Project description:Ischaemic mitral regurgitation (IMR), a frequent complication following myocardial infarction (MI), leads to higher mortality and poor clinical prognosis if untreated. Accumulating evidence suggests that mitral valve (MV) leaflets actively remodel post MI, and this remodelling increases both the severity of IMR and the occurrence of MV repair failures. However, the mechanisms of extracellular matrix maintenance and modulation by MV interstitial cells (MVICs) and their impact on MV leaflet tissue integrity and repair failure remain largely unknown. Herein, we sought to elucidate the multiscale behaviour of IMR-induced MV remodelling using an established ovine model. Leaflet tissue at eight weeks post MI exhibited significant permanent plastic radial deformation, eliminating mechanical anisotropy, accompanied by altered leaflet composition. Interestingly, no changes in effective collagen fibre modulus were observed, with MVICs slightly rounder, at eight weeks post MI. RNA sequencing indicated that YAP-induced genes were elevated at four weeks post MI, indicating elevated mechanotransduction. Genes related to extracellular matrix organization were downregulated at four weeks post MI when IMR occurred. Transcriptomic changes returned to baseline by eight weeks post MI. This multiscale study suggests that IMR induces plastic deformation of the MV with no functional damage to the collagen fibres, providing crucial information for computational simulations of the MV in IMR.
Project description:AimRandomized controlled trials comparing the use of the MitraClip device in addition to guideline directed medical therapy (GDMT) to GDMT alone in patients with secondary mitral regurgitation (MR) have shown conflicting results. However, if these differences could be due to the underlying MR aetiology is still unknown. Therefore, we aimed to evaluate if the effects of percutaneous edge-to-edge repair with MitraClip implantation could differ in patients with ischaemic (I-MR) and non-ischaemic mitral regurgitation (NI-MR).Methods and resultsPubMed, Embase, BioMed Central, and the Cochrane Central Register of Controlled Trials were searched for all studies including patients with secondary MR treated with the MitraClip device. Data were pooled using a random-effects model. Primary endpoint was the composite of all-cause death and heart failure-related hospitalization. Secondary endpoints were the single components of the primary endpoint, New York Heart Association functional Classes III and IV, and mitral valve re-intervention. Seven studies enrolling 2501 patients were included. Patients with I-MR compared with patients with NI-MR had a similar risk of the primary endpoint (odds ratio: 1.17; 95% confidence interval: 0.93 to 1.46; I2 : 0%). The risk of all-cause death was increased in patients with I-MR (odds ratio: 1.31; 95% confidence interval: 1.07 to 1.62; I2 : 0%), while no differences were observed between the two groups in terms of the other secondary endpoints.ConclusionsThe risk of mortality after MitraClip implantation is lower in patients with NI-MR than in those with I-MR. No absolute differences in the risk of heart failure related hospitalization were observed between groups.
Project description:The management of mitral regurgitation (MR) is challenging - patients may be asymptomatic, oligosymptomatic, older with comorbidities, or clinically symptomatic and not appropriate for surgery. The current review assesses morbidity, mortality, and risk factors associated with functional and organic MR, with a focus on severe MR.A structured literature review was conducted in MEDLINE, Embase, the Cochrane Library, and via hand-searching of conference proceedings. Prospective randomised controlled trials and observational studies including adult patients with MR reporting on treatment response rates, survival, time-to-treatment failure, quality of life, and adverse events were eligible for inclusion.In total, 32 publications met the inclusion criteria (9 in functional, 18 in organic, and 5 in functional/organic). Despite study heterogeneity, an increased risk of mortality and morbidity was observed which increased with MR severity. Risk factors associated with mortality and morbidity included advancing age, presence of atrial fibrillation, increasing effective regurgitant orifice, ejection fraction, left ventricle end systolic diameter, diabetes, and increasing New York Heart Association class.The current review represents one of the most comprehensive conducted in the medical/conservative management of MR. An increased risk of mortality and morbidity, which appeared to rise with greater severity, was associated with MR (versus no MR). An unmet need exists in the management of patients with severe symptomatic MR and a high surgical risk as they have a poor prognosis and limited treatment options. Further research into alternative medical strategies and patient management is needed to improve prognoses and reduce mortality and morbidity.
Project description:Background and objectiveThe 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.MethodsA 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.Key content and findingsOptimal 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.ConclusionsFurther 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.
Project description:Secondary mitral regurgitation (MR) refers to MR resulting from left ventricular or left atrial remodeling. In ischemic or nonischemic cardiomyopathy, left ventricular dilation (regional or global) leads to papillary muscle displacement, tethering, and leaflet malcoaptation. In atrial functional MR, MR occurs in patients with left atrial dilation and altered mitral annular geometry due to atrial fibrillation. In addition to cardiac remodeling, leaflet remodeling is increasingly recognized. Mitral leaflet tissue actively adapts through leaflet growth to ensure adequate coaptation. Leaflets, however, can also undergo maladaptive thickening and fibrosis, leading to increased stiffness. The balance of cardiac and leaflet remodeling is a key determinant in the development of secondary MR. Clinical management starts with detection, severity grading, and identification of the underlying mechanism, which relies heavily on echocardiography. Treatment of secondary MR consists of guideline-directed medical therapy, surgical repair or replacement, and transcatheter edge-to-edge repair. Based on a better understanding of pathophysiology, novel percutaneous mitral repair and replacement devices have been developed and clinical trials are underway.
Project description:Mitral regurgitation (MR) represents the second most frequent valvular heart disease. The appropriate management of organic MR remains unclear in many aspects, especially in several specific clinical scenarios. This review aims to discuss the current guideline recommendations regarding the management of organic MR, while highlighting the controversial aspects encountered in daily clinical practice. The role of imaging is essential in establishing the most appropriate type of surgical treatment (repair or replace), which is based on morphological mitral valve (MV) characteristics (reparability of the valve) and local surgical expertise in valve repair. The potential advantages of 3-dimensional echocardiography in assessing the MV are discussed. Other modern imaging techniques (tissue Doppler and speckle tracking) may provide additional useful information in borderline cases. Exercise echocardiography (evaluating MR severity, pulmonary pressure, or right ventricular function) may have an important role in the management of difficult cases. Finally, the moment when surgery is no longer an option and alternative solutions should be sought is also discussed. Although in everyday clinical practice the timing of surgery is not always straightforward, some newer clinical and echocardiographic indicators can guide this decision and help improve the outcome of these patients.
Project description:ImportanceThe overall prevalence of mitral valve replacement (MVR) or MV repair at the time of cardiac surgery in the setting of isolated anterior mitral leaflet degenerative pathologic status in the US population is unknown.ObjectiveTo investigate the prevalence of MVR and MV repair using the Society of Thoracic Surgeons' Adult Cardiac Surgery Database.Design, setting, and participantsIn a cross-sectional study, all patients diagnosed with isolated anterior mitral leaflet degenerative regurgitation who underwent either surgical MVR or MV repair between July 1, 2011, and June 30, 2022, were identified. Linear regression analysis was used to assess trends over time.Main outcomes and measuresAssessment of the trends in MV repair and MVR over time.ResultsA total of 16 259 patients (9624 [59.2%] men) were identified, and the median age was 68 (IQR, 58-74) years. A total of 7214 patients (44.4%) had MVR, and 9045 (55.6%) had MV repair. There was a declining trend of MV repair from 58.0% in 2011 to 51.6% in 2022 (P = .05). The MVR group was older (median [IQR] age, 70 [62-77] vs 67 [58-74] years; P < .001) and had more comorbidities. A total of 85.1% of all patients underwent concomitant procedures. In 81.7% of MVR cases, no attempt at MV repair was made. The median (IQR) annual hospital volume was lower with MVR vs MV repair (2.50 [1.50-5.00] vs 4.00 [2.00-7.00]; P < .001). Conventional surgical approaches were most common (91.5%) but with a declining trend (P < .001). Minimally invasive approaches were used in 13.1% (robotic, 4.6%), and with an inclining trend from 5.0% in 2011 to 12.0% in 2022 (P < .001). Annuloplasty was performed in 88.8% of MV repair cases. Its use as a sole mean of MV repair decreased from 48.0% in 2011 to 13.9% in 2022 (P < .001). Repair maneuvers in addition to annuloplasty were neochordae (overall 40.1%, increasing from 22.5% in 2011 to 62.3% in 2022; P < .001), leaflet resection (overall 10.2%, decreasing from 13.1% in 2011 to 7.9% in 2022, P = .002), edge-to-edge MV repair (overall 5.3%, decreasing from 6.9% in 2011 to 4.5% in 2022; P = 0.04), and chordal transfer (overall 2.4%, decreasing from 2.7% in 2011 to 0.7% in 2022; P = .004).Conclusions and relevanceIn this cross-sectional study, MV repair was the preferred option for degenerative mitral valve disease but was only slightly more commonly performed than MVR for isolated anterior leaflet pathologic status. A large proportion of MVR was performed without an MV repair attempt, suggesting reluctance to repair this pathologic condition.
Project description:AimsSex differences in prognosis of functional mitral regurgitation (FMR) associated with ischaemic cardiomyopathy (ICM) demonstrate the need to identify sex differences in cardiac remodelling. This study aimed to characterize sex differences in cardiac remodelling associated with FMR in the setting of ICM, sex interactions with cardiac remodelling and FMR severity, and predictors of all-cause mortality or heart transplantation using cardiac magnetic resonance (CMR) imaging.Methods and resultsConsecutive patients with ICM referred to CMR between 2002 and 2017 were reviewed. Eligible 790 patients [mean age: 62.0 (standard deviation = 11.2] years and 24.7% females] were evaluated over a median follow-up of 5.8 years. There were 773 subjects with complete data for survival analysis, with 449 primary events. Coronary artery disease risk factors, medications, and previous coronary revascularization were similar in females and males (all P > 0.05). Indexed left ventricular and right ventricular (LV and RV) volumes were larger in males (P < or =0.005 for all comparisons) with similar slope of increasing LV and RV volumes in the setting of increasing FMR (all P > 0.05, for interactions). However, indexed left atrial volume was similar in males and females (P = 0.696), after adjusting for FMR severity. After adjusting for medical risk factors and post-CMR procedural interventions, females demonstrated increased risk of primary clinical composite point with enlarging LV volumes [hazard ratio: 1.04 (95% confidence interval: 1.01-1.06), P = 0.034].ConclusionBecause females with increasing LV size and FMR severity demonstrated significantly increased risk of adverse outcomes, our findings suggest the importance of deriving sex-specific CMR selection criteria for therapeutic management of FMR in the setting of ICM.