Mitral Regurgitant Research Articles

Transcatheter Mitral Cerclage Ventriculoplasty: From Bench to Bedside.

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

A Novel Approach for Semiautomated Three-Dimensional Quantification of Mitral Regurgitant Volume Reflects a More Physiologic Approach to Mitral Regurgitation

Quantification of mitral regurgitation (MR) by echocardiography is integral to assessing lesion severity and entails the integration of multiple Doppler-based parameters. These methods are founded primarily upon the principle of proximal isovelocity surface area (PISA), a two-dimensional (2D) method known to involve several assumptions regarding MR jet characteristics. The authors analyzed the results of a semiautomated method of three-dimensional (3D)-based regurgitant volume (RVol) estimation that accounts for jet behavior throughout the cardiac cycle and compared it with conventional 2D PISA methods for MR quantification. A total of 50 patients referred for transesophageal echocardiography for evaluation of primary (n=25) and secondary (n=25) MR were included for analysis. Three-dimensional full-volume color data sets were acquired, along with standard 2D methods for PISA calculation. A 3D semiautomated MR flow quantification algorithm was applied offline to calculate 3D RVol, with simultaneous temporal curves generated from the 3D data set. Three-dimensional RVol was compared with 2D RVol. Three-dimensional vena contracta area was also performed in all cases. There was a modest correlation between 2D RVol and 3D RVol (r=0.60). The semiautomated 3D approach resulted in significantly lower values of RVol compared with 2D PISA. Real-time and dynamic flow curve patterns were used for integral estimates of 3D RVol over the cardiac cycle, with a distinct bimodal pattern in functional MR and a brief and solitary peak in primary MR. Using a semiautomated 3D software for the quantification of MR allows the simultaneous calculation of 3D RVol with an automated generation of dynamic flow curves characteristic of the underlying MR mechanism. The present flow curve pattern results highlight well-known differences between MR flow dynamics in degenerative MR compared with functional MR.

Right Ventricular Dysfunction Predicts Outcome in Acute Heart Failure.

AimThe severity of cardiac impairment in acute heart failure (AHF) predicts outcome, but challenges remain to identify prognostically important non-invasive parameters of cardiac function. Left ventricular ejection fraction (LVEF) is relevant, but only in those with reduced LV systolic function. We aimed to assess the standard and advanced parameters of left and right ventricular (RV) function from echocardiography in predicting long-term outcomes in AHF.MethodsA total of 418 consecutive AHF patients presenting over 12 months were prospectively recruited and underwent bedside echocardiography within 24 h of recruitment. We retrospectively assessed 8 RV and 5 LV echo parameters of the cardiac systolic function to predict 2-year mortality, using both guideline-directed and study-specific cutoffs, based on the maximum Youden indices via ROC analysis. For the RV, these were the tricuspid annular plane systolic excursion, RV fractional area change, tissue Doppler imaging (TDI) peak tricuspid annular systolic wave velocity, both peak- and end-systolic RV free wall global longitudinal strain (RV GLS) and strain rate (mean RV GLSR), RV ejection fraction (RVEF) derived from a 2D ellipsoid model and the ratio of the TAPSE to systolic pulmonary artery pressure (SPAP). For the LV, these were the LVEF, mitral regurgitant ΔP/Δt (MR dP/dt), the lateral mitral annular TDI peak systolic wave velocity, LV GLS, and the LV GLSR.ResultsA total of 7/8 parameters of RV systolic function were predictive of 2-year outcome, with study cutoffs like international guidelines. A cutoff of < −1.8 s–1 mean RV GLSR was associated with worse outcome compared to > −1.8 s–1 [HR 2.13 95% CI 1.33–3.40 (p = 0.002)]. TAPSE:SPAP of > 0.027 cm/mmHg (vs. < 0.027 cm/mmHg) predicted worse outcome [HR 2.12 95% CI 1.53–2.92 (p < 0.001)]. A 3-way comparison of 2-year mortality by LVEF from the European Society of Cardiology (ESC) guideline criteria of LVEF > 50, 41–49, and < 40% was not prognostic [38.6% vs. 30.9 vs. 43.9% (p = 0.10)]. Of the 5 parameters of LV systolic function, only an MR dP/dt cutoff of < 570 mmHg was predictive of adverse outcome [HR 1.63 95% CI 1.01–2.62 (p = 0.047)].ConclusionWith cutoffs broadly like the ESC guidelines, we identified RV dysfunction to be associated with adverse prognosis, whereas LVEF could not identify patients at risk.

P224 PRIMITIVE DILATED CARDIOMYOPATHY IN YOUNG MAN NOT ELIGIBLE FOR CARDIAC TRANSPLANTATION: COMBINED USE OF DEFIBRILLATOR, CARDIAC CONTRACTILITY MODULATION (CCM) AND CARILLON

Abstract Acute heart failure refers to rapid or gradual onset of symptoms and/or signs of chronic heart failure due to precipitating factors. Many patients with heart failure progress into a phase of advanced heart failure, characterized by persistent symptoms despite maximal therapy. Prognosis remains poor, with high 1–year mortality. Prognostic stratification is important to identify the ideal time for referral to an appropriate center capable of providing advanced therapies. We present the case of a 36–year–old black homeless man was admitted to Cardiological intensive care unit for acute heart failure complicated by intermediate–high risk bilateral subsegmentary pulmonary embolism, left endoventricular thrombosis, severe biventricular systolic dysfunction and secondary severe mitral insufficiency. After infusional diuretic and anticoagulant therapy, coronary angiography was performed documenting non–obstructive epicardial coronary arteries. Thereafter the therapy with sacubitril/Valsartan was falled, due to marked hypotension. Due to the high risk of sudden cardiac death, a single–chamber ICD was implanted in primary prevention. He was not eligible for long–term mechanical assistance (VAD) implantation and/or heart transplantation from referral centers, because of the patient‘s precarious psychosocial background. Furthermore, in the fullness of his faculties, the patient refused this possibility for religious reasons. Discharged in fair compensation, after resolution of pulmonary embolism and intracavitary thrombosis, he was again hospitalized for an exacerbation of chronic heart failure. Once labile hemodynamic compensation was reached, a cardiac contractility modulation device (CCM) was positioned, with the aim of improving symptoms. After optimization of therapy, with persistence of severe symptoms despite optimal medical and device therapy, options for intervention on the mitral valve were evaluated before further deterioration of the clinical conditions. Since this is a highly symptomatic patient at high risk for surgery, we opted for a coronary sinus mitral annuloplasty repair with Carillon, performed in the absence of complications. At the follow–up there was a mitral regurgitant volume reduction, improvement symptoms, in the absence of further hospitalizations.

Hemodynamic Modeling for Mitral Regurgitation

<h3>Purpose</h3> Mitral regurgitation (MR) is a serious valvular pathology that impacts over 2% of the total population. Despite evidence that MR poses potentially significant risks of RV dysfunction and failure, the risks of MR are mainly assessed based on left heart parameters, including the mitral regurgitant fraction (MRF) and effective regurgitant orifice area (EROA). To elucidate the links between MR and RV dysfunction, we propose a computational fluid dynamic (CFD) modeling pipeline aimed at providing a deeper understanding of the interplay between MR and RV function. <h3>Methods</h3> Dynamic CT data of a spatiotemporal motion of the patient's heart were segmented using a 3D U-Net based neural network. Meshed segmentations were propagated through time using IRTK non-rigid registration and volume preserving surface motion interpolation to recreate the motion of the patient's heart over the cardiac cycle. The 3D model was coupled to a closed loop 0D model that represents the remaining cardiovascular system and provides continuous feedback to the 3D model. This also allows the relationship between the complicated hemodynamics in the left heart and the state of the RV to be modeled. The functionality of the RV is prescribed by defining the stroke volume over the cardiac cycle. Mild, moderate, and severe MR was prescribed by defining the EROA's based on clinical parameters. <h3>Results</h3> We looked at how different MR jet areas (EROA) and RV functions pose risks to the cardiovascular system. Results from this study show that a high RV function reduces MRF at the expense of much higher right ventricle stroke work index (RVSWI) - which is strongly correlated with RV failure (Fig. 1). Variation in EROA has a lower impact on the RF and RVSWI than the RV functionality, but it does change the local hemodynamics (Fig. 2). <h3>Conclusion</h3> This process makes it possible to further understand the effect that MR has on right heart function. This is particularly important for patients who require a left ventricular assist device in which right heart failure, linked with MR, is a recognized complication.

Comparison of Mitral Regurgitant Volume Assessment between Proximal Flow Convergence and Volumetric Methods in Patients with Significant Primary Mitral Regurgitation: An Echocardiographic and Cardiac Magnetic Resonance Imaging Study

Discrepancies have been observed between transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) severity grading in primary mitral regurgitation (MR). We sought to compare mitral regurgitant volume (RVol) determined by the TTE proximal flow convergence (proximal isovelocity surface area [PISA]) method and by volumetric methods (TTE and CMR) and to study the relationship between left ventricle (LV) size and RVol obtained by either the PISA or volumetric methods. Two centers prospectively recruited 188 patients with at least moderate to severe primary MR due to prolapse in sinus rhythm who underwent TTE and CMR examinations. Regurgitant volume was estimated by either PISA (PISA-RVol) or volumetric methods (LV total stroke volume-systolic aortic forward outflow volume) using either CMR (CMR-RVol) or TTE (TTE-RVol). The PISA-RVol was weakly correlated with CMR-RVol and TTE-RVol (r=0.29 and 0.30, respectively; P<.001 for both). On multivariable analysis, smaller CMR-left ventricular end-diastolic volume (LVEDV) and absence of mitral annular disjunction independently correlated with increased magnitude of RVol difference between PISA and volumetric methods. While PISA-RVol and LVEDV were unrelated, CMR-RVol and TTE-RVol moderately correlated with LVEDV (r=0.66 and 0.68, respectively; P<.001 for both). In contrast, LVEDV and regurgitant fraction (RVol/LVtotal stroke volume), assessed with either TTE or CMR, were poorly correlated (r=0.17, P=.02; and r=0.12, P=.10, respectively). Mitral RVol values estimated by PISA and volumetric methods are not directly comparable. The expected proportional relationship between volumetric RVol and LV size, which was not observed with PISA-RVol, suggests that PISA-RVol would be inaccurate. Given that RVol assessed with volumetric methods depends on LV size, determination of a unique RVol threshold for severe MR is challenging. In contrast to RVol, calculating regurgitant fraction by volumetric methods allows the quantification of MR severity independently from LV size.

Comparative study of coronary artery bypass grafting combined with off-pump mitral valvuloplasty versus coronary artery bypass grafting alone in patients with moderate ischemic mitral regurgitation.

Whether mitral surgery should be performed simultaneously with coronary artery bypass grafting (CABG) in patients with moderate ischemic mitral regurgitation (MIMR) is controversial. This study was performed to introduce a method of off-pump mitral valvuloplasty after off-pump CABG (OPCABG) and compare it with OPCABG alone. Eighty-three patients with MIMR underwent OPCABG. Among them, 21 patients (Group A) underwent posterior mitral annuloplasty without cardiopulmonary bypass, and 62 patients (Group B) underwent OPCABG alone. The primary endpoint of follow-up was the mitral regurgitation area. The mean mitral regurgitant area in Group A and B was 6.42 ± 1.02 and 5.49 ± 1.24cm2 preoperatively (p = .479), 2.93 ± 1.35 and 3.28 ± 1.93cm2 at 1week postoperatively (p = .516), 3.06 ± 2.16 and 3.09 ± 1.85cm2 at 3months postoperatively (p = .839), and 3.02 ± 1.60 and 3.7cm2 (median) at 1year postoperatively (p = .043). There was less regurgitation in Group A at the mid-term. Intragroup comparison showed significant differences between the preoperative and postoperative values in both groups, with no difference in the regurgitant area at each postoperative time point in Group A but a significant difference between 3months and 1year postoperatively in Group B (p = .042). Multiple linear regression showed that the mid-term mitral regurgitant area changes were negatively correlated with graft flow and positively correlated with age. In patients with MIMR who underwent OPCABG plus off-pump mitral valve annuloplasty, the mitral regurgitant area was smaller and mitral regurgitation recurrence was less frequent at the mid-term follow-up.

Prognostic significance of peak atrial longitudinal strain in patients with functional mitral regurgitation

Abstract Funding Acknowledgements Type of funding sources: None. Background Chronic mitral regurgitation has been shown to promote left atrial (LA) dysfunction and remodeling. However, the significance of LA dysfunction in this setting has not been fully investigated. The aim of our study was to assess the prognostic impact of peak atrial longitudinal strain (PALS), a surrogate of LA function, in a cohort of patients with LV systolic dysfunction and functional mitral regurgitation (FMR). Methods Patients with at least mild FMR and reduced LVEF (&amp;lt; 50%) under optimized medical therapy who underwent transthoracic echocardiography between 2010 and 2018 were retrospectively identified at a single-centre. FMR grading was undertaken according to the new 2021 valvular guidelines. PALS was assessed by 2D speckle tracking in apical 4-chamber view (as per EACVI current recommendations). Cox proportional hazards regression was applied for univariable and multivariable analysis to investigate the association between clinical and echocardiographic parameters, namely PALS, and all-cause mortality. Results A total of 307 patients (median age 70 years, 77% male) were included. Median LVEF was 35% (IQR: 27 – 40%) and median mitral regurgitant volume was 25mL (IQR: 14 – 34mL). According to the new ESC 2021 valvular guidelines, 32 patients had severe FMR (10%). During a median follow-up of 3.5 years (IQR 1.4 – 6.6), 148 patients died. Median PALS was 14% (IQR 8 – 20%). The unadjusted mortality incidence per 100 persons-years increased with progressively lower values of PALS (figure 1). On ROC curve analysis, the best PALS cut-off value associated with mortality was &amp;lt; 15%. Kaplan-Meier survival curves according to FMR severity and PALS &amp;gt; or &amp;lt; 15% are depicted in figure 2. PALS remained independently associated with all-cause mortality on multivariable analysis (adjusted hazard ratio [aHR]: 0.94; 95%CI: 0.90 – 0.98; p = 0.004) even after adjustment for several (n = 14) clinical and echocardiographic confounders. Conclusion In a cohort of patients with reduced LVEF and functional mitral regurgitation, peak atrial longitudinal strain was associated with all-cause mortality. Abstract Figure 1 Abstract Figure 2

Comparison of mitral regurgitant volume assessment between proximal flow convergence and volumetric methods in patients with significant primary mitral regurgitation

Abstract Funding Acknowledgements Type of funding sources: None. Background. Discrepancies have been observed between transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (MRI) severity grading in primary mitral regurgitation (MR). Purpose. To compare mitral regurgitant volume (RV) obtained by the proximal flow convergence method (PISA) method by TTE and by volumetric methods (TTE and MRI), and study the relationship between LV size and RV obtained by either the PISA or volumetric methods. Methods and results. 188 patients from 2 heart valve clinics with at least moderate-to-severe primary MR due to prolapse in sinus rhythm who underwent evaluation with TTE and MRI were included. RV was estimated by either PISA or volumetric methods (Left ventricular [LV] stroke volume minus systolic aortic outflow volume)) by either MRI (MRI-RV) or TTE (TTE-RV)). PISA-RV and either MRI-RV or TTE-RV weakly correlated (r = 0.29 and 0.30,p &amp;lt; 0.001). On multivariable analysis, LV end-diastolic volume (LVEDV) and bileaflet prolapse independently correlated with the magnitude of the difference between PISA and volumetric methods. While PISA-RV and LVEDV were unrelated, MRI-RV and TTE-RV strongly correlated with LVEDV (r = 0.66 and 0.68,p &amp;lt; 0.001). In contrast, LVEDV and regurgitant fraction (RF = RV/LVEDV) either with TTE or MRI were poorly related (r = 0.17,p = 0.02 and r = 0.12,p = 0.10). Conclusion. RV estimated by the PISA and volumetric methods are not comparable. The expected proportional relationship between volumetric RV and LV size, which is not observed with PISA-RV suggests the inaccuracy of PISA-RV. Given that RV by volumetric methods depends on LV size, determination of a unique RV threshold for severe MR is challenging. Calculation of RF may overcome this limitation. Abstract Figure. RV assessed by PISA or volumetric method Abstract Figure. Illustrative example

Dark-blood late gadolinium enhancement CMR improves detection of papillary muscle fibrosis in patients with mitral valve prolapse

PurposePapillary muscle fibrosis may act as an arrhythmogenic substrate in patients with mitral valve prolapse (MVP). Previous studies used conventional bright-blood late gadolinium enhancement cardiovascular magnetic resonance (LGE CMR) imaging to assess papillary muscle fibrosis, although this technique suffers from poor scar-to-blood contrast which may limit its sensitivity, in contrast to dark-blood LGE. This study sought to compare bright-blood and dark-blood LGE for the detection of papillary muscle fibrosis in patients with MVP. Method60 patients with known isolated MVP referred for CMR were prospectively recruited. A routine CMR protocol was used to obtain cine imaging, dark-blood LGE and bright-blood LGE in three long-axis views and a stack of short-axis views. Flow mapping of the proximal aorta was performed to calculate mitral regurgitant volume. Images were analysed for cardiac volumes, ejection fraction, mitral regurgitation severity, MVP characteristics (mitral annular disjunction, prolapse volume) and presence of LGE at the papillary muscles and myocardium. ResultsDark-blood LGE detected significantly more subjects with LGE at the papillary muscles than bright-blood LGE (35% vs 15%, p = 0.002). There was no difference between LGE techniques regarding myocardial (non-papillary muscle) fibrosis (present in 25% each). No statistical differences were observed between patients with or without LGE at the papillary muscles regarding demographics, clinical data (including ventricular arrhythmia) and MVP characteristics. Furthermore, no association was found between LGE at the papillary muscles and at the myocardium. ConclusionsCompared to bright-blood LGE, dark-blood LGE CMR improves the detection of LGE at the papillary muscles in patients with MVP.

Abstract 9995: Predictors of Functional Mitral Regurgitation Severity in Non-Ischemic Cardiomyopathy

Background: Functional mitral regurgitation is a result of left ventricular and/or atrial remodeling and dysfunction leading to the leaflet malcoaptation, and associated with adverse prognosis. This study assesses the associations between clinical and chamber quantification parameters by cardiac magnetic resonance (CMR) imaging with FMR severity. Methods: This study includes a retrospective cohort of adult NICM patients undergoing CMR during 2002-2017. Quantitative left ventricle, left atrial and right ventricle parameters measured by CMR and clinical factors were assessed for their associations with mitral regurgitant fraction using multivariable linear regression analyses. Results: In 633 NICM patients, mean age was 52.6 years, 256 (40.4%) were female and mitral regurgitant volume and fraction were 11±11 mL and 14±13% respectively. Mitral regurgitant fraction was greater than 20%, 30% and 40% in 26.5%, 11.8% and 6.5% of the cohort respectively. In multivariable linear regression analyses(Table), female sex, higher left-ventricular end-diastolic volume indexed, left ventricular ejection fraction and left atrial volume indexed, and reduced right ventricular ejection were all independently associated with higher mitral regurgitation fraction. Conclusion: FMR is prevalent in NICM patients, and interestingly, female sex and higher left ventricular ejection fraction were independently associated with mitral regurgitation severity, while other predictors include adverse left ventricular and left atrial remodeling, and right ventricular dysfunction.

Abstract 11516: Quantification of Regurgitation Through Dual Orifices: Pulsatile in Vitro Analysis with Echocardiography and MRI Assessment

Introduction: Proximal Isovelocity Surface Area (PISA) measurement is widely accepted to quantify mitral regurgitant volume (RVol), but flow convergence (FC) zones are complicated with dual orifices, seen with mitral clipping. This study seeks to investigate how flow through one orifice affects PISA measurement across the other to better quantify RVol in dual orifice conditions. Methods: 3D-printed dual circular orifice models with varying relative areas were integrated into a pulsatile flow phantom simulating left heart flow. One orifice (A) was standardized at 19.6 mm 2 while the other (B) was 1X, 2X, and 3X the area of A in three models. Inter-orifice distance was 5 mm to emulate mitral clipping. Continuous wave doppler echocardiography measured peak velocity and velocity time integral. PISA was performed at four aliasing velocities normalized to peak velocity (V a /V peak ) (10%, 8%, 4%, 2%) to compute RVol with 2D phase contrast MRI as reference. In each model, PISA RVol and percent error was calculated to see how varying the area of B impacts PISA accuracy of A. 4D flow MRI FC data was also collected to visualize the 3D formation of FC zones. Results: Using a high V a /V peak to create distinct FC zones provides a better RVol estimation with PISA, as low V a /V peak will merge the FC zones, overestimating flow across individual orifices. Single factor analysis of variance (ANOVA) of percent error of A across the three models showed no significant difference at high V a /V peak (8%: p=0.80, 10%: p=0.23), but significant difference at low V a /V peak (2%: p=0.010, 4%: p=0.005). High V a /V peak FC zones of orifices are independent from each other; PISA can be measured with standard practices and added together for an accurate total RVol. At low V a /V peak , FC orifice zones overlap with overestimation error increasing with larger B area. This finding suggests that resolving two separate FC zones to minimize flow interference is important for accurate RVol estimate in a dual orifice setting.

Mechanism of improvement in atrial functional mitral regurgitation after catheter ablation for atrial fibrillation: Three-dimensional analysis using multislice computed tomography.

Several factors associated with atrial functional mitral regurgitation development have been reported; however, geometric changes in the mitral apparatus after catheter ablation for atrial fibrillation have not been sufficiently investigated. This study aimed to clarify what determines improvements in atrial functional mitral regurgitation after sinus rhythm restoration in patients who underwent catheter ablation for atrial fibrillation by using multislice computed tomography. We analysed volumetric multislice computed tomography images of 44 atrial fibrillation patients with significant atrial functional mitral regurgitation (moderate or worse) before and after catheter ablation. We measured the three-dimensional geometry of the mitral apparatus including the mitral annular area and interpapillary muscle distance. We calculated the differences before and after catheter ablation (Δmitral annular area, Δinterpapillary muscle distance) and assessed mitral regurgitation severity based on the mitral regurgitant jet area and its changes before and after catheter ablation (Δjet area) using transthoracic echocardiography. After catheter ablation, the jet area was significantly decreased. The left ventricular ejection fraction was significantly increased and the left ventricular volume had a decreasing trend. The Δjet area was significantly correlated with the Δinterpapillary muscle distance (r = .43; p = .004). The Δinterpapillary muscle distance was the strongest determinant of improvements in atrial functional mitral regurgitation severity (p = .026). Decreased interpapillary muscle distance was strongly associated with improvements in atrial functional mitral regurgitation. Amelioration of left ventricular dysfunction by sinus rhythm restoration might be related to improvements in atrial functional mitral regurgitation after catheter ablation.

Gender differences in primary mitral regurgitant volumes at specific regurgitant fractions as assessed by magnetic resonance imaging.

Guidelines suggest using a regurgitant fraction of 50% and regurgitant volume of 60ml for determination of severe mitral insufficiency. Recent MRI data has suggested that a regurgitant fraction of 40% defines severe primary mitral insufficiency. We sought to determine whether there were gender differences in primary mitral regurgitant volumes for regurgitant fractions of 40% and 50%. A database search identified 394 patients that had MRI with a mitral regurgitant volume ≥ 10ml or a study indication of mitral insufficiency. Chart review identified 97 patients with primary mitral insufficiency. Of these patients, 53 (54%) were women. Men had significantly larger left ventricular volumes, myocardial mass, stroke volumes and mitral regurgitant volumes (37 ± 25ml vs. 24 ± 12ml). The difference in regurgitant fraction between genders was not significant (27 ± 14% vs. 24 ± 11%; p-value = 0.24). Regurgitant fraction and regurgitant volume had a strong linear correlation in both men (r = .95) and women (r = .92). Despite similar linear correlations, the slope-intercept equations differed significantly between men and women (p < .001). A regurgitant fraction of 40% correlated with a regurgitant volume of 59ml in men and 39.5ml in women, while a regurgitant fraction of 50% correlated with a regurgitant volume of 76.2ml in men and 49.6ml in women. Regurgitant fraction, determined by cardiac MRI, provides a gender independent assessment of primary mitral insufficiency, and suggests that regurgitant volume thresholds for severe primary mitral insufficiency may be lower in women.

Impact of aortic valve replacement for severe aortic stenosis on organic and functional mitral regurgitation.

AimsConcurrent mitral regurgitation (MR) influences treatment considerations in patients with severe aortic stenosis (sAS). Limited information exists regarding haemodynamic effects of sAS on MR severity and outcome of these patients. We assessed the impact of aortic valve replacement (AVR) on MR according to mechanism in patients with sAS and MR.Methods and resultsIn patients with sAS who received surgical or transcatheter AVR from 2008 to 2017, those with effective mitral regurgitant orifice area (ERO) ≥ 10 mm2 prior to AVR were evaluated. The change in MR after AVR was considered significant when there was at least one grade difference. We compared the all‐cause mortality of patients with and without improvement in MR. Of 234 patients with sAS and MR (age 80 ± 9 years, 52% male, ERO 19 ± 7 mm2), organic and functional MR were present in 166 (71%) and 68 (29%), respectively. MR improved in 136 (58%); improvement occurred with similar frequency in organic versus functional MR (59% and 57%, P = 0.88). Associated determinants were absence of atrial fibrillation in organic MR [odds ratio (OR) 2.09, 95% confidence interval (CI) 1.00–4.37; P = 0.049] and indexed aortic valve area (iAVA) ≤ 0.40 cm2 in functional MR (OR 3.28, 95% CI 1.13–9.47; P = 0.028). In the overall cohort, mitral annulus diameter < 3 cm (OR 1.74, 95% CI 1.02–2.97; P = 0.041) and QRS duration < 115 ms (OR 1.73, 95% CI 1.00–2.98; P = 0.049) were independently associated with improvement in MR. During median follow‐up of 3.5 years, lack of improvement in MR was not associated with higher mortality in the overall cohort of patients with ERO ≥ 20 mm2 [adjusted hazard ratio (HR) 1.71, 95% CI 0.90–3.27; P = 0.10, adjusted for age, New York Heart Association III or IV, diabetes, and creatinine ≥ 2.0 mg/dL]. Lack of improvement in organic MR was associated with higher mortality (adjusted HR 3.36, 95% CI 1.40–8.05; P < 0.01). In patients with functional MR, change in MR was not associated with mortality (HR 1.24, 95% CI 0.44–3.47; P = 0.68).ConclusionsIn nearly 60% of patients with sAS and MR, MR improved after AVR, even in the majority of patients with organic MR. Absence of atrial fibrillation in organic MR, iAVA ≤ 0.40 cm2 in functional MR, and mitral annulus diameter < 3 cm and QRS duration < 115 ms in the overall population were associated with MR improvement. Post‐operative improvement in organic MR was associated with better survival.

Disproportionate mitral regurgitation is associated with survival in acute heart failure with moderate range ejection fraction

Abstract Background In acute heart failure (AHF) with moderate-range ejection fraction (HFmrEF) the effect of mitral regurgitation (MR) is uncertain. Methods 103/440 consecutive patients in AHF had HFmrEF. They underwent bedside echocardiography within 24 hours of recruitment, prior to offloading, and were followed up for 2 years. The endpoint was all-cause mortality at 2 years. A novel proportionality index - where the effective regurgitant orifice is divided by the left ventricular end-diastolic volume (ERO/LVEDV)) - identified HFmrEF patients with disproportionate MR. Results 103/440 (23.4%) patients had HFmrEF with an average EF of 44.6±2.6%. 54.4% were male, with an average age of 80.5±11.4. 47.6% had a previous diagnosis of hypertension, 28.2% diabetes and 10.7% cerebrovascular disease. Patients did not present in shock, with average systolic/diastolic blood pressures of 141.7±26.2mmHg/ 78.5±19.3mmHg, nor did they primarily present with severe infections with mean CRP of 23.2±31.7. BNP at presentation was 1179.8±1028.5ng/L. Every patient had MR, 78/103 (75.7%) had MR quantifiable by PISA. 54/78 (69.2%) had disproportionate MR, defined by an ERO/LVEDV &amp;gt;0.14mm2/ml. When compared to proportionate MR, disproportionate MR in HFmrEF was associated with: greater LVEDV (136.3±53.6ml vs. 103.3±39.7ml [p=0.018]), greater mitral regurgitant volumes (41.8±18.5ml vs. 21.5±12.5ml [p&amp;lt;0.001]) and systolic pulmonary artery pressures (60.2±21.0mmHg vs. 48.0±14.7mmHg [p=0.012]) but not left-atrial size (30.2±7.1mm2 vs. 30.2±7.8mm2 [p=0.915]). Disproportionate MR in HFmrEF was also associated with worse 2-year outcome than proportionate MR – 40.1% vs. 16.7% (HR 2.30; 95% CI 1.02–5.17 [p=0.045]. Conclusion This is the first assessment of the effect of disproportionate volume loading secondary to MR in patients presenting in AHF with HFmrEF. Disproportionate MR was associated with worse outcome at 2 years. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Abbott

Myocardial efficiency in severe asymptomatic primary mitral regurgitation: relation to quantitative measures of regurgitation

Abstract Objectives To study the association of myocardial external efficiency (MEE) in mitral regurgitation (MR) towards routinely used quantitative indicators of disease severity and progression. Background Quantitative assessment of LV function and regurgitation in asymptomatic severe primary MR is crucial for management. MEE is a load-independent indicator of mechano-energetic coupling and can be measured non-invasively using 11C-acetate positron emission tomography (PET). The role of MEE in this setting has not been studied. Methods 48 asymptomatic patients with severe primary mitral regurgitation underwent PET, echo, and CMR on the same day. MEE was automatically derived from PET as the ratio of cardiac work (cardiac output * mean arterial pressure) and total left ventricular (LV) oxygen consumption (mean MVO2 * LV mass). LV function and mitral regurgitant volumes (RegVol) were measured by echo and CMR. MEE in MR was compared to healthy volunteers (n=9). MEE and parameters of regurgitation severity and of LV volumes and function were studied as predictors of outcome (valve surgery or death). Results MEE was reduced in MR (21.5±4.2%) vs healthy volunteers (32.0±5.6%, p&amp;lt;0.001) and showed weak but significant correlations (r2&amp;lt;0.25) with regurgitation severity and LV volumes. There were 23 cardiac events (valve surgery: 22; cardiovascular death: 1) during follow-up (median 2.7 years, IQR 1.9–3.2). Univariate Cox models showed that MEE, echocardiographic left atrial volume as well as RegVol and LV ventricular volumes from both echo and CMR were significant outcome predictors (all p&amp;lt;0.05), while LVEF and NT-pro-BNP were not (p&amp;gt;0.05). Prediction by MEE was not affected by age, sex or BMI. When categorically divided by the median MEE was a strong predictor in Kaplan-Meier analysis (log-rank p=0.0004, figure 1) and remained independently significant, compared to all other univariate predictors in bivariate Cox models. Conclusions This study suggests an important role of energetic insufficiency in progression of asymptomatic severe primary MR. Reduced MEE was linked to outcome independently of standard functional measures of regurgitation severity or left ventricular size and function. Strategies for improvement of myocardial energetics in MR are warranted. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish Heart-Lung Foundation Figure 1

Forward Left Ventricular Ejection Fraction as a Predictor of Postoperative Left Ventricular Dysfunction in Patients with Degenerative Mitral Regurgitation.

Background: Left ventricular dysfunction (LVD) can occur immediately after mitral valve repair (MVr) for degenerative mitral regurgitation (DMR) in some patients with normal preoperative left ventricular ejection fraction (LVEF). This study investigated whether forward LVEF, calculated as left ventricular outflow tract stroke volume divided by left ventricular end-diastolic volume, could predict LVD immediately after MVr in patients with DMR and normal LVEF. Methods: Echocardiographic and clinical data were retrospectively evaluated in 234 patients with DMR ≥ moderate and preoperative LVEF ≥ 60%. LVD and non-LVD were defined as LVEF < 50% and ≥50%, respectively, as measured by echocardiography after MVr and before discharge. Results: Of the 234 patients, 52 (22.2%) developed LVD at median three days (interquartile range: 3–4 days). Preoperative forward LVEF in the LVD and non-LVD groups were 24.0% (18.9–29.5%) and 33.2% (26.4–39.4%), respectively (p < 0.001). Receiver operating characteristic (ROC) analyses showed that forward LVEF was predictive of LVD, with an area under the ROC curve of 0.79 (95% confidence interval: 0.73–0.86), and an optimal cut-off was 31.8% (sensitivity: 88.5%, specificity: 58.2%, positive predictive value: 37.7%, and negative predictive value: 94.6%). Preoperative forward LVEF significantly correlated with preoperative mitral regurgitant volume (correlation coefficient [CC] = −0.86, p < 0.001) and regurgitant fraction (CC = −0.98, p < 0.001), but not with preoperative LVEF (CC = 0.112, p = 0.088). Conclusion: Preoperative forward LVEF could be useful in predicting postoperative LVD immediately after MVr in patients with DMR and normal LVEF, with an optimal cut-off of 31.8%.

Long-term clinical and haemodynamic results after transcatheter annuloplasty for secondary mitral regurgitation.

AimsThe study sought to investigate the long‐term outcome after transcatheter mitral valve annuloplasty for secondary mitral regurgitation (MR).Methods and resultsConsecutive patients with symptomatic secondary MR undergoing transcatheter mitral valve annuloplasty with the Carillon device at Leipzig University Hospital between 2012 and 2018 were studied prospectively. Left ventricular (LV) function and MR severity were quantified by standardized echocardiography. 33 patients were included. Mean age was 75 ± 10 years, and 20 patients were women. A Society of Thoracic Surgeons score of 8.1 ± 7.2% indicated high‐risk status. In 24 patients, MR resulted from LV remodelling and dysfunction, eight suffered from left atrial dilatation, and one patient had MR due to combined primary and secondary aetiology. LV ejection fraction at baseline was (median) 38% [inter‐quartile range (IQR) 30–49%]. During the mean follow‐up time of 45 ± 20 months, 17 patients died, two patients withdraw consent, and four patients were lost. Of the remaining patients, four were hospitalized for decompensated heart failure. Two of these patients underwent additional transcatheter edge‐to‐edge mitral valve repair. At follow‐up, New York Heart Association (NYHA) functional class improved from 95% in Class III/IV at baseline to 70% in Class I/II with no patients in NYHA Class IV (P < 0.0001). Mitral regurgitant volume was reduced from 27 mL (IQR 25–42 mL) to 8 mL (IQR 3–17 mL) (P = 0.018) and regurgitant fraction from 42% (IQR 34–54%) to 11% (IQR 8–24%) (P = 0.014). LV end‐diastolic volume index [92 mL/m2 (IQR 74–107 mL/m2) vs. 67 mL/m2 (IQR 46–101 mL/m2), P = 0.065] and end‐systolic volume index [50 mL/m2 (IQR 44–69 mL/m2) vs. 32 mL/m2 (IQR 20–53 mL/m2), P = 0.037] decreased. Total stroke volume remained unchanged [38 mL/m2 (IQR 33–43 mL/m2) vs. 33 mL/m2 (IQR 26–44 mL/m2), P = 0.695], while LV ejection fraction increased [43% (IQR 35–49%) vs. 54% (IQR 46–57%), P = 0.014]. Forward stroke volume, heart rate, and forward cardiac output were not significantly altered.ConclusionsAmong high‐risk patients undergoing transcatheter mitral valve annuloplasty for symptomatic secondary MR, mortality was ~50% at 4 years. In the surviving patients, reduced MR severity was associated with reduced NYHA functional class, reverse LV remodelling, and improved LV function.

Long-term outcome after transcatheter mitral annuloplasty for secondary mitral regurgitation

Abstract Funding Acknowledgements Type of funding sources: None. Background The long-term effects of transcatheter mitral valve annuloplasty (TMVA) for secondary mitral regurgitation is unknown. Purpose We studied the clinical outcome and the effects on left ventricular (LV) function and remodeling and on mitral regurgitation (MR) severity after TMVA using the Carillon annuloplasty device. Methods We analyzed 33 consecutive patients with symptomatic MR who were treated with TMVA at Leipzig University Hospital between 2012 and 2018. Echocardiography was performed before TMVA and at follow-up. MR severity was quantitatively assessed by regurgitant volume (calculated as LV total stroke volume – LV forward stroke volume) and regurgitant fraction (calculated as regurgitant volume / LV total stroke volume). Results Mean age was 80 ± 10 years, 19 patients were women. A Society of Thoracic Surgeons (STS) score of 8.1 ± 7.2% indicated high risk status for mitral valve surgery. In 26 patients, mitral regurgitation resulted from LV remodeling and LV dysfunction, 7 suffered from left atrial dilatation. LV ejection fraction at baseline was 38% (30-49%; median, interquartile range). During a mean follow-up time of 45 ± 20 months, 17 patients died, 2 patients withdraw consent, and 4 patients were lost. Of the remaining patients, 4 were hospitalized for decompensated heart failure, and 2 underwent additional transcatheter edge-to-edge mitral valve repair. At follow-up, NYHA functional class improved from 95% in class III/IV at baseline to 70% in class I/II with no patients in NYHA class IV (p &amp;lt; 0.0001). Mitral regurgitant volume was reduced from 27mL (25-42mL) to 8mL (3-17mL) (p = 0.035) and regurgitant fraction from 43% (32-54%) to 11% (8-24%) (p = 0.020). LV end-diastolic volume index (92mL/m2 (71-107mL/m2) vs. 67mL/m2 (46-101mL/m2), p = 0.084) and end-systolic volumes index (51mL/m2 (44-69mL/m2) vs. 32mL/m2 (20-53mL/m2), p = 0.037) decreased. Thus, total stroke volume remained similar (38mL/m2 (33-43mL/m2) vs. 33mL/m2 (26-44mL/m2), p = 0.695) while LV ejection fraction increased (43% (31-49%) vs. 54% (46-57%), p = 0.032). Forward stroke volume, heart rate and forward cardiac output remained unchanged. Blood pressure was similar at baseline and at follow-up. Conclusion. Among high risk patients undergoing transcatheter mitral valve annuloplasty for symptomatic secondary MR, mortality was about 50% at 4 years. In the surviving patients, reduced MR severity was associated with fewer heart failure symptoms, reverse LV remodeling and improved LV function.