Mitral Regurgitation Research Articles

Interventional treatment of patients with hypertrophic obstructive cardiomyopathy: the immediate and long-term results

Abstract Background Alcohol septal ablation (ASA) is a widely accepted and effective procedure for reducing septal thickness in patients with symptomatic hypertrophic obstructive cardiomyopathy (HOCM) who do not respond to medical treatment and have significant outflow tract gradients. Despite numerous studies confirming its safety and efficacy, as well as current guidelines from 2020 recommending ASA as a class 1 treatment option alongside surgical myectomy[1], the decision between these methods is still a subject of debate. Methods From 2009 to 2022 154 ASA performed in 145 patients (91 males, 54 females) with HOCM at our centre. Mean age of pts. was 42 [6;77] years. All pts. had right ventricle pacing lead with pacemaker backup and myocardial contrast ECHO(MCE) before procedure. Mean peak pressure gradient (PG) on LVOT was 93,5 ± 8,2 mm. Hg. Mitral valve regurgitation (MR) from moderate to severe was in all pts. Mean interventricular septum thickness was 2,5сm [1,6; 3,8]. Results Mean PG on LVOT decreased from 93,5 ± 8,2 mmHg to 31,7±4,3 mmHg. The grade of MR reduced from at least moderate to mild or even trivial. The procedure – related mortality was 1,3%. In 3 cases (2%) the procedure was aborted by he MCE data. Mean follow up for 145pts (100%)was 91±4,6 months. 112(77,3%) pts had PG reduction (to ≤30 mtmHg) – regarded as good result of procedure. 19 (13,1%) pts had PG > 30mmHg, but significant improvement in symptoms. Long term mortality in ASA pts. was 2.7%. 10(6.9%) pts needed redo procedure due to residual LVOTO, which was effective. 13(8,9%) patients had complete AV block and required permanent pacemaker. Mean interventricular wall thickness decreased from 2,5±0,3сm to 1,8±0,2cm. MR decreased from at least moderate to mild or complete disappearance. NYHA class reduced from 2,9 to 1,2. Conclusions ASA is effective and safe method of HOCM treatment. Accumulation of the experience can lead to a reduction in procedure time, a decrease in the number of complications, and an overall improvement in the outcomes of interventional HOCM treatment.

Temporal trends in mitral valve surgery in Denmark: changes in patient characteristics and outcomes from 1996 to 2021

Abstract Background Mitral valve regurgitation (MR) is associated with increased morbidity and mortality. Mitral valve surgery (MVS) is recommended in severe MR, which is the second most common cause of heart valve surgery in the Western world. Data on national practice patterns are lacking and are essential for the continuous epidemiologic surveillance of the disease. Purpose To investigate temporal trends in patient characteristics, incidence and mortality in patients undergoing MVS for MR in Denmark from 1996 to 2021. Methods Using Danish nationwide registries, we identified all patients ≥18 years undergoing MVS for MR. Patients operated due to infective endocarditis were excluded. The study population was grouped into one 6-year and four 5-year calendar bands and type of MVS (mitral valve repair, mechanical or biological valve replacement and transcatheter-edge-to-edge repair (TEER)). Temporal trends in patient characteristics were computed. Annual incidence rates were calculated while considering the total Danish population ≥18 years at risk. For one-year postoperative mortality analysis, the reverse Kaplan-Meier estimator and a multivariable Cox proportional hazard analysis were used. Results We identified 7,813 patients (median age 67.3 years, 65.6% males) undergoing MVS. Over calendar time, burden of comorbidities decreased while median age increased, Table 1. From 1996 to 2021, a stepwise increase was seen in the overall incidence rate for MVS from 3.87 [95% CI 3.32-4.51] to 7.06 [95% CI 6.34-7.58] per 100,000 person-years (p<0.001). The incidence of mechanical valve replacement statistically significantly decreased (p<0.001), while the incidence of mitral valve repair (p=0.004), biological replacement (p≤0.001) and TEER statistically increased (p=0.015), Figure 1. For the overall study period, one-year mortality was 5.0% for mitral valve repair, 12.7% for mechanical valve replacement, 15.7% for biological valve replacement and 19.0% for TEER. Demographics and one-year mortality stratified by calendar period are shown in Table 1. In the mitral valve repair group, adjusted analysis showed a stepwise statistically significant decrease in one-year mortality with HR 0.30 (95% CI 0.17-0.53, p≤0.001) in 2017-2021 as compared to 1996-2001. In the remaining surgical groups, trends were towards decreasing one-year mortality over calendar periods but did not reach statistical significance. Conclusion(s) In this Danish nationwide cohort study, we observed an increase in the incidence of overall mitral valve surgery from 1996 to 2021. The incidence of mechanical valve replacement decreased, while the incidence of mitral valve repair, biological replacement and TEER increased. Mortality rates significantly improved for mitral valve repair patients over calendar time. Continuous epidemiological surveillance of this patient group is required in an era of development in treatment guidelines, surgical methods and patient demographics.Table 1Figure 1

Natural progression of rheumatic aortic valve disease following rheumatic mitral valve intervention: 16-year single center experience

Abstract Backgrounds and Objectives Recognizing the natural progression of the aortic valve (AV) disease is helpful in planning the intervention of significant rheumatic mitral valve (MV) disease accompanying rheumatic AV disease. We aimed to investigate the long-term course of AV disease and the need for AV surgery in patients with rheumatic mitral valve disease who underwent MV intervention. Methods We retrospectively investigated the progression of AV disease with rheumatic changes following MV intervention in a single tertiary center. A total of 890 patients who underwent MV intervention for rheumatic MS or mitral regurgitation (MR) without concurrent AV intervention were initially screened for eligibility. Among them, 76 patients met the criteria for rheumatic etiology and had over a year of echocardiographic follow-up after MV intervention (64 surgery, 12 balloon valvuloplasty). Results The median follow-up period was 4 years (mean 5.8 years, ranging from 1 to 31 years). MS was the most common indication for mitral intervention. Overall, trans-aortic peak velocity (AV Vmax) changed from 2.2 ± 0.6 m/s to 2.4 ± 0.8 m/s, and mean pressure gradient (mean PG) changed from 11.1 ± 6.0 mmHg to 13.2 ± 8.2 mmHg. Six patients fell under severe aortic stenosis (AS) definition-wisely (Figure 1) and three of them were classified as low flow low gradient severe AS despite normal ejection fraction. Eventually, four patients were found to have true-severe AS and only one of them underwent AV surgery for severe AS per se. None of the patients with aortic regurgitation deteriorated to severe (Figure 2). Conclusions Only a small portion of rheumatic AV involvement progresses to severe AS after MV intervention, and performing MV intervention for severe mitral stenosis or mitral regurgitation in patients with concurrent mild or moderate AS or aortic regurgitation due to rheumatic changes might be reasonable.The changes in the grading of ASThe changes in the grading of AR

Prognostic implications of right ventricular dysfunction in degenerative mitral regurgitation

Abstract Background The prevalence and impact of right ventricular dysfunction (RVD) in degenerative mitral regurgitation (DMR) is unknown. We aimed to determine whether RVD assessed by echocardiography in routine clinical practice is independently associated with survival in patients with DMR. Methods We used data from the Mitral Regurgitation International DAtabase-Quantitative (MIDA-Q) which included patients with isolated DMR due to mitral valve prolapse from January 2003 to January 2020 from 5 tertiary centers across North America, Europe, and the Middle East. A cohort of 4,379 (mean age: 67 years, 64.6% males, follow-up:5.3[3.3-8.2]years) consecutive patients with significant (≥moderate) DMR was included and long-term survival was analyzed. Results RVD, identified in 584(13.3%) patients, was associated with reduced 10-year survival (49±3% vs. 67±1%; p<0.001), overall and in all subgroups of patients, even after comprehensive adjustment including left ventricular dilatation and dysfunction, DMR severity, pulmonary pressures and surgery (adjusted HR[95%CI]=1.55[1.31-1.84]; p<0.001). This excess mortality was observed under medical management (adjusted HR[95%CI]=1.39[1.12-1.72]; p=0.003) and after surgical correction of mitral regurgitation (adjusted HR[95%CI]=1.56[1.08-2.27]; p=0.019). Patients with RVD undergoing surgery within 3 months of diagnosis experienced a better 10-year survival (73±4% vs. 38±4%; p<0.001), even after adjustment (adjusted HR[95%CI]=0.53[0.35-0.81]; p=0.003) despite an increase of 1-month post-operative mortality (5% vs 2.2% for patients without RVD; p<0.001). Conclusions RVD is observed in 13.3% of significant DMR and exhibits a powerful and independent association with excess mortality partially attenuated by mitral surgery. Therefore, assessment of right ventricular systolic function should be included in routine DMR evaluation and in the clinical decision-making process.determinant ans prognosis of RVD in MR

Prognostic significance of right ventricle to pulmonary artery coupling acute improvement after mitral transcatheter edge-to-edge repair

Abstract Background Transcatheter Edge-to-Edge Repair (TEER) of mitral valve is a valid treatment option for severe mitral regurgitation. The right ventricle is acutely affected by early hemodynamic changes following the correction of significant mitral regurgitation. Echocardiographic parameters of the right chambers could have a prognostic impact even in a periprocedural setting. In particular, right ventricle to pulmonary artery coupling improvement may be of pivotal importance, as this parameter is a validated marker of right ventricle function. Purpose To evaluate the prognostic impact of early improvement of right ventricle to pulmonary artery coupling assessed by means of the Tricuspid Annular Plane Systolic Excursion/Pulmonary Artery Systolic Pressure (TAPSE/PASP) ratio after TEER. Methods This retrospective single centre study included patients treated with TEER in our hospital from 2015 to 2023. Transthoracic echocardiography was performed before and shortly after device positioning. Acute effects of TEER on echocardiographic parameters were assessed by paired samples t-test. Diagnostic accuracy of the percent variation in the TAPSE/PASP ratio was assessed by means of receiver-operating characteristics analysis. Prognosis was evaluated by Kaplan-Meier analysis. Results The study included 95 patients (age 78 ± 10 years; 63% men; BMI 25 ± 5 kg/m2) with severe or moderate-to-severe mitral regurgitation. Mean baseline Left Ventricle (LV) ejection fraction was 45 ± 16%, LV end-diastolic volume was 157 ± 62 ml and effective regurgitant orifice area was 41 ± 25 mm2. Post-procedural echocardiographic assessment showed early improvement of LV end-diastolic diameter (p < 0.001), LV end-diastolic volume (p = 0.025), LV stroke volume (p < 0.001), LV global longitudinal strain (p < 0.001), right ventricle free wall longitudinal strain (p < 0.001) and PASP (p = 0.002). Percent improvement of TAPSE/PASP ratio showed a sufficient diagnostic accuracy in predicting a composite outcome of hospitalisation for heart failure and all cause mortality at 1 year (area under the curve 0.66, p = 0.047), with an optimal cut-off of 5.5%. An improvement of the TAPSE/PASP ratio over this threshold was associated with a reduction in the composite outcome (hazard ratio 0.38, p = 0.045). Conclusion TEER improves both left and right ventricular dynamics, which can be detected with echocardiography. In particular, an acute improvement of the TAPSE/PASP ratio is associated with an improvement in short-term prognosis. A comprehensive assessment of right ventricular function, including TAPSE/PASP ratio, should be routinely performed before and after TEER.

Elevated mitral valve pressure gradient following transcatheter edge-to-edge repair is independently associated with inferior outcomes in atrial, but not in ventricular secondary mitral regurgitation

Abstract Background In transcatheter mitral valve edge-to-edge repair (M-TEER), the goal of optimizing post-procedural residual mitral regurgitation inadvertently carries the risk of generating relevant mitral stenosis, resulting in an elevated mean mitral valve pressure gradient (MPG). In patients with primary mitral regurgitation, an elevated post-procedural MPG has been found to independently predict impaired outcomes. However, the effect of elevated post-procedural MPG on outcome after M-TEER in patients with secondary mitral regurgitation (SMR) has yet to be fully elucidated. This study investigated the impact of elevated MPG on outcome in the EuroSMR registry, a large, multi-center real-world cohort of patients with SMR. Methods This retrospective study included patients who underwent M-TEER for SMR between 2009 and 2021 in 12 centers. Patients were stratified into two groups based on SMR etiology: (1) ventricular SMR (vSMR), and (2) atrial SMR (aSMR). The etiology was considered as vSMR in patients with a left ventricular ejection fraction (LV-EF) <50% and aSMR in subjects with preserved left ventricular function (LV-EF ≥50%) and a markedly dilated left atrium (Left Atrial Volume Index [LAVi] ≥40ml/m2). According to the proposed M-VARC threshold, post-procedural MPG was assessed by discharge transthoracic echocardiography and was considered elevated if >5 mmHg. The primary endpoint was all-cause mortality after 5 years, with statistical analysis conducted using Kaplan-Meier and uni- and multivariable Cox Regression analysis. Results Among the 1703 patients in the study (vSMR: n=1420; aSMR: n=283), elevated post-procedural MPG was observed in 9.4% (n=133) of vSMR and 19.1% (n=54) of aSMR patients. Atrial fibrillation was significantly more prevalent in aSMR (78.4% vs. 57.1%, p<0.001). Patients with vSMR had a higher median surgical risk assessed by the EuroScore II (aSMR vs. vSMR: 7.0% [IQR 4.0, 13.1] vs. 4.9% [IQR 2.9, 8.5], p<0.001). Kaplan-Meier analyses for all-cause mortality after 5 years demonstrated significant differences in aSMR patients (low vs. elevated MPG: 48.9% vs. 69.8%, log-rank p<0.01), while there was no difference in vSMR patients (55.7% vs. 60.8%, log-rank p=0.66) (Figure 1). This observed effect remained significant even after accounting for common confounding factors: elevated MPG was an independent predictor for all-cause mortality in aSMR patients (HR=1.86; 95%-CI: 1.14-3.02, p=0.013) but not in vSMR patients (HR=1.00; 95%-CI: 0.74-1.35, p=0.99). Conclusion Our findings suggest that elevated post-procedural MPG is an independent predictor of adverse outcomes in patients with aSMR, but not in those with vSMR. This effect may partially be explained by a reduced left atrial function and higher rates of atrial fibrillation.Figure 1.Study flowchart

The prognostic impact of tricuspid regurgitation improvement after left-sided valvular interventions

Abstract Background Tricuspid regurgitation is a common bystander in patients with left-sided valvular heart disease such as mitral regurgitation (MR) or aortic stenosis (AS). Data on the prognostic impact of potential TR improvement after interventions for left sided valvar disease is scarce. Objectives This study aimed to assess incidence and prognostic value of TR improvement after left-sided valvular interventions (M-TEER and TAVI) using merged data from two prospective single-center registries. Methods The merged database included all consecutive patients with symptomatic left-sided valvular heart disease (MR or AS) undergoing either M-TEER or TAVI from 2008 until 2023. The prognostic impact of baseline TR severity and TR improvement was assessed using Kaplan-Meier estimates and stepwise Cox regression. TR improvement was defined as a reduction in TR severity at discharge by at least one grade compared to baseline in patients with ≥moderate TR at baseline. Results A total of 4,461 patients undergoing left-sided valvular interventions (M-TEER: N=663; TAVI: N=3,798) were eligible for study inclusion (age 81.0 years [IQR 76.2-84.7], 52.7% male). TR severity at baseline was none or mild in 70.9% (N=3,161), moderate in 19.4% (N=864), and severe in 9.8% (N=436). Patients with ≥moderate TR at baseline showed significantly higher rates of all-cause mortality (p<0.001) and of the combined endpoint after 3 years (p<0.001), compared to patients with none or mild TR. This finding was consistent for the M-TEER and TAVI subgroups. Among patients with ≥moderate TR at baseline (N=1,300), 499 patients (38.4%) showed TR improvement by at least one grade following left-sided valvular intervention, while TR did not improve in 801 patients (61.6%). In the overall study population, patients with TR improvement showed lower rates of all-cause mortality (p<0.001) and the combined endpoint after 3 years (p=0.006) (Figure 1A, 1B). This finding was consistent only in the subgroup of patients undergoing M-TEER (p=0.013 and p=0.003), but not for patients undergoing TAVI (p=0.12 and 0.62) (Figure 2A, 2B). Following stepwise Cox regression (incl. adjustment for treatment), TR ≥moderate at baseline was independently associated with death (p=0.0019) and combined death or HF rehospitalization (p=0.0068) 3 years after intervention (Figure 3A,3B). TR improvement was independently associated with survival (p=0.015) and combined survival or absent HF rehospitalization (p=0.032) 3 years after intervention (Figure 4A, 4B). Conclusions Patients with TR improvement after left sided valvular interventions showed significantly better clinical outcomes compared to those without. These results reinforce the need for assessment for TR assessment before and after left-sided valvular interventions and may identify patients that qualify for subsequent TR intervention.

Prognostic stratification of patients with mitral regurgitation using artificial intelligence-enhanced electrocardiogram for left ventricular diastolic function assessment

Abstract Background The determination of left ventricular diastolic dysfunction (LVDD) and filling pressure in patients with significant (>moderate) mitral regurgitation (MR) poses a complex challenge. We recently validated an artificial intelligence-enabled electrocardiogram (AI-ECG) algorithm to detect LVDD and estimate LV filling pressures. Methods This retrospective study sought to examine the risk of all-cause mortality across AI-ECG LVDD grades. Patients from the AI-ECG LVDD study test cohort who underwent transthoracic echocardiography confirming significant MR and an ECG within fourteen days of each other at Mayo Clinic between 09/2001 and 06/2022 were included. LVDD status was determined based on the index ECG, and patients were categorized into groups representing normal diastolic function (NDF) or LVDD grades 1 (G1), 2 (G2), or 3 (G3). Results Of 4,019 patients with significant MR (mean age 69.8, 49.0% women), 1,175 (29.2%), 1,881 (46.8%), and 963 (24.0%) were classified by AI-ECG as NDF/G1-LVDD, G2-LVDD, and G3-LVDD, respectively. The median mitral effective regurgitant orifice area was 26 mm² (interquartile range 20-36 mm²). Over a median follow-up of 3.5 years, 1,636 (40.7%) patients died. In multivariable survival analysis adjusted for multiple risk factors, a worse AI-ECG LVDD grade was independently associated with an increased death risk [G2DD: adjusted hazard ratio (aHR) 1.98 (95% confidence interval (95% CI) 1.63-2.40), G3DD: aHR 2.59 (95% CI 2.09-3.20)]. These findings were consistent when accounting for mitral valve intervention and among patients with >moderate MR or after mitral valve intervention. Conclusion In patients with significant MR, the grading of LVDD by AI-ECG is independently associated with all-cause mortality.

Echocardiographic evaluation of cardiac remodelling in a cohort of patients with heart failure and reduced ejection fraction treated with dapagliflozin

Abstract Background Several mechanisms have been proposed to explain SGLT2 inhibitors’ (SGLT2i) beneficial effects in patients with heart failure (HF), but their exact mode of action in this setting is not fully understood. Pivotal randomised clinical trials regarding this class of drugs in HF setting have not reported echocardiographic data regarding potential cardiac positive remodelling. Objectives To assess the effects of dapagliflozin treatment initiation on cardiac remodelling in patients with HF and reduced ejection fraction (HFrEF), with a focus on left ventricular performance and atrial volumetry. Methods In this retrospective observational study, we analysed data from 94 patients with HFrEF in whom dapagliflozin had been prescribed as part of HF treatment optimization. Inclusion criteria were: age > 18 years; ongoing optimal medical therapy (OMT) for HF according to 2021 ESC HF guidelines (except for SGLT2i); transthoracic echocardiogram within 30 days of baseline assessment demonstrating a left ventricular (LV) ejection fraction (EF) <40%; comprehensive assessment at 6 months with clinical, laboratory and echocardiographic data. Results Patients (mean age 71.7 ± 9.8, 76% males, coronary artery disease as HFrEF main aetiology in 66%) showed significant cardiac remodelling after dapagliflozin initiation, specifically in terms of stroke volume index (SVi, +9.7 ml/m2, p<0.001), LVEF (+5.1%, p<0.001), LV end-diastolic volume (LV EDV) index (-8.4 ml/m2, p<0.001), left atrial (LA) volume index (-3.9 ml/m2, p=0.026), and LV mass index (LVMi, -12.9 gr/m2, p=0.004). BNP tended to significantly decrease (-168.6 ng/L, p=0.025). Percentage of patients with an indication for ICD implantation in primary prevention went from 36.2% to 8.5%, p<0.001. We did not observe significant differences in terms of mitral regurgitation (MR) grading at follow-up (in particular, the proportion of patients with severe MR remained approximately stable: 7% vs 4%, p=0.86). We did not observe any change in diastolic function measured by E/e’ ratio (mean difference -0.6; 95% CI -2.2 to 0.9, p=0.41). Conclusions Treatment with dapagliflozin resulted in positive remodelling in our cohort of patients with HFrEF in terms of chamber volumes, contractility parameters (and this was not explained by an improvement in MR severity) and LVMi. There was a significant decrease in natriuretic peptide as well as in the proportion of patients with primary prevention ICD indication. Our findings highlight the need of further data to fully elucidate the exact mechanism that leads to LA and LV positive remodelling with SGLT2i.Figure 1.Change in TTE Parameters

Left ventricular end-systolic and diastolic elastance as predictors of cardiac events in patients who underwent mitral valve surgery for severe mitral regurgitation

Abstract Background/Introduction In severe mitral regurgitation (MR), the prognostic significance of left ventricular ejection fraction (LVEF) and LV dimensions is well-established. However, the assessment of diastolic function in this patient presents a notable challenge, and its impact on postoperative outcomes remains unclear. Purpose This study was designed to explore the potential of LV end-systolic (Ees) and diastolic elastance (Eed) as novel predictors for cardiac events following surgery. Methods A retrospective cohort study was performed on 199 patients (53% male, average age 60 years, mean LVEF 60.0%) with severe MR and undergoing surgery. Preoperative Ees and Eed were calculated using established formulas: Ees = (systolic blood pressure x 0.9) / LV end-systolic volume, and Eed = left atrial pressure / stroke volume, with left atrial pressure estimated from mitral Doppler flow parameters as SBP – (4 x peak MR velocity²). The primary outcome was defined as either cardiac death or hospitalization due to heart failure. Results Average values for Ees and Eed were 2.61 (IQR: 1.67-3.20) and 0.32 (IQR: 0.05-0.57), respectively. Univariate analysis indicated Ees (HR: 1.24, 95% CI: 0.99-1.57, p = 0.066) and Eed (HR: 5.93, 95% CI: 2.87-12.26) as potential predictors. Adjusting for age, LVEF, and LV dimensions, Eed remained an independent predictor of cardiac events (HR: 5.89, 95% CI: 2.81-12.28). Stratifying Eed at a threshold of 0.31—identified as best sum of sensitivity and specificity—revealed that Eed > 0.31 were associated with a 3.9-fold increase in cardiac events compared to those with Eed ≤ 0.31 (p = 0.008). (Fig.) Conclusions The assessment of Eed is a straightforward and readily available parameter in routine clinical practice. Our findings advocate for the inclusion of preoperative Eed evaluation as an independent prognostic indicator for patients undergoing surgery for severe MR.Event free survival by Eed

Identification of left ventricular flow features in healthy and pathological conditions

Abstract Background In the presence of mitral valve diseases or following surgical interventions, the hemodynamics in the left ventricle (LV) are significantly altered [1]. These maladaptive intraventricular hemodynamic alterations can stimulate a cascade of events leading to progressive adverse LV remodeling and eventual heart failure [2]. Qualitative and quantitative evaluation of LV flow features may provide a potential for sensitive risk stratification of clinical cardiac function [3]. Purpose The purpose of this study is to identifying LV flow features using in vitro experiments under both normal and pathological conditions, including mitral regurgitation (MR), mitral valve replacement with bioprosthetic/mechanical valve, and transcatheter mitral valve edge-to-edge repair (TEER). Methods We utilized a biohybrid approach to construct the in vitro experimental platform, where the native mitral valve (including chordae tendineae and papillary muscles) and aortic valve from porcine were combined with a 3D-printed silicon LV (figure 1). To ensure comparability across different conditions, we maintained consistency by utilizing the same native valve and 3D-printed LV. For pathological conditions, we cut the chordae tendineae in A2 zone to induce the severe degenerative MR, and TEER was performed on this prolapsed valve by placing two clips in A2-P2 zone. Then, the anterior leaflet of valve was cut, and a bioprosthetic valve and mechanical valve were sutured to mitral annulus to simulate surgical valve replacement, respectively. Left ventricular flow fields were measured using four-dimensional particle image velocimetry (4D-PIV) technique, with vector interval of 0.9 mm in all the spatial directions and temporal resolution of 10 ms. Results Significant differences in mean flow field were observed among healthy and pathological conditions (figure 2). Firstly, the vortex orientation was clockwise in healthy, MR, bioprosthetic valve replacement, and TEER conditions, which could accompany the redirection of blood flows towards the aortic valve. However, the replacement with a mechanical valve resulted in an alteration in vortex orientation from clockwise to counterclockwise. Secondly, the position of the center of the vortex changed in pathological conditions, with the center of the vortex closest to the apex and the left ventricle outflow tract in the healthy condition. Thirdly, the maximum Reynolds shear stress (RSS), which may be responsible for thrombus formation, significantly increased after TEER procedure and bioprosthetic valve replacement. Conclusions This study demonstrates significant changes in LV hemodynamics across different conditions. The flow features, including vortex orientations, vortex positions and the RSS, may potentially become crucial considerations for the optimization of artificial valves and mitral valve repair devices.Figure 1 Figure 2

Trans catheter edge to edge repair for mitral regurgitation and left ventricular outflow obstruction in hypertrophic cardiomyopathy

Abstract Background Based on previous reports, mitral valve transcatheter edge to edge repair (TEER) may be considered in patients with severe mitral regurgitation (MR) and left ventricular obstruction in patients with hypertrophic obstructive cardiomyopathy (HOCM) that are high risk for surgery. Objective We aimed to evaluate the feasibility, and immediate and short-term outcomes of mitral TEER in symptomatic patients with severe MR and HOCM. Methods Five patients (age 75±6, 3 men) with severe MR and HOCM with high surgical risk, and anatomy not suitable for septal ethanol ablation, who remained symptomatic despite maximally tolerated drug therapy were selected for TEER using the MitrClip system. Result The procedure was performed successfully on all 5 patients. Devices were deployed at the A2-P2 scallops of the mitral valve. MR severity declined from severe to mild in all patients, left ventricular outflow (LVOT) maximal gradient decreased from 140±46 to 8±5 mmHg after TEER, and was 41±32 mmHg at 4±2 month follow- up, Clinically, all patients reported improvement of their symptoms to Class I-II NYHA functional Class. Conclusion TEER may be a beneficial procedure for severely symptomatic patients with severe MR and obstructive HOCM on maximal tolerated medical therapy, who are not amenable to surgery because of excessive risk, old age, and frailty.Pre and Post procedure EchoPre and Post Cath

The prognostic impact of intra-procedural mitral valve gradient following transcatheter edge-to-edge repair for primary mitral regurgitation

Abstract Background/Introduction The impact of intra-procedural mitral valve gradient following transcatheter edge-to-edge repair (TEER) in primary mitral regurgitation (MR) is a matter of controversial debates. Purpose The aim of this study was to investigate the prognostic impact of intra-procedural mean mitral valve gradient (MPG) in patients with primary MR undergoing TEER. Methods The PRIME-MR registry included consecutive patients with primary MR undergoing TEER from 2008-2022 at 27 international sites. Clinical outcomes were assessed according to intra-procedural mean MPG measured at the end of the procedure by transesophageal echocardiography. The evolution of mean MPG from intra-procedural to discharge and follow-up was documented. Baseline characteristics and clinical outcomes of patients were investigated according to intra-procedural mean MPG using a cut-off of 5mmHg (low MPG: ≤5mmHg, high MPG: >5mmHg). The prognostic impact of intra-procedural mean MPG was evaluated in multivariable Cox regression analysis. The primary endpoint was 2-year all-cause mortality or heart failure (HF) hospitalization. Results Intra-procedural MPG was available in 1,516 patients (median age 82 years [IQR 76.0, 86.0], 55.1% male). Patients with high intra-procedural MPG presented with less atrial fibrillation and less severe MR but were more symptomatic at baseline than patients with low MPG. Moreover, patients with high intra-procedural MPG had higher baseline MPG and smaller LV dimensions (LVEDV and LVESV). The rate of patients with mean MPG >5mmHg increased from intra-procedural (18.3%) to discharge (31.3%), while remaining stable thereafter (1-year follow-up: 30.9%; last follow-up: 29.6%). At 1-year follow-up the rate of patients presenting with New York Heart Association (NYHA) functional class I or II did not differ between patients with low (82.3%) and high MPG (83.6%, p=0.93). Kaplan-Meier analysis according to mean MPG showed no difference between patients with low and high MPG for the primary endpoint (32.4% vs. 42.1%, p=0.12), as well as for the single endpoints of all-cause mortality (22.3% vs. 27.7%, p=0.47) and HF hospitalization (17.6% vs. 27.5%, p=0.087) through 2 years (Figure 1). Unadjusted spline analyses were provided to depict the prognostic impact of continuous intra-procedural MPG (Figure 2). Following multivariable Cox regression neither MPG >5mmHg (HR 0.91, 95%-CI 0.56-1.49, p=0.72), nor continuous MPG (HR 1.05, 95% CI 0.96-1.15, p=0.28) were independently associated with adverse clinical outcomes. Conclusions Based on a large international cohort of patients with primary MR undergoing TEER, intra-procedural mean MPG did not significantly affect clinical and functional outcomes at 2 years. The long-term impact of elevated post-procedural MPG warrants further investigation.Figure 1Figure 2

Mitral valve reoperation versus first-time surgery for mitral regurgitation: comparison of patient characteristics, type of surgery and mortality in a nationwide cohort

Abstract Background Mitral valve reoperation has been estimated to carry higher surgical risk than first-time mitral surgery. Contemporary data on this area is needed as these associations may lead to under-treatment of recurrent mitral valve disease requiring intervention. Purpose To compare patient characteristics, type of surgery, and early mortality related to mitral valve reoperation versus first-time surgery for mitral regurgitation in a nationwide setting. Methods We identified patients ≥18 years undergoing first-time surgery for mitral regurgitation 1996-2021 using Danish nationwide registries. Patients undergoing first-time surgery due to endocarditis were excluded. The study population was categorized into 1) patients who underwent first-time surgery only; 2) patients who underwent mitral reoperation. The first group was followed from date of first-time surgery, while second group was followed from date of reoperation, and baseline characteristics were defined according to their respective index dates. Mortality was examined during 180-day follow-up using the reverse Kaplan-Meier estimator and multivariate Cox analysis was used to compare mortality rates within 30 days and 180 days of follow-up. Subgroup analysis was conducted after excluding patients undergoing reoperation for infectious endocarditis (IE). Results We identified 7,470 patients; 7,058 (94.5%) underwent first-time surgery only and 412 (5.5%) underwent mitral reoperation. Compared to patients who only underwent first-time surgery, reoperated patients were younger (median age 60 vs. 67) and had fewer comorbidities at time of reoperation, Table 1. Prosthetic replacement was performed in 35.6% of first-time surgeries and 77.2% of reoperations. Mortality after 30 days was 5.2% after first-time surgery and 3.2% after reoperation, while 180-day mortality were 7.8% and 10.6%, respectively, Figure 1. Compared to first-time surgery, reoperation was associated with no significant difference in 30-day mortality (HR=0.68, 95%CI 0.39-1.19), but an increased rate of 180-day mortality (HR=1.60, 95%CI 1.17-2.19, p=0.003). After excluding patients with IE in the reoperation group (n=57), mortality was 2.8% and 8.8% after 30 and 180 days, respectively. In this subgroup, compared to first-time surgery, the 30-day rate of mortality was HR=0.61 (95%CI 0.32-1.14) and after 180 days HR=1.34 (95%CI 0.93-1.93, p=0.11). Conclusion Compared to patients who only underwent first-time mitral surgery, patients undergoing mitral reoperation were younger and had fewer comorbidities at time of reoperation. Repair was favoured for first-time surgery, while prosthetic replacement was favoured for reoperations. Compared to first-time surgery, reoperation was associated with an increased risk of 180-day mortality. Though patients undergoing reoperation for mitral valve disease are carefully selected, our findings suggest that this procedure should still be considered at high risk of an adverse outcome.Table 1Figure 1

Left atrial strain differences between hypertensive and sarcomeric left ventricular hypertrophy: a sign of sarcomeric auricular myopathy?

Abstract Introduction In clinical practice, left ventricular (LV) hypertrophy is a common finding that can be caused by physiologic or pathologic conditions. An etiologic diagnosis is extremely important because it may change the prognosis and management of the patient and his family. Left atrial (LA) dysfunction is common due to diastolic dysfunction but, in patients with sarcomeric LV hypertrophy, primary cardiomyopathy disease could also be present. Purpose To evaluate if there are differences in LA function between arterial hypertension (HT) and hypertrophic cardiomyopathy (HCM) patients. Methods 73 patients with HCM (according to ESC guidelines criteria) and 82 patients with HT (under treatment with ≥1 hypertensive drug for ≥3 months) and ≥13mm of LV hypertrophy underwent an echocardiography to assess LA function with strain analysis and LV diastolic function. Continuous normally distributed variables were compared with T-student test and categoric variables with square-chi or exact Fisher test if required, accepting as significant a p-value <0.05. Results Globally, HCM patients showed thicker LV walls and larger LA indexed volumes (18.7±4.7 vs. 13.3±0,8 mm and 44.9±20.7 vs. 30.7±8.8 ml/m2, p<0.000 for both). Also, HCM patients presented diastolic dysfunction and atrial fibrillation history in a higher frequency (31 vs. 7.6% and 16.4% vs. 0%, p<0.000 for both). LA strain was significantly lower in HCM patients as compared to the HT group (LA contractile 11.5±5.8 vs. 17.2±4.4, p<0.000; LA conduit 12.2±5.4 vs. 13.3±3.8, p=0.041; and LA reservoir 23.9±8.7 vs. 31.1±5.9, p<0.000). In the subgroup of patients with moderate-severe LV hypertrophy (<17mm) and no significant mitral regurgitation (n=103; HCM=21, HT=82), LA contractile strain remained lower in HCM as compared to HT patients (13.2±4.8% vs. 17.2±4.4%, p<0.000) (figure 1); without differences in diastolic dysfunction, LA volumes, significant mitral regurgitation or atrial fibrillation history. Conclusions Our results show that LA strain is more impaired in HCM patients as compared to HT patients. Specifically, contractile LA strain remained lower even in those patients with moderate-severe LV hypertrophy, despite having similar LV diastolic function, LA indexed volumes, significant mitral regurgitation, or atrial fibrillation history. These findings could be caused by HCM involvement of the LA myocytes. In the context of moderate-severe hypertrophy of unknown origin with non-significant mitral regurgitation, the detection of abnormally reduced LA strain could indicate the presence of an HCM.Figure 1

Risk assessment using DEVI and CARPREG -1 score to predict maternal adverse cardiac cvents in pregnancies with valvular heart disease: external validation study from MPAC registry

Abstract Background Even though many risk assessment tools in pregnant women with valvular heart disease (VHD) are available, validation studies are few that assess their performance in diverse settings, which is needed prior to the application of routine clinical practice. Objectives To validate and establish the clinical utility of two risk stratification tools – DEVI (VHD-specific tool) and CARPREG-I in predicting adverse cardiac events in pregnant patients with VHD. Methods This cohort study involved consecutive pregnancies complicated with VHD enrolled in the prospective MPAC registry from July 2016 to December 2019(1). The ability to discriminate those with and without adverse cardiac outcomes was assessed using the area under the curve for both the DEVI and CARPREG-1 scores. Performance was assessed through discrimination and calibration characteristics. Clinical utility was evaluated with Decision Curve Analysis. Results Among 1029 pregnancies complicated with heart disease in the MPAC registry cohort, 604(52.3%) with valvular heart disease were included in this analysis. One or more composite adverse cardiac events occurred in 70 (11.6%) pregnancies during antenatal or the early postpartum period. Mitral regurgitation was the most common lesion (67.7%). In assessing the pregnancy outcomes, those who continued past 20 weeks were included, with the majority (92.0%) delivered at term, and the cesarean rates were 33.6% (n=203). The most common adverse event was heart failure (n=32, 5.3%), most of which (68.6%) occurred in the postnatal period. There were 11 maternal deaths (1.8%) during the study period, six among those with mechanical heart valves (four prosthetic valve thrombosis), two among those with severe mitral stenosis and pulmonary hypertension and two with severe mitral regurgitation and infective endocarditis. The area under the receiver operating characteristic curve (AUC) was 0.766, with 95% confidence intervals (CI) 0.703- 0.828 for DEVI and 0.703 (95%CI 0.644- 0.763) for CARPREG-I models. Calibration plots suggested that the DEVI score overestimates risk at higher probabilities, whereas the CARPREG-I score underestimates the risk at most probabilities. Decision curve analysis demonstrated that both models were useful across predicted probability thresholds between 10% and 60%. Conclusion In this external validation study in pregnant women with primary rheumatic VHD, DEVI and CARPREG-I scores showed good discrimination ability and clinical utility across various probabilities. Both can be used to classify those who develop adverse cardiac outcomes during pregnancy and childbirth. However, both models need recalibration to improve the agreement between the predicted and observed events prior to routine application in diverse clinical settings.Figure 1.a and b ROC and Decision Curves

Calculation of intraprocedural hemodynamics with computational functional dynamic in mitral valve edge-to-edge repair

Abstract Background Hemodynamic outcomes in patients undergoing transcatheter edge-to-edge-repair of the mitral valve (M-TEER) are difficult to predict. Computational functional dynamic (CFD) is frequently used in biomedical engineering to simulate blood flow patterns under various conditions. The authors developed a standardized workflow for individualized analyses and investigated the hemodynamic of mitral regurgitation volumes and gradients by using CFD. Methods 20 patients from two high volume centers who suffered from severe mitral regurgitation (MR) and underwent full cycle cardiac computed tomography (CT) prior procedure were enrolled. Baseline computed tomography and intraprocedural data were analyzed. Based on the specific valve morphology, individualized CFD-simulations were performed to calculate MR volumes prior to intervention and estimate hemodynamics after M-TEER. Results CFD-analyses of 20 patients (mean age 80±4 years, 60% male) showed excellent correlation between baseline PISA method-based MR volumes (45±23ml) measured in transesophageal echocardiography (TEE) and CFD-based calculation (45±26ml; R=0.917; P<0.001) as well as between TEE-measured mean baseline effective regurgitant orifice area (EROA; 27±16mm²) and CFD-measured EROA (24±18mm²; R=0.869; P<0.001)). After device implantation, correlation between intraprocedural TEE-measured and CFD-estimated correlation for residual MR volumes (R=0.949; P<0.001) and EROA (R=0.841; P<0.001) remained robust. Post-interventional mean diastolic pressure gradient (TEE) was 3.6±2.8mmHg which was in close correlation with the CFD estimated gradient (3.0±1.8mmHg, R=0.905; P<0.001). Conclusions This is the first study to use a CFD-standardized workflow for predicting hemodynamic changes in patients undergoing M-TEER using data from two different centers. In the future, CFD-based analyses might serve as a key-diagnostic tool for predicting residual MR volumes and gradients for M-TEER-procedures.Comparison of TEE and CFD flow patternBland-Altman-Blots

Intra, short and long-term results of mitral VIV for the degenerated surgical mitral prosthesis from italian VIV registry (MIVIV registry)

Abstract Background/Introduction Reoperation of failed bioprosthetic mitral valves is associated with significant morbidity and mortality. Transcatheter mitral valve-in-valve (MViV) replacement was explored early in the development of THVs with transseptal/transfemoral (TS/TF) and transapical (TA) approaches. Purpose This is the first Italian Registry on mitral VIV and it was designed to explore contemporary MViV outcomes with all types of balloon expandable valves. The present study out of the registry aims to asses the >10 years follow-up outcomes in terms of mortality, gender diversity, and perioperative result. Methods Participating centers used standardized definitions to collect clinical information, including patient demographic characteristics, comorbidities, functional status, quality of life indexes, procedural details, and patient outcomes from consecutive MViV cases. Cohort of 265 patients was available for the primary analysis and follow-up too.The patients were grouped by 11 hospitals in Italy performing VIV for degenerated biological mitral prostheses. Results A total of 265 pts underwent mitral VIV due to bioprosthesis degeneration between January 2010 and January 2023. They have been subdivided by transfemoral (TF) with 117 (44%) pts and transapical (TA) with 148 (55,8%) pts. Most of the patients were of female sex (59,2%) and EuroScore II for surgical re-operation was 16.1%. Mixed disease (48%) was more common than mitral regurgitation (29%) and stenosis (22%). 69,8% of the total cohort was in class NYHA III and the mean LVEF was 54%.Otherwise, there were no significant demographic differences between patients undergoing TS and TA. In TF there was more severe PVL (5%)(p-value: 0,001) and much more cases of severe grade of stenosis (54,7%) and regurgitation (57%)(p-value< 0,0001). Considering intraoperative outcomes, technical success has been established in around 97,7% of the total cohort without difference btw groups. Only 3,3% died during hospitalization without difference between groups (P-value=0,735). LVOT obstruction has been seen in 3,4% in the case of TA and 0 for TF. Only 1,5% of the total cohort underwent surgical conversion as well as embolization in only 1,1%. Overall survival from the total cohort was 91,3% at >10 years, Figure 1. Concerning the freedom from cardiac death (CV death) was 96,6% in the total cohort at 13 years. Concerning the difference between access, the general survival is established at 97,4% in TF while 86,3% in TA (p-value =0,050)(Figure 2). Freedom from CV death was 99,1% in TF and 94,5 in TA (p-value=0,209). In gender analysis differentiation, the general survival in females was 98,5% in TF and 85,6% in TA at 13 years (p-value=0,056). Conclusion(s) Transcatheter MViV using a balloon-expandable valve is associated with high technical success, a low complication rate, and a solid long-term benefit in terms of survival. Transseptal access was associated with lower mortality compared with TA access.Figure 1Figure 2

Prevalence, characteristics, and long-term outcomes of patients with mitral annular disjunction undergoing surgery for degenerative mitral regurgitation

Abstract Background Mitral valve prolapse (MVP) is associated with progressive mitral regurgitation (MR) requiring surgical repair. A subset of patients with MVP may also suffer from malignant ventricular arrhythmias (VAs), especially in the presence of mitral annular disjunction (MAD). Purpose To assess the prevalence, associated characteristics, and long-term outcomes of patients with MVP with and without MAD undergoing mitral valve surgery for degenerative MR. Methods Patients with MVP and moderate-to-severe or severe degenerative MR undergoing mitral valve surgery between 2010-2022 at a university hospital in Sweden were included. MAD length was measured on echocardiograms at end-systole from the insertion of the posterior leaflet on the detached mitral annulus to the border of the bulging left ventricle. Patient demographics and clinical outcomes were collected from medical records. The primary endpoint consisted of VAs, defined as sustained- or non-sustained ventricular tachycardia or high burden of premature ventricular complexes causing hospitalizations or ablation or identified at Holter monitoring. Other endpoints included sudden cardiac death, all-cause mortality, new onset postoperative atrial fibrillation, stroke, mitral valve reoperation, endocarditis, new or worsened heart failure, myocardial infarction and implantation of permanent pacemaker or cardiac defibrillator. Results Of 599 patients undergoing mitral valve surgery, 96 (16%) had preoperative MAD, with a median (Q1, Q3) MAD length of 8.0 (5.0-10.0) mm. Compared with patients without MAD, patients with MAD were younger (55 vs 63 years), more likely to be female (31% vs 17%), to have diffuse myxomatous valve disease (66% vs 25%) and bileaflet prolapse (57% vs 17%). Most patients underwent mitral valve repair (84% vs 80%). No patient had residual MAD after surgical repair. At a mean follow up time of 5.8 ± 3.5 years after mitral valve repair, VAs were more common in patients with pre-operative MAD (10% vs 2% (adjusted HR 4.52, 95% CI 1.57-13.0)) (Figure 1). There were no significant differences in the risks of other clinical outcomes. Conclusions MAD was associated with almost a 5-fold increased long-term risk of VAs after mitral valve repair despite successful anatomical correction of MAD. These findings highlight the importance of increased awareness of VAs in patients with MAD also after mitral valve surgery.

Insulin-like growth factor binding protein 2 predicts course of concomitant right-ventricular dilation and tricuspid regurgitation after transcatheter edge-to-edge mitral valve repair

Abstract Aims Right ventricular (RV) dilation and secondary tricuspid regurgitation (TR) are highly prevalent comorbidities in patients with mitral regurgitation and are associated with a worse prognosis. TR improvement after successful transcatheter edge-to-edge mitral valve repair (M-TEER) is reported regularly, however specific factors contributing to the recovery of RV function and TR after M-TEER are poorly understood. Particularly the role of serum biomarkers in this context is unclear. We aimed to identify specific biomarkers associated with the course of concomitant RV dilation and TR after M-TEER. Methods and Results We prospectively included 242 patients undergoing M-TEER at our center and obtained pre-procedural blood samples for biomarker analysis. A commercial multiplex protein assay (Cardiovascular III, Olink, Uppsala, Sweden) was used to quantify expression levels of 92 defined biomarkers. We then analyzed differences in biomarker expression between patients with and without right ventricular reverse remodeling (RVRR) as defined by improvement of concomitant TR by at least one grade and/or downsizing of the basal RV diameter of at least 10%. 242 patients were included in this analysis, 94 had no/mild concomitant TR at baseline, 148 had moderate/severe TR. RV diameters correlated with TR severity and were significantly larger in patients with moderate/severe TR. At baseline, expression of numerous cardiometabolic biomarkers was significantly higher in patients with moderate/severe TR. These included NT-proBNP (1.9-fold, p < 0.001), matrix metalloproteinase 2 (1.4-fold, p < 0.001) as well as insulin-like growth factor binding proteins 1 (1.7-fold, p < 0.001), -2 (1.3-fold, p = 0.001) and -7 (1.4-fold, p < 0.001). Follow-up analysis was performed in patients with initial moderate/severe TR. The course of TR and RV dimensions three months after M-TEER could be assessed in 99 patients (56 with moderate TR, 43 with severe TR). RVRR had occurred in 50 patients (50.5%). Patients without RVRR had a higher prevalence of chronic pulmonary disease (24.5 vs. 2.2%, p < 0.001). No further differences in clinical characteristics were found. Specifically, RV diameter, systolic pulmonary artery pressure (sPAP) and right-ventricular systolic function did not differ substantially between both groups. Strikingly however, the expression of insulin-like growth factor binding protein 2 (IGFBP-2) was significantly higher in patients, who did not develop RVRR (fold change 1.3 compared to patients with RVRR, p = 0.022). After adjustment for covariates IGFBP-2 was independently associated with absence of RVRR (Odds Ratio 2.078, 95% Confidence interval 1.108 – 3.897, p = 0.023). Conclusions In patients undergoing M-TEER with concomitant moderate or severe TR, numerous cardiometabolic biomarkers including IGFBP-2 are upregulated. Higher levels of IGFBP-2 at baseline are independently associated with persistent TR and/or RV dilation after M-TEER.