Functional Mitral Regurgitation Research Articles

Abstract 4137175: Functional Mitral Regurgitation as a Predictor of Atrial Fibrillation Recurrence Following Catheter Ablation: A Systematic Review and Meta-Analysis

Background: Recent studies showed that functional mitral valve regurgitation (FMR) was associated with higher long-term mortality in chronic heart failure patients and poorer outcomes in those with atrial fibrillation (AF), including a higher risk of atrial cardiomyopathy. However, the effect of baseline FMR on outcomes post-AF catheter ablation remains unclear due to inconsistent evidence. Methods: We systematically reviewed studies from Medline and EMBASE databases from inception to April 2024. Eligible studies must report the association between baseline FMR and risk of AF recurrence post-AF catheter ablation compared to individuals without FMR. Relative Risk (RR) or hazard ratio (HR) and 95% CIs were retrieved from each study and combined using the generic inverse variance method. Results: Our meta-analysis included 7 cohort studies and found that baseline FMR was associated with a higher risk of AF recurrence compared to those without FMR. The pooled risk ratios (RR) were 1.40 (95% CI 1.11-1.78, I2 = 31%, p = 0.005). No publication bias was identified on the funnel plot. Conclusions: Our pooled analysis found that patients with FMR who underwent AF catheter ablation had a higher risk of AF recurrence compared to those without FMR. Further research is needed to explore the underlying mechanisms and their clinical implications. Keyword: Functional mitral regurgitation, Atrial fibrillation, Catheter ablation, Atrial fibrillation recurrence, Systematic review, Meta-analysis

Abstract 4144585: Association of renal function with mortality and heart failure hospitalization rates after Transcatheter Mitral Valve Edge to Edge Repair

Background: Transcatheter edge to edge repair (TEER) is an established treatment for patients with symptomatic severe functional MR on optimal medical therapy or severe symptomatic primary MR and high surgical risk. Renal dysfunction is associated with adverse outcomes but the threshold at which risks rise are uncertain. Aim To determine the association of estimated glomerular filtration rate (eGFR) with adverse outcomes in patients undergoing TEER for severe symptomatic mitral regurgitation (MR) in Ontario, Canada. Methods: This was a population-based retrospective cohort study using linked administrative datasets of patients who underwent TEER in Ontario, Canada, between 2011 and 2023. The key exposure was eGFR, which was modeled using restricted cubic splines. Outcomes were 1-year mortality, cardiovascular mortality (CV) and heart failure hospitalization (HF). Cause-specific hazards regression was used to model the association between eGFR and outcomes, utilizing eGFR 30ml/min/1.73m2 as the reference value. Results: We studied 2076 patients, of whom 294 (14.2%) had eGFR <30ml/min/1.73m2 and 841 (40.5%) had eGFR 30-60ml/min/1.73m2. The incidence at one year was 16.8% for all-cause mortality, 11% for CV mortality and 14.2% for HF hospitalizations. The Figure illustrates that the predicted incidence of adverse outcomes increases with lower eGFR, with subtle differences in patterns of change in risk at lower eGFR levels such that all-cause mortality and CV mortality begin to rise rapidly at eGFR values ≤30ml/min/1.73m2, while HF hospitalization increases linearly at eGFR ≤50ml/min/1.73m2. Conclusions: There was a progressive increase in all-cause, CV mortality and HF hospitalization after TEER for patients with lower eGFR, particularly those with values <30 ml/min/1.73m2. This data can inform patient discussions and guide post-procedural follow-up.

Qualitative and Quantitative Assessment of Atrial Functional Mitral Regurgitation: analysis from the REVEAL-AFMR registry.

The prevalence, characteristics, and prognosis of atrial functional mitral regurgitation (AFMR) based on severity remain unclear. No studies have systematically evaluated quantitative thresholds, such as effective regurgitant orifice area (EROA) or regurgitant volume, in relation to outcomes in AFMR. This multicenter study aimed to clarify the clinical implications of both qualitative and quantitative assessments of AFMR severity. In this first multicenter study across 26 centers, patients with at least moderate AFMR-defined by preserved left ventricular (LV) function, enlarged left atrium (LA), and absence of primary mitral valve changes-were retrospectively analyzed. AFMR severity was evaluated using a comprehensive approach, including EROA, regurgitant volume, and regurgitant fraction. Among 1,007 patients, 728 (72.3%) had moderate, 146 (14.5%) moderate-to-severe, and 133 (13.2%) severe AFMR. Age, sex, natriuretic peptide levels, and LV ejection fraction were similar across all groups. Patients with severe AFMR had longer atrial fibrillation history, worse heart failure symptoms, larger LV and LA, and more severe tricuspid regurgitation. AFMR severity was independently associated with a higher risk of death, heart failure hospitalization, and mitral valve intervention (HR 1.51, p=0.001 for moderate-to-severe, 2.80, p<0.001 for severe). Quantitative thresholds showed a significantly higher event risk with EROA ≥0.30, regurgitant volume ≥60 mL, and regurgitant fraction ≥50%. Severe AFMR was common and linked to greater atrial fibrillation burden, cardiac structural issues, and an increased risk of adverse clinical events. Quantitative thresholds offer valuable guidance for clinical decision-making and treatment planning.

Biological plausibility and implications of obesity associated valvular heart diseases

Obesity contributes to the development and progression of cardiovascular risk factors and diseases, but so far not much attention has been given to obesity and valvular heart disease. Several observational and mendelian randomization studies have reported an association between body mass index with aortic valve stenosis, but also with secondary functional mitral regurgitation and tricuspid regurgitation in a more indirect manner. Several mechanisms can lead to the link between obesity and valvular heart diseases: left ventricular dilation, as obesity directly contributes to ischemic heart disease and ventricular remodeling, atrial myopathy as well as atrial remodeing and arrhythmias, such as atrial fibrillation, that predispose to valvular regurgitation, but also pulmonary hypertension, which could be the consequence of obesity-related inflammation, insulin resistance, and oxidative stress, valvular calcification which is often associated with adiposity and as a direct effect of increased epicardial adipose tissue and pericardial restraint. Individuals with obesity associated valvular heart disease may experience worse symptoms, quality-of-life, exercise capacity, and risk for adverse outcomes. The effect of and the mechanism for various vavular heart diseases in relation to obesity has not been investigated in depth. Recently, incretin-based drugs and sodium-glucose cotransporter-2 inhibitors have been shown to reduce adiposity, and improve HF outcomes; however, the implications of these drugs on valvular heart diseases have not been evaluated. With innovations in therapies for obesity, several questions merit discussion. Considering the prevalence of obesity and its association with valvular heart diseases, not studying these common comorbid conditions represents a significant missed opportunity.

Commentator Discussion: Durability of annuloplasty in patients with atrial functional mitral regurgitation associated with atrial fibrillation

Commentator Discussion: Durability of annuloplasty in patients with atrial functional mitral regurgitation associated with atrial fibrillation

Cutting-Edge Echocardiographic Tools for Enhanced Understanding and Management of Atrial Functional Mitral Regurgitation.

Cutting-Edge Echocardiographic Tools for Enhanced Understanding and Management of Atrial Functional Mitral Regurgitation.

Weekly Journal Scan: RESHAPing potential treatment indications for functional mitral regurgitation in heart failure.

Weekly Journal Scan: RESHAPing potential treatment indications for functional mitral regurgitation in heart failure.

The prognostic role of left atrial mechanics but not left ventricular function in functional mitral regurgitation

Abstract Introduction When atrial dilatation or ventricular dysfunction underline the development of functional mitral regurgitation (FMR), FMR has been categorized into ventricular and atrial type. Due to limited evidence of surgical correction, majority of patients with FMR were left untreated. We therefore investigated the clinical outcomes related to different phenotypes of FMR and the prognostic factors. Methods Subjects with severe or moderate to severe FMR, diagnosed by transthoracic echocardiography were eligible for this analysis. Three phenotypes of FMR, including atrial, ischemic and ventricular FMR were then classified. The left atrial (LA) strain and left ventricular (LV) global longitudinal strain (GLS) were measured. The study population were followed for a year. Results A total of 298 subjects (mean age 72.3 ± 14.0 years; 68% male) were enrolled, including 165 subjects of ischemic-type FMR (iFMR), 77 subjects of non-ischemic ventricular-type FMR (vFMR), and 56 subjects of atrial-type FMR (aFMR). The baseline characteristics, including age, gender, demography, and morbidities were similar between three groups, but aFMR group had higher LA reservoir strain and better LV GLS. During a mean follow-up duration of 283 days, there were 50 (17%) cases died within the first year. The Kaplan Meier curve analysis showed similar survival rate between three phenotypes of FMR. Body mass index (BMI), systolic blood pressure, diastolic blood pressure, history of myocardial infarction (MI), RV dysfunction, and a lower LA reservoir strain, but not LV GLS were crudely related to one-year mortality. In the multivariable Cox proportional regression analysis, LA reservoir strain was independently predictive of mortality (Hazard ratio for 1% increase and 95% confidence intervals: 0.943, 0.895-0.994). Conclusions Patients with aFMR also have despaired clinical outcomes as patients with vFMR or iFMR. LA reservoir function but not LV systolic function was predictive of worse clinical outcomes. The results may encourage the transcatheter therapy, approved for ventricular-type FMR, for the treatment of aFMR.Kaplan Meier curve analysisMultivariable CPH regression model

ECG as a screening tool for detection of significant functional mitral regurgitation in patients with left bundle branch block

Abstract Background Functional mitral regurgitation (FMR) may occur in the left bundle branch block (LBBB) due to mechanical left ventricular (LV) dyssynchrony, by the imbalance between the tethering and the closing forces exerted on the mitral apparatus1-3. Progressive FMR and LV remodeling result in a reciprocal worsening downward spiral and worse clinical outcomes1-3. Therefore, timely screening and follow-up of these patients to prevent the irreversible progression of FMR is required. To date, only LBBB morphology and QRS duration have been proven predictors of FMR4. Purpose This study aimed to assess the relationship between ECG parameters of LV dyssynchrony and the severity of FMR in patients with LBBB. Methods We retrospectively included 154 consecutive patients with LBBB, in sinus rhythm, who had an echocardiogram, with no more than mild organic valvular heart disease. We measured the following intraventricular dyssynchrony markers: LV activation times (LVAT), intrinsicoid deflection (ID) in lateral and aVF leads and a newly defined marker – the difference (Diff) between aVL and aVF ID’s (Diff_IDaVL_aVF). These two leads record the electrical activation of the two opposing myocardial segments adjacent to the posteromedial and anterolateral papillary muscles, respectively5 (Figure 1). Based on the severity of FMR, the patients were divided into two groups: no/mild FMR (grade II or less) (61%), and significant FMR (grade III and IV) (39%). Results In patients with significant FMR, the LVAT measured in lateral leads, the IDaVL and Diff_IDaVL_aVF were significantly longer, but IDaVF was significantly shorter compared to patients with no/mild FMR (p&amp;lt;0.001). Of all studied ECG parameters, the Diff_IDaVL_ aVF was the parameter that had the strongest correlation with significant FMR (r correlation coefficient 0.82, p &amp;lt; 0.001). In multivariable analysis the Diff_IDaVL_aVF (p = 0.010) was the only parameter independently correlated with significant FMR. On ROC analysis the best cut-off for significant FMR prediction was 55 ms (AUC of 0.99, sensitivity 90% and specificity 97%) (Figure 2). Conclusions In LBBB, a simple intraventricular dyssynchrony ECG parameter can provide insights into FMR severity. A 55 msec Diff_IDaVL_aVF identifies significant FMR that may benefit from early medical or CRT treatment to avoid progression and worse prognosis.

Atrial and ventricular mitral regurgitation in the general population

Abstract Background Functional mitral valve regurgitation (FMR) is the result of two concurrent pathomechanisms: (1) the dilatation of mitral valve annulus (atrial) or (2) remodelling of the left ventricle (ventricular) in the absence of relevant leaflet degeneration¹. Even though FMR has been reported to be the most common cause of relevant MR², there is no general accepted definition of the two subtypes, nor are there population-based data regarding their prevalence, distribution and risk profiles¹. Purpose We aimed to evaluate the prevalence of FMR and to provide an in-depth characterisation of the subtypes aFMR and vFMR in the general population. Methods The study included the first 10,000 participants of the population-based Hamburg City Health Study enrolled between 2016 and 2019. Of these, 8.543 echocardiographic samples were available for analysis. Mitral valve was assessed by two independent investigators. Isolated degenerative MRs as determined by valve mobility (prolapse or restrictive) were excluded. FMR was classified as ventricular when fulfilling one of the following criteria: history of myocardial infarction or coronary artery disease, left ventricular ejection fraction (LVEF) ≤ 40%, restrictive leaflet, tenting area ≥ 150 mm² or coaptation depth ≥ 10 mm. All FMR with LVEF &amp;gt; 55% were classified as atrial. Results After excluding the samples with an insufficient image quality or missing data and re-assessment by the second investigator, 216 of 282 participants with a relevant MR (i.e. moderate or severe) remained (2,6% of the total cohort, see figure 1). In the next step, 153 participants were classified as pure FMR (68.9%), the remaining were mainly functional with minor degenerative features. A total of 31 (14.4%) MRs were classified as vFMR, the remaining 185 participants had an aFMR. Female gender was significantly more common in the aFMR cohort. The remaining demographic variables (age, body mass index) as well as established cardiovascular risk factors (i.e., diabetes, smoking, hypertension) were comparable between the vFMR and aFMR cohort. However, vFMR patients had significantly higher levels of NT-proBNP or NHYA state and presented more frequently with an atrial fibrillation (see figure 2). LVEF and LV stroke volume, TAPSE, left atrial ejection fraction and E/A ratio as a parameter of diastolic dysfunction were lower in the vFMR cohort whereas tenting area and left atrial endsystolic volume was significantly increased. Conclusion In our population-based study, aFMR was found to be the predominant subtype of FMR. The established cardiovascular risk factors were comparable in the vFMR and aFMR cohort. Echocardiographic variables differed significantly and indicate more advanced heart failure and LV remodelling in the vFMR cohort. Further categorization of FMR, in particular regarding the prognostic impact and long-term outcomes, is strongly warranted to allow a clinically relevant definition of aFMR and vFMR.Figure 1:Overview of sample sizeFigure 2:Baseline characteristics

Prognostic implications of guideline-directed medical therapy in functional mitral regurgitation: a meta-analysis

Abstract Background Randomized evidence of the role of heart failure medical therapy for patients with functional mitral regurgitation (FMR) is lacking. Purpose The present meta-analysis sought to investigate the independent long-term prognostic impact of the different medical categories recommended in heart failure, for subjects with FMR. Methods A systematic literature review was conducted in electronic databases to identify studies reporting the association of renin angiotensin system inhibitors (RASi), beta-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) with outcomes in FMR. A random-effects meta-analysis was conducted to quantify the unadjusted and adjusted hazard ratios [(a)HRs] for all-cause death and the composite outcome in each medical category. Results The final sample comprised 12 studies with 6,715 FMR patients (Picture 1). The use of RASi and BBs was associated with a significantly lower risk for all-cause mortality (HR 0.52 [0.39-0.68]; p &amp;lt;0.00001, I2 =62 % and HR 0.62 [0.49-0.77]; p &amp;lt;0.0001, I2 =44 % respectively) and for the composite outcome (HR 0.54 [0.44-0.67]; p &amp;lt;0.00001, I2 =33 % and HR 0.62 [0.52-0.75], p &amp;lt;0.00001, I2 =35% respectively) in unadjusted models (Picture 2). Both RASi (aHR 0.73 [0.56-0.95], p =0.02, I2 =52%) and BBs (aHR 0.60 [0.41-0.88], p = 0.009, I2 =55%) retained their association with the composite outcome in pooled adjusted models (Picture 2). The prognostic benefit of using RASi or BBs was retained in subgroup analysis including only patients with moderate of severe FMR. MRAs did not demonstrate a significant association with improved outcomes in FMR. Conclusions RASi and BBs appear to have a favorable prognostic impact in patients with FMR, regardless of regurgitation severity.Study flow chart for study selectionPharmacotherapy and prognosis in FMR

Significance of mitral annulus apparatus morphometry in patients with persistent atrial fibrillation

Abstract Background Few data about mitral valve apparatus components deformation in patients with persistent atrial fibrillation are available. Four-dimensional transesophageal echocardiography (4DTEE) is an ideal imaging technique to evaluate the complex morphology of the mitral valve apparatus. Purpose The study aimed to find some characteristics in patients presenting with persistent atrial fibrillation and if some of them could be indicative of relapse after cardioversion. Methods The study enrolled 133 patients with persistent atrial fibrillation and mild/moderate functional mitral regurgitation (FMR) before cardioversion. 101 of the patients were at the first persistent atrial fibrillation episode, and 32 with relapse. After performing two-dimensional transthoracic echocardiography (2DTTE), the study included only patients with mild/moderate FMR. 4D TEE permitted a detailed examination of the mitral annulus and valve leaflets, using an E95 machine for acquisition and an ECHOPAC 204 for image postprocessing with mitral valve quantification (MVQ) software. The studied measured: annulus area (AA)3D, annulus perimeter (AP), antero-posterior diameter (APD), posteromedial-anterolateral diameter (PM-ALD), commissural diameter (CD), inter-trigonal distance (ITd), non-planar angle (NPa), mitral-aortic angle (MAa), and for the leaflets, morphological measured parameters were: anterior leaflet area (ALA), posterior leaflet area (PLA), anterior leaflet length (ALL), posterior leaflet length (PLL), anterior leaflet angle (ALa), posterior leaflet angle (PLa), tenting height (TH), tenting area (TA), tenting volume), closure line length (CLL). Results 1. We found significant statistic differences between mitral annulus apparatus components in patients with (32) and without relapse (101) after initial cardioversion: AA 3D: 3.12 vs. 11.65 (p=0.003), AP: 13.23 vs. 12.1 (p=0.0001), APD: 3.76 vs. 3.45 (p=0.0003), PM-ALD: 4.21vs 3.93 (p=0.004), CD:4.17 vs. 3.89 (p=0.002), ITd: 2.82 vs 2.74 (p=0.2), NPa: 158.5 vs 155.2 (p=0.09), MAa: 122 vs 120,7 (p=0.5), ALA: 5.73 vs. 5.18 (p=0.006), PLA: 7.04 vs. 6.09 (p &amp;lt; 0.0001), ALL: 2.19 vs. 2.07 (p=0.036), PLL: 1,73 vs. 1,6 (p=0.03), ALa: 15.31 vs. 18.82 (p=0.002), PLa: 21.38 vs. 25.31 (p=0.01), TH: 0.83 vs. 0.63 (p=0.001), TA: 1.63 vs. 1.32 (p=0.007), TV: 2.75 vs. 2.13 (p=0.007). 2. We found correlations between mitral valve leaflets area and coaptation length in atrial fibrillation patients with (ALA: r=0.72, PLA r=0.65) and without relapse. (ALA: r=0.76, PLA r=0.64). Conclusions 1. 4D TEE identified a more significant mitral annulus and leaflet remodeling in atrial fibrillation patients with relapse after initial cardioversion than in atrial fibrillation patients admitted with a first atrial fibrillation episode. 2. Mitral valve leaflets area correlated with the coaptation length. 3. Mitral annulus complex morphology in patients with atrial fibrillation could be essential in predicting relapse after initial cardioversion.Mitral annulus parameters evaluationMitral leaflets parameters evaluation

Tricuspid regurgitation in atrial fibrillation: correlation to left atrial myopathy and improvement post ablation

Abstract Background Atrial fibrillation (AF) closely correlates to left atrial (LA) myopathy, which in turn can cause functional mitral regurgitation (FMR). The correlation of LA myopathy to tricuspid regurgitation (TR) is still unknown. Data on the dynamic change of TR post AF ablation is still limited. Purpose We sought to investigate the correlation of LA myopathy to TR and furthermore if TR can be improved by AF ablation. Methods Consecutive patients presenting for first time AF ablation were prospectively enrolled. All patients underwent transthoracic echocardiography at baseline as well as 6 months after the ablation procedure. TR was graded as follows: minimal, mild, moderate and severe (I-IV). All study participants underwent high density bipolar voltagemaps prior to AF ablation to characterize the presence of atrial myopathy. Results Our final study cohort consisted of 143 patients (age 64±11 years, 47% female, 48% persistent AF). 15% had no, 21% minimal, 35% mild, 19% moderate and 9% severe TR, respectively. High density maps with 1325±736 mapping points and with an average bipolar voltage of 1.58±0.89mV were created. A significant decline of average LA bipolar voltage was obvious, when comparing patients without TR to any severity level of TR (p=0.015) (Figure 1), however there was no significant difference in LA bipolar voltage, when comparing different TR severity levels (Figure 1). After a follow up of 6 months a significant improvement of TR was observed (p&amp;lt;0.001) with a median level of improvement by one level. 27% had no, 21% minimal, 31% mild, 18% moderate and 2% severe TR, respectively. Conclusion In patients presenting for AF ablation TR closely correlates with LA myopathy according to decreased levels of LA bipolar voltage. AF ablation results in highly significant TR level improvement.

Predictors for mitral regurgitation improvement in patients with pure severe aortic regurgitation undergoing transcatheter aortic valve replacement: when can kill two birds with one stone?

Abstract Objective Transcatheter aortic valve replacement (TAVR) has been recognized as a significant treatment for pure severe aortic regurgitation (PSAR). Part of patients with PSAR concurrently suffer from functional mitral regurgitation (FMR). Whether TAVR could improve FMR in patients with PSAR and the predictors have not yet been clarified. This study aims to explore predictors of FMR improvement in patients with PSAR undergoing TAVR and subsequently provide evidence for further clinical therapy. Method Patients with PSAR and FMR who underwent TAVR at Zhongshan Hospital Affiliated with Fudan University were enrolled from June 2021 to August 2023. Depending on whether FMR improved one month post-TAVR, they were divided into groups with or without FMR improvement. The baseline data, imaging results, and follow-up data of the patients were collected. Result This study included 75 patients, among whom 38 patients had improved FMR and 37 patients did not. Compared to patients without FMR improvement, more patients in the FMR-improved group were diagnosed with renal insufficiency (10.8% vs. 0%, p=0.018), left bundle branch block (8.1% vs. 0%, p= 0.037), and less right bundle branch block (0% vs. 10.5%, p=0.017). The transthoracic ultrasound examination showed that patients with FMR improvement were prone to have lower left ventricular ejection fraction (LVEF) and larger left ventricle end dimension diastole (LVEDd). A higher proportion of patients in the FMR-improved group were found to have had more moderate to severe FMR (28.9% vs. 2.7%, P=0.029). In both groups, the degree of aortic regurgitation was significantly improved during the 1-day and 1-month follow-ups post-TAVR (p&amp;lt;0.001). No significant differences were found in the incidence of postoperative adverse events between the two groups during the short-term follow-up. Conclusion FMR improvement is observed in approximately half of PSAR patients undergoing TAVR. A higher FMR degree, lower LVEF, and hypertension before TAVR are independent predictors of FMR improvement.Figure 1 AR and MR post TAVRTable 1 Logistic regression

Machine-learning phenotyping of patients with functional mitral regurgitation undergoing transcatheter edge-to-edge repair - the MITRA-AI study

Abstract Background Severe functional mitral regurgitation (FMR) may benefit from transcatheter mitral valve repair (TMVR), but selection of patients remains to be optimised. Objectives The aim of this study was to use Machine-Learning (ML) approaches to uncover concealed connections between clinical, echocardiographic, and hemodynamic data associated with patients' outcomes. Methods Consecutive patients undergoing TMVR from 2009 to 2020 were included in the MITRA-AI registry. Eleven relevant clinical and echocardiographic variables were selected in a clustering-based model. The primary endpoint was a composite of cardiovascular death or heart failure hospitalisation at one year, while its single components were secondary endpoints. External validation was performed on the Mitrascore dataset and comparison between clustering and Mitrascore was performed with Net Reclassification Index (NRI). Moreover cluster assignment was performed also on a cohort of patients with moderate-to-severe MR treated with medical therapy alone. Results 822 patients were included in the derivation cohort. The composite primary endpoint occurred in 250 (30%) patients. Four clusters with decreasing risk of the primary endpoint were identified (42%, 37%, 25% and 20% from cluster 1 to cluster 4, respectively). Clusters were combined into a high-risk (clusters 1 and 2) and a low-risk phenotype (clusters 3 and 4). High-risk phenotype patients had larger LVs (&amp;gt; 107 ml/m2), lower LVEF (&amp;lt; 35%) and more prevalent ischemic aetiology (51% to 60% vs. 30% to 40%) compared to low-risk phenotype patients. Moreover, within the high-risk group, patients with diabetes mellitus and with advanced age were at increased risk. Within the low-risk group, ischemic aetiology increased the risk of cardiovascular death, while permanent atrial fibrillation amplified that of HF hospitalizations. In the Mitrascore validation cohort of 1119 patients, incidence of the primary end point varied consistently (48%, 52%, 35% and 42%). Clustering achieved a NRI in 27% of the patients in the derivation cohort and 7% in the validation group compared to Mitrascore. In the validation group of 207 patients treated medically, the incidence of the primary endpoint decreased from the first to the fourth cluster (53%, 42%, 30% and 30%). Conclusions A ML analysis identified meaningful clinical phenotypic presentations in FMR undergoing TMVR, with significant differences in terms of cardiovascular death and heart failure hospitalizations, confirmed in an external validation cohort. ML phenotyping also discriminated prognosis of medically treated patients with severe MR.Central Figure

Presence of Atrial Fibrillation (AF) is a poor prognostic marker in patients with Heart Failure with reduced Ejection Fraction (HFrEF) and Left Bundle Branch Block (LBBB)

Abstract Background Observational data indicate that between 20-30% of patients with HFrEF have LBBB. While numerous independent variables are implicated in the overall prognosis of these patients, this group of patients respond poorly to medical therapy. Presence of AF further impairs the functioning of the left ventricle by several mechanisms e.g., left atrial dilatation, decreased left ventricular filling, irregular cycle length, functional mitral regurgitation etc. Literature is sparse on the cumulative effect of AF in this group of patients. Purpose To assess the effect of AF on left ventricular ejection fraction (LVEF) and mortality in patients presenting with HFrEF and LBBB Methods Single centre, retrospective, observational study over 33 months (Jan 2021 – Sept 2023). Patients with HFrEF and LBBB (as defined by the European Society of Cardiology, 2021) identified from the heart failure database. Results (Table) N=80 Whole cohort: age 74.8 +/- 13.6 years (median:79, range 39-96); 57/80 (67.5%) males. Hypertension [41/80 (51.3%)] was most common comorbidity. Majority were on 3 drugs (23/80, 28.8%) of guideline directed medical therapy (GDMT) with ~1 in 4 patients [19/80 (23.8%)] on all 4 drugs. 32/80 (40.0%) were in AF, remainder in sinus rhythm (SR). Mean baseline LVEF: 21.8 +/- 8.4. Mean LVEF continued to be ≤35% (paired echocardiograms available in 50.0% patients) inspite of GDMT. The QRS duration continued to prolong on follow-up. Patients in AF were statistically significantly older, were less often on all 4 GDMT drugs (particularly sodium glucose transporter 2 inhibitors - SGLT2i’s), and were less likely to survive than those in SR. No difference in comorbid conditions or QRS prolongation on follow-up were seen between patients with AF versus SR. There was trend towards a larger increase in mean LVEF in patients with SR than AF. Conclusions In our experience, patients with HFrEF and LBBB continue to have a high mortality (45.0% at ~ 3 years) inspite of GDMT. AF is seen in a high percentage of patients (40.0%) in this cohort, worsening the prognosis further, with mortality nearly 3 times higher than those in SR. Aggressive management of patients with HFrEF and LBBB with, where indicated, early cardiac resynchronisation therapy (CRT) and more so, of those with AF (with +/- atrioventricular node ablation or left atrial ablation) should be considered at an early stage after diagnosis.Table

DPdT &amp;gt;1200ms predicts greater and sustained drop in ejection fraction post mitral TEER

Abstract Background The maximum rate of left ventricular pressure rise (dP/dTmax) using a CW Doppler from a mitral regurgitation (MR) curve is a simple technique which can estimate myocardial contractility, with "normal" values &amp;gt;1200ms. This technique has not been applied to patients undergoing mitral transcatheter edge-to-edge repairs (M-TEER). Purpose Assess if dP/dT can predict post-procedural ejection fraction (EF). Methods A retrospective review of all M-TEER's performed from January 2011 – February 2023 at a single cardiac centre with an adequate MR CW Doppler to calculate the dP/dT as well as a subsequent TTE at the institution were included. An early TTE (performed day 1-50, average 34.9) and late TTE (goal 1 year, average 354 days) were recorded. Results A total of 155 M-TEER procedures were performed; 66 for degenerative MR (DMR), 11 for atrial functional MR (AFMR) and 78 for ventricular functional MR (VFMR). Baseline characteristics: overall EF 47.9% (DMR 61%, AFMR 52% and VFMR 32%). Age DMR 75.8y, AMFR 78.9y, VFMR 75.6y), overall 31.6% female (DMR 34.6%, AFMR 45.5%, VFMR 25.8%). Surprisingly the DMR cohort demonstrated a significant drop in EF post M-TEER of 5.1% (p&amp;lt;0.001, figure 1). This was most marked in the group with "normal" dP/dT of &amp;gt;1200ms (figure 2, DMR EF drop 7.8% p&amp;lt;0.001). This cohort remained at the new, lower value on follow up (figure 2). The EF in the VFMR remained severely impaired despite M-TEER (figure 1). There was no significant difference between EF pre or early post (p= 0.86). When divided into groups according to baseline dP/dT. The greatest drop in EF was again seen with an apparently normal dP/dT of &amp;gt;1200ms (figure 2). Conclusion "Normal" dP/dT of &amp;gt;1200ms in patients undergoing M-TEER is likely a marker of hyper-contractile LV function as a compensatory mechanism, and may predict a greater fall in EF post correction of MR.

Impact of mitral transcatheter edge-to-edge repair in patients with advanced heart failure evaluated for heart transplantation

Abstract Background Heart transplantation is sometimes the only therapeutic option in patients with advanced heart failure (HF), impaired ventricular function and significant functional or secondary mitral regurgitation (MR). The shortage of organs and the limitations of the recipient make it necessary to consider other therapeutic alternatives in these patients, such as mitral transcatheter edge-to-edge repair (M-TEER). The MitraBridge registry has recently been published in which they analyze the potential effect of M-TEER in patients with advanced HF and moderate-severe MI who are candidates for heart transplantation (mean age 59 years, left ventricular ejection fraction (LVEF) 27%); after a mean follow-up of 24 months, complete in 82.4%, they report an overall survival of 78.5%, a combined event-free survival of 47%, with a 6.5 % need for urgent transplantation and an HF hospitalization rate after M-TEER of 44/100 patient-years. The aim of our study is to assess the impact of M-TEER on mortality and the combined events of death, HF rehospitalization and the need for urgent transplantation or a ventricular assistance device in patients with moderate-severe functional MI and advanced HF who have also been evaluated for cardiac transplantation in our hospital. Methods This is a retrospective analysis of a prospective registry. Of the patients treated by M-TEER for severe MI, we selected those with advanced HF (defined as LVEF≤35%, and/or advanced functional class (NYHA III-IV)) who had also been evaluated as possible candidates for inclusion in the heart transplant list. Results From November 2011 to December 2023, 191 patients were treated by M-TEER, of whom 38 patients met the established criteria (median age 59 years [48-65], 31 (81%) males, mean LVEF was 26 ± 6%). All patients had at least one previous hospitalization for HF and optimal medical treatment according to guidelines; the rest of the baseline clinical characteristics are listed in Table 1. During the follow-up after M-TEER, with a median of 34 months [7-70], the probability of overall survival at 2 years was 75.6%. The combined endpoint of death, need for urgent transplantation or a ventricular assist device, and rehospitalization for heart failure occurred in 26 patients with a 2-year event-free survival probability of 48% (Figure 1). Five patients (13%) were transplanted, one (2.6%) urgently. Prior to M-TEER therapy, the rate of HF hospitalization was 108 hospitalizations/100 patient-years, which was significantly reduced after the procedure to 33 hospitalizations/100 patient-years (rate ratio 0.31 [95% CI 0.21-0.45, p&amp;lt;0.0005]). Conclusions In patients with advanced HF and severe functional MR who are candidates for cardiac transplantation, M-TEER is an effective therapeutic alternative, achieving a survival rate of more than three-quarters of the patients at 2 years of follow-up, a significant reduction in HF hospitalizations, and a low rate of need for cardiac transplantation.

Transcatheter mitral edge-to-edge repair in patients with prior cancer diagnosis

Abstract Background Transcatheter edge-to-edge repair (TEER) is a safe and effective therapy for mitral regurgitation (MR). Despite oncological patients have an increased risk of functional and organic MR due to cardiotoxic treatment exposure, the use of TEER in this setting remains underexplored. Purpose To evaluate the safety and efficacy of TEER in patients with MR and prior cancer diagnosis. Methods Observational, retrospective, multicenter study based on the Spanish national TEER registry. Patients from those centers providing oncological specific data were included in this analysis. Patients with and without history of cancer were propensity score matched (PSM) in a 1:1 ratio. The primary efficacy outcome was a composite of death from any cause or unplanned hospitalization for heart failure at 1 year. Results A total of 1237 patients with MR who underwent TEER between 2010 and 2022 across 14 centers in Spain were included. The mean age was 73 ± 11 years and 34% were female. MR etiology was functional in 58%, organic in 27% and mixed in 15%. Of them, 164 had a history of cancer. Baseline characteristics of the unmatched cohort are shown in Figure 1. Median time from cancer diagnosis to TEER was 7 (3-17) years and the most common cancer types were breast (20%), leukemia/lymphoma (19%) and colorectal (11%). PSM resulted in 163 pairs with a good balance of baseline characteristics (Figure 1). Procedural success rate was high and similar between the groups (93% vs 96%, p=0.217), as were periprocedural complication rates (Figure 2A). The primary efficacy endpoint occurred in 38 (23%) patients in the cancer group and 29 (18%) patients in the control group (Hazard ratio 1.36, CI 95% 0.84 to 2.20, p= 0.214) (Figure 2B). Conclusion In routine practice, a notable proportion of patients undergoing mitral TEER have a prior cancer diagnosis. Immediate and 1-year clinical outcomes appear comparable to those observed in non-cancer patients. These findings suggest that mitral TEER should not be withheld from this growing population.

Mitral annular dynamics after transcatheter edge-to-edge repair for functional mitral regurgitation: comparison with surgical annuloplasty

Abstract Background Transcatheter edge-to-edge repair (TEER) is a recently emerged therapeutic option for functional mitral regurgitation (FMR). Although the mitral annular shape and function may play an important role in the pathophysiology of FMR, few reports have evaluated the impact of TEER. We sought to investigate the impact of TEER on the mitral annulus and its motion in FMR compared with that of mitral annuloplasty (MAP). Methods Using three-dimensional transesophageal echocardiography, we evaluated the mitral annular morphology and dynamic motion in patients who underwent TEER or MAP before and after the procedures. Mitral annulus analysis was performed by a semi-automatic program to create a dynamic model of the three-dimensional structure, where the end-systolic annular structure was semi-automatically annotated and manually corrected, followed by automatic tracking of the annulus throughout the cardiac cycle . The mitral annular parameters such as mitral annular diameters, area, circumference, and height at all frames were automatically calculated from the model. In order to align the cardiac phase in each patient (i.e. to set the start and the end of diastole and systole at the same time for all patient), data were spline-interpolated to 100 systolic and 200 diastolic frames and then statistically analyzed. The dynamic changes of the parameters during the cardiac cycle were calculated as (maximum – minimum value) / maximum value after the interpolation. Results Patients who underwent TEER (n=20, 69±15 years, 40% female) and those who underwent MAP (n=16, 64±11 years, 6% female) had similar echocardiographic characteristics before the procedures. The maximum anteroposterior diameter and annulus area decreased after both TEER and MAP, while the intercommissural diameter decreased only after MAP but not after TEER. After TEER, the dynamic change in anteroposterior diameter throughout the cardiac cycle tended to decrease (p=0.055), while intercommissural change rather increased (p=0.049), resulting in preserved change in annulus area (p=0.74). After MAP, changes in both diameters and area decreased significantly (all p&amp;lt;0.05). MAP was associated with postoperative mitral annulus area immobility after adjustment (p=0.030). Conclusions The dynamic motion of the mitral annulus in patients with FMR was better preserved after TEER than after MAP. There was a decreasing trend in anteroposterior motion, which was compensated for by intercommissural motion after TEER. Future studies are needed to determine the association of these results with cardiac function and prognosis.