Secondary Mitral Regurgitation Research Articles

Contemporary review of the evolution of various treatment modalities for mitral regurgitation.

Mitral regurgitation is one of the commonest valvular heart diseases for which there have been several innovative treatment strategies that have developed over the last several decades. We describe the various treatment modalities that have been used for the last several decades. All articles in PubMed, Cochran and Embase were screened from inception to August 2024 for the following - 'Mitral valve regurgitation' 'Mitral valve repair' 'Mitral valve replacement' 'Robotic mitral surgery' 'Transcatheter mitral valve repair.' Mitral regurgitation (MR) is classified into primary and secondary MR. Causes of primary MR include degenerative disease, rheumatic heart disease, and infective endocarditis. Secondary MR is observed in the setting of left ventricle (LV) pathology, including ischemic or dilated cardiomyopathy. In secondary MR, annular dilation, papillary muscle displacement, tethering of chordae tendineae and/or mitral valve (MV) leaflets result in leaflet restriction and malcoaptation. In this review, we discuss various modalities for treatment of mitral regurgitation, as well as newer treatment options for MR including robotic MV repair and other minimally invasive procedures. Several ongoing randomized controlled trials in this topic will help shed more light and provide guidance to deliver the optimal care for our patients.

Abstract 4117438: Machine Learning Predicts Successful Transcatheter Mitral Valve Edge to Edge Repair: A Systematic Review and Meta-Analysis

Introduction: Transcatheter Mitral Valve Edge to Edge Repair (TEER) is an established percutaneous treatment for patients with severe symptomatic Mitral Regurgitation (MR). The current AHA/ACC guidelines recommend TEER for inoperable patients with severe primary MR or patients with symptomatic severe secondary MR despite medical therapy. Machine learning (ML) has emerged as a tool for TEER risk stratification due to the paucity of established risk scores. To address the lack of consensus on its efficacy, we conducted a systematic review and meta-analysis of studies that utilized ML to predict the success of TEER. Methods: Electronic databases, including Embase, MEDLINE, and the Cochrane Library, were searched from inception through April 2024. We included studies that used TEER and employed at least one ML model to predict the success of TEER. The Area Under the Receiver Operating Characteristic Curve (AUC) was used to measure the accuracy of ML risk stratification algorithms. Results: 102 publications were screened, with seven eventually included in this analysis. Two studies employed clustering techniques, two utilized extreme gradient boosting, and three used multiple ML algorithms to predict outcomes. Of the four studies that compared the accuracy of ML with traditional Cox regression, all four demonstrated higher accuracy with ML, and this difference was statistically significant in three of the four studies. The mean AUC of the aggregated ML data was 0.737 [95% CI: 0.717, 0.758], compared to 0.627 [95% CI: 0.600, 0.653] for the pooled traditional methods. Conclusions: To our knowledge, we conducted the first systematic review and meta-analysis of ML methods for prediction of TEER success. ML outperformed established risk scores, demonstrating promising potential. Future ML models, trained on larger patient datasets, may further improve predictive accuracy in this patient population.

Biological plausibility and implications of obesity associated valvular heart diseases

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

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

Prognostic value of left atrial and ventricular strain in moderate atrial and ventricular secondary mitral regurgitation

Abstract Background Secondary mitral regurgitation (SMR) is associated with increased morbidity and mortality. In these patients, left ventricular global longitudinal strain (LVGLS) and left atrial reservoir strain (LARS) have been proposed to improve risk stratification. However their prognostic value was shown to be inconsistent when considering the SMR etiology (i.e. atrial or ventricular), possibly due to be the influence of atrial fibrillation (AF) on these measures and specifically LARS. Moreover, data focusing on moderate SMR is lacking. Aim To investigate the prognostic value of LVGLS and LARS in patients with SMR stratified according to etiology, and to identify optimal threshold for both measures. Methods Patients (n=1061; age 68±11years , 59% male) with moderate SMR were retrospectively included and classified as ASMR or VSMR, and further subdivided into "sinus rhythm (SR) subgroup" (ASMR-SR: n=68 , VSMR-SR: n=435) or as "AF subgroup" (ASMR-AF: n=284 , VSMR-AF: n=274), if patients had history of AF. The endpoint was a composite of heart failure events and all-cause mortality. Threshold values for LVGLS and LARS were defined based on spline curve analysis. Results As compared to VSMR, ASMR patients were more frequently female (61% vs. 35%, p<0.001), had less comorbidities and were less symptomatic (i.e. NYHA functional class III-IV in 11% of ASMR vs. 24% of VSMR, p<0.001). For the echocardiographic characteristics, VSMR patients showed lower LV ejection fraction and LVGLS, as compared to ASMR patients. For both ASMR and VSMR, patients in the AF subgroups had larger LA volume index, lower LARS and more severe tricuspid regurgitation (Figure 1). During a median follow-up of 78 (IQR: 44-111) months, 27% of ASMR-SR, 37% of ASMR-AF, 50% of VSMR-SR and 72% of VSMR-AF group reached the combined endpoint. Separated multivariable cox regression analyses were performed in ASMR and VSMR patients (Table 1): for both etiologies, LARS and LVGLS were independently associated with the endpoint after correcting for other significant variables at the univariate analysis, including the SR or AF group and the interventions during follow-up. In addition, a stepwise addition of LVGLS and LARS to a basic model led to a significant difference in the likelihood ratio for both groups. The thresholds of LVGLS and LARS associated with an increased risk of the combined endpoint differed per etiology. For LVGLS the threshold was <16% for ASMR, and <12% for VSMR. When considering LARS assessment, different thresholds were identified according to the SR or AF group: <18% in ASMR-SR; <15% in ASMR-AF; <17% in VFMR-SR and <12% in VFMR-AF. Conclusion In moderate SMR patients, LVGLS and LARS are independently associated with outcomes both in ASMR and VSMR and could be considered to improve risk stratification. However, lower threshold for both parameters should be considered based on etiology and on the presence of AF.

Prognosis in patients with residual pulmonary hypertension after transcatheter edge-to-edge repair for secondary mitral regurgitation

Abstract Background Pulmonary hypertension (PH) is an independent prognostic predictor in patients with heart failure (HF). Recently, transcatheter edge-to-edge repair (TEER) for secondary mitral regurgitation (MR) has been reported to reduce HF hospitalizations and mortality. Elevated pulmonary artery pressure (PAP) before TEER is associated with a poor prognosis; however, the impact of residual PH after TEER on clinical events has not been investigated. Purpose The purpose of this study is to clarify whether residual PH influences outcomes in patients with HF treated by TEER for secondary MR. Methods We included 63 patients who underwent TEER for severe secondary MR and post-procedural right heart catheterization in our institute from January 2016 to August 2023. Mean PAP after TEER was categorized as increased (>20mmHg) versus not increased (≤20mmHg), and we investigated the clinical outcomes between the two groups. The primary endpoint is a composite outcome of all-cause mortality and HF hospitalization. Results Among 63 patients, the average age was 78 years, and 60.3% were male. All patients had Secondary MR, and 52 patients (82.6%) had ventricular Secondary MR—right heart catheterization after TEER revealed a mean PAP of 21.6±7.7 mmHg, pulmonary vascular resistance (PVR) of 2.7±1.4 wood unit (WU), and pulmonary artery wedge pressure (PAWP) of 12.2±5.9 mmHg. Patients with residual PH had higher composite outcome rates of death from any cause or HF hospitalization compared to those without PH (56.1% vs. 19.5%; hazard ratio: 2.62; 95% confidence interval: 1.1 to 6.9; p=0.03). Multivariate Cox regression analysis showed that residual PH and higher PAWP after TEER were associated with higher mortality (hazard ratio: 1.14; 95% confidence interval: 1.03 to 1.28; p=0.01). Conclusion Our results suggest that patients with residual PH after TEER have a poor prognosis. Residual PH and high PAWP after TEER are associated with mortality.

Prognostic impact of mitral valve geometry in patients with secondary mitral regurgitation: a secondary analysis of the MITRA-FR trial

Abstract Background Mitral valve (MV) transcatheter edge-to-edge repair (TEER) has emerged as a second line therapy on top of guidelines-directed medical treatment (GDMT) in heart failure (HF) patients with severe secondary mitral regurgitation (SMR). Following the disparate results of the COAPT and MITRA-FR pivotal trials, echocardiographic markers of LV remodeling and MR severity have been proposed to select patients most likely to benefit from MV-TEER. The characterization of MV geometry arises as a potential tool to stratify risk of outcomes in SMR patients, who underwent classical surgery or MV-TEER intervention. However, it remains unknown whether MV geometry parameters were associated with prognosis in MITRA-FR patients and whether MV-TEER could modulate their impact on outcomes. Purpose To evaluate the association between MV geometry and outcomes of HF patients with SMR in the MITRA-FR trial, as well as the impact of SMR treatment modality. Methods Thirteen MV geometry parameters were assessed from baseline transthoracic echocardiograms in patients from the MITRA-FR trial. The prognostic impact of MV geometry parameters was studied on top of the baseline clinical variables used in the primary analysis of MITRA-FR (i.e. age, atrial fibrillation [AF], ischemic cardiomyopathy, myocardial infarction, left ventricular ejection fraction [LVEF] and effective regurgitant orifice area [EROA]). The primary endpoint was the composite of all-cause mortality or HF hospitalization (HFH) within 2 years. The effect of treatment arms (MV-TEER plus GDMT vs. GDMT alone) on this association was also evaluated. Results Among the 307 patients included in the pivotal trial, 272 were analyzed in the present study (i.e. 135 from the GDMT group and 137 from the GDMT + MV-TEER group). Mean age was 70±10, 74% male. 50% had ischemic cardiomyopathy and 34% AF. LVEF was 33±7% and EROA was 31±11 mm². MV geometry parameters were presented for the whole population and according to the randomization group in the Table. Among these parameters, only MV tenting area remained independently associated with the primary endpoint (Hazard Ratio (HR) = 1.22 per 1 cm², Confidence Interval (CI) = 1.01-1.47; p=0.041) after multivariate analysis (Figure). Tenting height was independently associated with the risk of HFH (HR=1.07 per 1 mm, CI=1.00-1.14, p=0.037), but no MV geometry variable was associated with all-cause death. These findings remained consistent in both treatment arms (p>0.20 for interaction). Conclusion In HF patients with SMR included in the MITRA-FR trial, MV tenting area and MV tenting height were independently associated with the risk of HFH or all-cause mortality and HFH respectively, without any difference according to treatment arms. These data suggest that MV tethering provides an incremental prognostic value beyond classical echocardiographic variables, including EROA, and then should be considered in the risk stratification of patients with HF and SMR.Table of MV geometry parameters featuresMultivariate analysis (Forrest-plots)

Comprehensive stress echocardiography uncovers the heterogenity of phenotypes in non-ischemic heart failure with abnormal ejection fraction

Abstract Background Heart failure (HF) with abnormal left ventricular (LV) ejection fraction (EF) manifests in multiple phenotypes, each presenting distinct and potentially actionable therapeutic targets. This study aimed to assess the potential of the ABCDE+ stress echocardiography (SE) protocol in uncovering different phenotypes of non-ischemic HF. Methods With a retrospective analysis of prospectively acquired data, we identified 265 patients (mean age: 65.7±12.6 years; 154 males, 59.9%) with non-ischemic HF with EF<50% (mean =41.4±7.5) enrolled by 23 certified laboratories between 2021 and 2023. Ischemic origin was excluded based on data of angiography and medical history. ABCDE-SE was evaluated with exercise (n=98, 37.0%), dobutamine (n=50, 18.9%), or vasodilators (n=117, 44.1%). The protocol consisted of several steps: A assessed regional wall motion abnormality (RWMA); B evaluated number of B-lines; C measured left ventricular contractile reserve; Step D with coronary flow velocity reserve (CFVR) in the left anterior descending artery (LAD) was completed in 102 patients (38.5%); step E assessed heart rate reserve. Additionally, step F (evaluated in 188 patients at rest and 107 at peak stress) noted the presence of rest or stress-induced moderate-to-severe secondary mitral regurgitation. The SE response was graded on a scale from 0 (all steps normal) to 5 (all ABCDE+ steps abnormal). Results The mean ABCDE score was 1.5±1.2, ranging from 0 (n=59, 22.3%) to 5 (n=2, 0.8%) (see distribution of scores in Figure 1A). Abnormal results were observed in 21 subjects (7.9%) for A, 86 (32.5 %) for B, 147 (55.5%) for C, 42/102 (41.2%) for D, and 101 (38.1%) for E steps. Step F was abnormal in 22/188 (11.8%) at rest and in 16/107 (14.9%) at peak stress. The predominant "solitary phenotypes" (only one step abnormal) were impaired LV contractile function phenotype (step C in 47, 51.1%) followed by chronotropic insufficiency (step E in 17, 18.5%) and congestive phenotype (step B in 17, 18.5%) (see Figure 1B). The most frequent combined phenotype was BCE – congestive phenotype with impaired ventricular and heart rate reserves (28 [62.2%]). Notably, 38 patients (14.3%) demonstrated improved regional contractility, while 27 patients (10.2%) showed new regional wall motion abnormality (see Table). Conclusion Non-ischemic HF patients with abnormal EF exhibit a broad spectrum of phenotypes. Impaired left ventricular contractility, interstitial congestion, and chronotropic insufficiency are the most frequent abnormalities detected by ABCDE-SE. Up to one-quarter of such patients demonstrate normal SE results. This comprehensive approach paves the way for personalized, SE-guided therapy.

The effect of exercise on RV-PC coupling in asymptomatic patients with significant primary mitral regurgitation

Abstract Background Right ventricular–pulmonary circulation (RV-PC coupling) serves as an index to evaluate RV function in relation to underlying RV afterload. Although impaired RV-PC coupling has been proposed as a predictor of adverse outcomes in heart failure (HF) patients with secondary mitral regurgitation (MR), there is limited data available for patients with primary MR. Purpose The objective of this study was to assess and compare alterations in RV-PC coupling during exercise with bicycle stress echocardiography in individuals with asymptomatic moderate to severe primary MR (MR group) and normal subjects (Control group). Μethods All patients and controls underwent stress echocardiography with a supine bicycle. RV systolic function was evaluated with TAPSE and S’. The non-invasively measured RV-PC coupling was evaluated by indexing TAPSE and S’ to right ventricular systolic pressure (RVSP) during baseline echocardiogram and peak workload stages of bicycle SE. Results Among the 48 patients in the MR group (mean age 53.5±15.16 years, 58.3% female), 39 patients had moderate MR(81.3%), 5 patients had moderate-to-severe MR(10.4%), and 4 patients had severe MR(8.3%). The duration of stress echocardiogram was significantly shorter in the MR group compared to control group (8.11±2.39 min vs 10.5±1.05 min, respectively; p<.001). Left Ventricular Ejection Fraction (LVEF) was within normal limits in both groups {70.7±11.9 % vs 72.6±12.1 %(p=NS} and the dimensions of left ventricular cavity (end-diastolic and end-systolic diameters) were significantly larger in the MR group compared to control group (49.25±5.21 mm vs 45.6±4.08mm (p .016) and 31.81±4.27mm vs 29.07±4.21mm (p .033) respectively}. TAPSE and RVSP increased from baseline to peak dose [23.48 ±3.05mm vs 29.94±3.48mm (p < .001), 8.54±4.56mmHg vs 43.79±5.27mmHg (p < .001), respectively]. There were no significant differences in TAPSE/RVSP and S’/RVSP between the two groups at rest. However, a significantly steady decrease was observed from baseline to peak dose (0.84±0.16 mm/mmHg vs 0.72±0.19mm/mmHg (p <.001) and 0.52±0.11 cm/sec/mmHg vs 0.50±0.15 cm/sec/mmHg (p .004), respectively). Conversely, these parameters did not exhibit a significant decrease in the control group. Finally, there was no significant correlation observed between the changes in the index TAPSE/RVSP , ratio E/E’ and systolic blood pressure. Conclusions RV-PC coupling decreases during exercise in asymptomatic patients with moderate to severe MR, independently of left ventricular dynamic changes. In contrast , there is no significant change in RV-PC coupling observed in the control group. Therefore, future studies should aim to evaluate the incremental role of this novel index not only in the assessment and evaluation of patients with MR but also as a potential prognostic marker.TAPSE/RVSP GraphTable of echocardiographic measurements

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

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

Giant Left Atrium in an Infant with Anomalous Origin of Left Coronary Artery from Pulmonary Artery

AbstractAnomalous origin of the left coronary artery (ALCAPA) from the pulmonary artery is a rare congenital anomaly with coronary steal and myocardial ischemia. The left ventricular dilatation leads to mitral regurgitation causing left atrial enlargement. We report a rare case of giant left atrium in an infant with ALCAPA-mediated secondary mitral regurgitation, which has been hitherto unreported.

Comparing surgical techniques and results of secondary ischemic mitral regurgitation: a state-of-the-art literature review.

Surgery for mitral valve disease is a developing area with a wide range of surgical options. There is growing evidence on the best approach for secondary ischemic mitral regurgitation (SIMR) when the pathology is within the ventricle. The goal of this literature review is to provide a comprehensive comparison of surgical treatments for SIMR. The initial screening process included PubMed, Medline and Embase to identify randomized controlled trials, propensity-matched observational series, meta-analyses and unmatched observational series. The terms used were 'mitral valve disease', 'secondary mitral regurgitation', 'secondary ischemic mitral regurgitation', 'functional mitral regurgitation', 'restrictive mitral annuloplasty', 'subvalvular repair', 'Trans Catheter Edge to Edge Repair and echocardiography coupled with secondary mitral regurgitation', 'secondary ischemic mitral regurgitation', and 'functional mitral regurgitation'. Six strategies have been identified for treating SIMR. These include mitral valve replacement (MVR), restrictive mitral annuloplasty, surgical revascularisation (with and without mitral annuloplasty), subvalvular procedures [papillary muscle (PM) approximation, PM relocation, ring and string procedure], procedures directly targeting the mitral valve (edge-to-edge repair and anterior leaflet enlargement), and transcatheter heart valve therapy. There is a deficiency of robust empirical data to enable meaningful comparisons between MVR, mitral valve repair (including subvalvular repair), and transcatheter mitral valve procedure. This review will definitively analyze the current outcomes of transcatheter mitral valve procedure using the edge-to-edge mitral valve repair technique and standard surgical mitral valve procedures in patients with secondary mitral regurgitation (MR). In addition, the seminar highlights the role of left ventricular assist devices in managing SIMR. It discusses the advantages and limitations of each intervention. Currently, there is no consensus on the optimal management strategy for patients with SIMR. Therefore, a multidisciplinary cardiac team should manage patients with secondary MR to ensure the best outcome by matching the ideal intervention with the patient.

Best treatment option for secondary mitral regurgitation surgery: a network meta-analysis of randomized and non-randomized controlled studies

The objective of this study is to ascertain whether subvalvular papillary muscle repair in conjunction with restrictive mitral valve annuloplasty represents the most efficacious treatment for patients presenting with secondary ischemic mitral regurgitation, as compared to restrictive mitral valve annuloplasty alone and to mitral valve replacement. A network meta-analysis was conducted to investigate outcomes of randomized controlled trials, propensity-matched studies, and observational studies, comparing various treatments for secondary ischemic mitral regurgitation. The average follow-up duration for late mortality was 4.4 years. Coronary artery bypass grafting (CABG) without mitral valve surgery had a late mortality incidence of 3.7%. Restrictive mitral annuloplasty demonstrated a rate of 6.5%, while restrictive mitral annuloplasty + CABG resulted in a rate of 4.1%. Subvalvular papillary muscle repair plus restrictive mitral annuloplasty ± CABG and mitral valve replacement + CABG had rates of 4.4% and 5.1%. SUCRA analysis showed that CABG was the most effective treatment for reducing late mortality (70.0%). This was followed by subvalvular papillary muscle repair plus restrictive mitral annuloplasty with or without CABG (62.4%). The top strategy for decreasing early death, reoperation, and readmission to the hospital for heart failure is subvalvular papillary muscle repair plus restrictive mitral annuloplasty with or without CABG, based on SUCRA probabilities (84.6%, 85.54%, and 86.3%, respectively). Subvalvular papillary muscle repair plus restrictive mitral annuloplasty ± CABG has potential to reduce the risks associated with early mortality, reoperation, and re-hospitalization for heart failure. However, further research is required to substantiate these findings.

Weekly Journal Scan: is MATTERHORN a game changer for secondary mitral regurgitation? Still climbing.

Weekly Journal Scan: is MATTERHORN a game changer for secondary mitral regurgitation? Still climbing.

Clinical and echocardiographic parameters associated with outcomes in patients with moderate secondary mitral regurgitation

BackgroundSignificant secondary mitral regurgitation (SMR) is known to be associated with worse prognosis. However, data focusing specifically on moderate SMR and associated risk factors are lacking. In the present study,...

Secondary mitral regurgitation surgical management: a narrative review.

The most common valvular heart disease in the US is moderate to severe mitral regurgitation (MR). Function MR or secondary MR comprises many of these cases. Moderate and severe secondary MR are independently associated with increased all-cause mortality and rehospitalization for heart failure. Both ischemic and nonischemic cardiomyopathy can cause secondary MR via similar pathophysiology that leads to inadequate valve leaflets coaptation. The management of secondary MR is complex. The optimal treatment strategy for secondary MR remains controversial, reflected in the vast array of treatment options and the complexity of therapeutic decision-making. Several surgical mitral valve repair techniques have been described in the literature. Many of these aims to facilitate adequate valve leaflet coaptation. In this review, the pathophysiology of MR is described with a focus on evaluating and managing secondary MR. A literature review was performed using PubMed and Google Scholar. Clinical trials, meta-analyses, randomized controlled trials, reviews, and systematic reviews were considered from January 1, 1995 through December 31, 2022. Articles published in languages other than English with limited text availability were excluded. Optimal therapeutic approach in severe secondary MR is complex and several patient factor should be considered. We provide a framework for the surgical management of secondary MR based on echocardiographic parameters, the presence of ischemia, and myocardial viability. Further study is needed to guide the selection of patients most likely to benefit from mitral valve repair or replacement in the setting of secondary MR.

Prediction of Cardiovascular Events and Structural and Functional Remodeling of the Heart in Patients With Severe Mitral Regurgitation of Various Genesis Underwent Transcatheter Mitral Valve Repair "Edge-To-Edge".

To search for predictors of adverse cardiovascular events after edge-to-edge transcatheter mitral valve repair (TMVR) in patients with severe mitral regurgitation (MR) of various origins with an assessment of structural and functional remodeling of the heart and left ventricular (LV) contractile function. The study included 73 patients (median age 71 [63; 80] years, 60.3% men) at a high surgical risk with severe MR of primary and secondary genesis, who underwent TMVR. The second-generation (58.9%) and fourth-generation (41.1%) clips were implanted. In addition to standard echocardiographic (EchoCG) indices, the parameters of left heart chamber longitudinal strain and LV myocardial function were assessed at baseline, on days 4-5, and at 6 and 12 months after the intervention. Also, the N-terminal fragment of the pro-brain natriuretic peptide (NT-proBNP) was assessed at baseline and on days 4-5 after TMVR. A significant decrease in MR was achieved during 12 months of follow-up. In the group with primary mitral regurgitation (PMR), MR decreased from 4.0 [3.4; 4.0] to 2.0 [1.5; 2.5] at one year of follow-up (p<0.001). In the group with secondary mitral regurgitation (SMR), MR decreased from 3.5 [3.0; 3.9] to 2.0 [2.0; 2.5] at 12 months of follow-up (p<0.001). This effect was associated with volumetric unloading of the left heart chambers evident as a significant decrease in the volumetric indices of the left chambers and an increase in the cardiac index. In the early postoperative period, the LV function was impaired as shown by decreases in the ejection fraction (EF), global longitudinal strain (GLS), LV myocardial function parameters, and an associated increase in NT-proBNP. By 12 months of follow-up, statistically significant improvements in global constructive work (GCW) and global work index (GWI) relative to baseline values were noted in both groups without significant changes in EF and LV GLS. A strong correlation was found between LV EF and GCW (r=0.812, p<0.001) and GWI (r=0.749, p<0.001). The overall survival was 89%, not differing between groups (p=0.72); the absence of hospitalization for decompensated heart failure (HF) was 79.5%, also without significant differences between the groups (p=0.78). According to multivariate regression analysis, the baseline GCW value was the strongest predictor of rehospitalization for decompensated HF (relative risk (RR) 0.997; 95% confidence interval (CI) 0.995-1.000; p=0.021) and the composite endpoint (CEP) (hospitalization for decompensated HF + all-cause mortality) (RR 0.998; 95% CI 0.996-1.000; p=0.033) in the cohort with PMR. In the group with SMR, the initial degree of MR was related with rehospitalization and the CEP (OR 12.252; 95% CI 2.125-70.651; p=0.005 and OR 16.098; 95% CI 2.944-88.044; p=0.001, respectively). The most significant predictor of overall mortality in the study population was the preoperative value of LV stroke volume (OR 0.824; 95% CI 0.750-0.906; p<0.001). Edge-to-edge TMVR exerts a positive effect on the prognosis and structural and functional remodeling of the heart in patients with PMR and SMR. Myocardial function indices may be useful in assessing the LV contractile function in patients with severe MR of various origins. Identification of predictors for adverse cardiovascular events, including with new EchoCG technologies, may contribute to better patient stratification.

Atrial fibrillation in combination with severe mitral regurgitation : Which should be treated first, the atrial fibrillation or the mitral valve?

The primary therapeutic approach for severe secondary mitral regurgitation (MR) in combination with atrial fibrillation is often not clear. To create atherapeutic guideline for daily clinical practice based on acase report as well as basic literature. If afunctional component is suspected, restoration of sinus rhythm may lead to asignificant improvement in MR. The extent of the improvement and the time required to achieve this improvement are often difficult to predict. The involvement of an electrophysiologist is recommended in order to assess the likelihood of successful long-term rhythm control aimed at improving MR. In unclear cases, cardioversion combined with short-term administration of antiarrhythmic medication may be useful to demonstrate potential improvement of MR in sinus rhythm.

Impact of beta-blocker uptitration on patients after transcatheter edge-to-edge mitral valve repair for secondary mitral regurgitation: The OCEAN-mitral registry

BackgroundOptimal medical therapy for patients with secondary mitral regurgitation (SMR) undergoing transcatheter edge-to-edge mitral valve repair (M-TEER) remains unclear. This study aimed to investigate the association between beta-blocker uptitration and clinical outcomes after M-TEER. MethodsUsing data from the Japanese multicenter registry, we examined 1474 patients who underwent M-TEER for SMR between April 2018 and June 2021. Beta-blocker uptitration was defined as an increased dose of beta-blockers 1 month after M-TEER compared with that before M-TEER. The 2-year clinical outcomes were compared between patients with and without beta-blocker uptitration, utilizing multivariable Cox regression analyses and propensity score matching (PSM). ResultsOf the 1474 patients who underwent M-TEER, 272 (18.4 %) were receiving increasing doses of beta-blockers at the 1-month follow-up. These patients had lower left ventricular ejection fraction (LVEF) and higher B-type natriuretic peptide levels. Most patients in the beta-blocker uptitration group received less than the target dose of beta-blockers. Multivariable Cox regression analyses showed that beta-blocker uptitration was significantly associated with a lower risk of all-cause (adjusted hazard ratio [HR]: 0.55; 95 % confidence interval [CI]: 0.36–0.84; P = 0.006) and cardiovascular mortalities (adjusted HR: 0.45, 95 % CI: 0.26–0.79, P = 0.006). PSM analyses revealed consistent findings. Subgroup analyses revealed a significant interaction between beta-blocker uptitration and LVEF≤40 % (interaction P = 0.018). ConclusionsIn patients with SMR, beta-blocker uptitration after M-TEER was associated with better clinical outcomes, especially in the group with an LVEF≤40 %. Efforts to uptitrate guideline-directed medical therapy after M-TEER for SMR may be necessary, even if reaching the target dose proves challenging.

Metabolic gene therapy in a canine with pulmonary hypertension secondary to degenerative mitral valve disease.

Myxomatous mitral valve disease (MMVD) stands out as the most prevalent acquired canine heart disease. Its occurrence can reach up to 40% in small breed dogs and escalates in geriatric canine populations. MMVD leads to thickening and incomplete coaptation of valve leaflets during systole, resulting in secondary mitral valve regurgitation. Serious complications may arise concurrently with the worsening of mitral valve regurgitation, including left-and right-sided congestive heart failure, and pulmonary hypertension (PH). Ultimately, the PH progression might contribute to the patient's demise or to the owner's decision of euthanasia. Most currently available FDA-approved therapies for PH are costly and aim to address the imbalance between vasoconstriction and vasodilation to restore endothelial cell function. However, none of these medications impact the molecular dysfunction of cells or impede the advancement of pulmonary vascular and right ventricular remodeling. Recent evidence has showcased successful gene therapy approaches in laboratory animal models of PH. In this manuscript, we summarize the latest advancements in gene therapy for the treatment of PH in animals. The manuscript incorporates original data showcasing sample presentations, along with non-invasive hemodynamic assessments. Our findings demonstrate that the use of metabolic gene therapy, combining synthetic adeno-associated virus with acid ceramidase, has the potential to significantly reduce the need for drug treatment and improve spontaneously occurring PH in dogs.