intervention, myocardial infarction, or last follow-up. ResultsA total of 635 patients (median age 75 years, 51% female, 96% mild-moderate/moderate AFMR, 4% severe AFMR) were included. Over a median 2.2 years (Q1-Q3: 1.0-4.3 years), incidence rates per 100 person-years were 3.2 for LVSD (P = 0.52 vs patients with no/mild AFMR), 1.9 for progression of AFMR, and 3.9 for regression. Female sex and larger LA volume index were independently associated with progression, whereas younger age, male sex, absent atrial fibrillation, and higher LA emptying fraction were independently associated with regression. Neither AFMR progression nor regression was independently associated with mortality. Instead, independent risk factors for mortality included older age, concentric LV geometry, and higher estimated LV filling and pulmonary pressures. ConclusionsIn patients with predominantly mild-moderate/moderate AFMR, regression of MR was more common than progression, but neither was associated with mortality. Instead, diastolic function abnormalities were more important. Over a median 2-year follow-up, LVSD risk was not increased.

Advancements in MitraClip Intervention for Mitral Regurgitation: A Comprehensive Review and Comparative Analysis of Clinical Trials.

This comprehensive review explores the evolution and clinical impact of MitraClip intervention in the management of mitral regurgitation. Mitral regurgitation results from dysfunction in the mitral valve (MV) apparatus. The MitraClip Clip Delivery System was approved by the Food and Drug Administration (FDA) in 2013. The discussion delves into the procedural foundation of MitraClip intervention, primarily based on Alfieri's technique of edge-to-edge leaflet approximation. As highlighted by key clinical trials, includingEndovascular Valve Edge-to-Edge Repair(EVEREST) II Trial, Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) Trial, and Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation (MITRA-FR) trial, the efficacy and safety of MitraClip were evaluated in comparison to surgical interventions and guideline-directed medical therapy. Notably, the COAPT demonstrated significant benefits in reducing all-cause mortality and heart failure hospitalization, while the MITRA-FR presented contrasting results, emphasizing the importance of patient selection. An analysis of the EVEREST II trial underscores MitraClip's potential to achieve comparable outcomes to surgical intervention, emphasizing its role in reducing mitral regurgitation and improving clinical status. However, limitations and complications, such as device-related issues and the potential impact on future MV surgery, are discussed. The study also explores the evolving landscape of MV interventions, reflecting advancements and the growing acceptance of MitraClip. In conclusion, the MitraClip device represents a significant advancement in the treatment of mitral regurgitation. The data presented highlights its promising results in terms of reduced hospitalization rates, improved in-hospital mortality, and enhanced quality of life for patients. However, challenges remain, and careful consideration of patient selection and underlying pathology is crucial in determining the optimal treatment approach. Ongoing research and clinical experience will continue to refine our understanding of MitraClip's role in the evolving landscape of MV interventions.

Outcomes of transcatheter edge-to-edge repair for atrial functional mitral regurgitation.

The prognostic benefits of transcatheter edge-to-edge repair (TEER) remain unclear in patients with atrial functional mitral regurgitation (AFMR). We aimed to investigate the clinical outcomes of TEER for patients with AFMR. We retrospectively classified functional mitral regurgitation (FMR) patients undergoing TEER into those with AFMR or ventricular FMR (VFMR). A residual MR ≤1+ at discharge was considered optimal mitral regurgitation (MR) reduction, and an elevated mean mitral valve pressure gradient (MPG) was defined as an MPG ≥5 mmHg at discharge. The primary outcome was a composite of all-cause mortality and hospitalisation due to heart failure within one year. Of 441 FMR patients, 125 patients were considered as having AFMR. Residual MR ≤1+ was associated with a lower risk of the composite outcome in both AFMR and VFMR patients, while an MPG ≥5 mmHg was associated with a higher risk of the composite outcome in patients with AFMR but not with VFMR. AFMR patients with residual MR ≤1+ and an MPG ≥5 mmHg, as well as those with residual MR >1+, had a higher incidence of the composite outcome than those with residual MR ≤1+ and an MPG <5 mmHg (50.7%, 41.8%, and 14.3%, respectively; p<0.001). This association was consistent after adjustment for clinical and echocardiographic characteristics. An MR reduction to ≤1+ following TEER was associated with a lower risk of clinical outcomes in patients with AFMR, while an MPG ≥5 mmHg was related to a higher risk of clinical outcomes. Optimal MR reduction by TEER may have potential benefits on the prognosis of patients with AFMR, although the prognostic benefit may be attenuated by an elevated MPG.

An Updated Meta-Analysis of Treatment in Patients with Heart Failure Complicated Ventricular Functional Mitral Regurgitation

An Updated Meta-Analysis of Treatment in Patients with Heart Failure Complicated Ventricular Functional Mitral Regurgitation

The effect of a smaller spacer in the PASCAL Ace on residual mitral valve orifice area.

Mitral transcatheter edge-to-edge repair (M-TEER) is an established treatment for functional mitral regurgitation (FMR) associated with a risk of creating iatrogenic stenosis. To investigate the impact of the P10 and its larger spacer compared to the narrower Ace and its smaller spacer on reduction of mitral valve orifice area (MVOA) during M-TEER. Consecutive patients undergoing M-TEER for treatment of severe FMR were screened retrospectively. Patients with a single PASCAL device implantation within the central segments of the MV leaflets, non-complex anatomy, and baseline MVOA ≥ 3.5cm2 were selected. Intraprocedural transesophageal echocardiography was used to compare MVOA reduction with 3D multiplanar reconstruction and direct planimetry. Device selection did not follow a prespecified MVOA threshold. Seventy-two patients (81.0 years, IQR {74.3-85.0}) were included. In 32 patients, the P10 was implanted (44.4%). MR severity (p = 0.66), MR reduction (p = 0.73), and body surface area (p = 0.56) were comparable. Baseline MVOA tended to be smaller in P10 patients with the larger spacer (5.0 ± 1.1 vs. 5.4 ± 1.3cm2, p = 0.18), however, residual MVOA was larger in these patients (2.7 ± 0.7 vs. 2.3 ± 0.6cm2, p = 0.03). Accordingly, relative MVOA reduction was significantly less in P10 patients (- 45.9 ± 7.6 vs. - 56.3 ± 7.0%, p < 0.01). Indirect annuloplasty was more pronounced in Ace patients whereas mean transmitral gradients were similar. In FMR patients with non-complex anatomy, the larger spacer of the P10 maintains greater MVOA with similar MR reduction. Hence, the use of the PASCAL Ace device in patients with small MVOAs might correlate with a risk of both clinically relevant orifice reduction and even iatrogenic stenosis.