Challenges and pitfalls in classification of disproportionate mitral regurgitation.

The concept of disproportionate mitral regurgitation (dispropMR) has been introduced to identify patients with functional mitral regurgitation (MR) who benefit from percutaneous treatment. We aimed to examine echocardiographic characteristics behind this entity. We retrospectively included 172 consecutive patients with reduced left ventricular ejection fraction (LVEF), and more than mild MR referred to clinically indicated echocardiography. According to the proportionality ratio (effective regurgitant orifice area (EROA)/left ventricular end-diastolic volume (LVEDV)) patients were divided into dispropMR and proportionate MR (propMR) group. Potential factors which might affect proportionality definition were analyzed. 55 patients (32%) had dispropMR. Discrepant grading of MR severity was observed when using regurgitant volume (RegVol) by proximal isovelocity surface area (PISA) method or volumetric method, with significant discordance only in dispropMR (p < 0.001). Patients with dispropMR had more frequently left ventricular foreshortened images for LVEDV calculation than patients with propMR (p = 0.003), resulting in smaller LVEDV in dispropMR group. DispropMR group had more substantial dynamic variation of regurgitant flow compared to propMR. Accordingly, EROA was consistently overestimated by standard single-point PISA method compared to serial PISA method. This was more pronounced in dispropMR (bias:10.5 ± 28.3 mm2) compared to propMR group (bias:6.4 ± 12.8 mm2). DispropMR may be found in roughly one third of clinically indicated echocardiographic studies in patients with reduced LVEF and more than mild MR. EROA overestimation due to dynamic variation of regurgitant flow and LVEDV underestimation due to LV foreshortening were more frequently found in dispropMR. Our results indicate that methodological limitations of echocardiographic MR grading could not be neglected in classifying the proportionality of MR.

New Evidence Supporting a Novel Conceptual Framework for Distinguishing Proportionate and Disproportionate Functional Mitral Regurgitation.

Importance: Traditionally, physicians distinguished between mitral regurgitation (MR) as a determinant of outcomes and MR as a biomarker of left-ventricular (LV) dysfunction by designating the lesions as primary or secondary, respectively. In primary MR, leaflet abnormalities cause the MR, resulting in modest increases in LV end-diastolic volume over time, whereas in patients with classic secondary MR, LV dysfunction and dilatation lead to MR without structural leaflet abnormalities. However, certain patients with global LV disease (eg, those with left bundle branch block or regional wall motion abnormalities) have the features of primary MR and might respond favorably to interventions that aim to restore the proper functioning of the mitral valve apparatus. Observations: A novel conceptual framework is proposed, which classifies patients with meaningful LV disease based on whether the severity of MR is proportionate or disproportionate to the LV end-diastolic volume. Treatments that reduce LV volumes (eg, neurohormonal antagonists) are effective in proportionate MR but not disproportionate MR. Conversely, procedures that restore mitral valve function (eg, cardiac resynchronization and mitral valve repair) are effective in patients with disproportionate MR but not in those with proportionate MR. The proposed framework explains the discordant findings in the Multicentre Randomized Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation (MITRA-FR) and the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trials; differences in procedural success and medical therapy in the 2 studies cannot explain the different results. In addition, the small group of patients in the COAPT trial who had the features of proportionate MR and were similar to those enrolled in the MITRA-FR trial did not respond favorably to transcatheter mitral valve repair. Conclusions and Relevance: The characterization of patients with functional MR into proportionate and disproportionate subtypes may explain the diverse range of responses to drug and device interventions that have been observed.

Misclassification of Mitral Valve Disease and Rate of Surgical Repair in The Society of Thoracic Surgeons Database.

BACKGROUND: Surgical repair of primary mitral regurgitation (MR) is considered an indicator of quality performance. Therefore, accurate data reporting is critical for quality assessment. During an institutional quality review, MR etiology could not be determined in 40% of operations in The Society of Thoracic Surgeons database entries, and therefore our true repair rate could not be reliably ascertained. Therefore, we reviewed all source documents and echocardiograms to assess our true disease etiology and repair rate. METHODS: Source records and echocardiograms of all operations performed in a single health care system for a 1-year period were reviewed by an experienced mitral valve surgeon, an echocardiographic core laboratory, and a data manager. Disease etiology and operation were compared with data previously entered in the database by post hoc chart abstraction. RESULTS: In all, 314 isolated mitral valve operations were performed. The MR was originally classified as primary, 163 (52%); secondary, 22 (7%); rheumatic, 37 (12%); endocarditis, 24 (8%); other, 33 (10%); and unknown, 35 (11%). Reported repair rate for primary MR was 142 of 163 (87.1%). After review, etiology was determined to be primary, 177 (56%); secondary, 33 (11%); rheumatic, 61 (20%); endocarditis, 25 (8%); and others, 18 (5%)-resulting in a change of classification in 99 of 314 patients (31.5%) and a true repair rate for primary MR of 165 of 177 (93.2%). CONCLUSIONS: Source document and imaging review of mitral valve surgery revealed significant discordance with post hoc chart abstraction methods. A more detailed data entry methodology is necessary to accurately report the true disease etiology and repair rates for primary MR.

Functional mitral regurgitation, updated: ventricular or atrial?

Lone atrial fibrillation (AF) can cause functional mitral regurgitation (MR), commonly referred to as "atrial functional MR (AFMR)." This type of MR has recently received much attention as an important cause of heart failure, and it represents a considerable therapeutic target in heart failure patients with AF. Mitral annular dilatation due to left atrial (LA) dilatation can be recognized as an original cause of AFMR, whereas the exact cascade of AFMR etiologies has not been established. AFMR is typically classified as Carpentier type I, and is likely to have a central jet. In contrast, a proportion of AFMR is classified as a combination of Carpentier type I for a flattened anterior mitral leaflet and Carpentier type IIIb for a tethered posterior mitral leaflet and is likely to have an eccentric jet directed toward the LA posterior wall. The traditional functional MR occurring in patients with left ventricular (LV) dilatation and/or systolic dysfunction, which is classified as Carpentier type IIIb, has since been designated "ventricular functional MR (VFMR)" to distinguish it from AFMR. Traditional VFMR, newly recognized AFMR, and their etiologic relations to LV/LA size and function are discussed in this review article.

[Percutaneous treatment of mitral regurgitation]. / Prise en charge interventionnelle de la fuite mitrale.

Mitral regurgitation (MR) is currently the most frequent valvular heart disease, and the second most operated valve in Europe. Around 50% of patients presenting severe MR are denied surgery, despite the adverse prognosis associated with the absence of treatment, due to comorbidities and/or advanced age. During the previous years, percutaneous treatment of MR, whether by replacement or, more frequently, by repair, has been developed, providing an alternative for those patients who are deemed at prohibitive, but also, high surgical risk. Percutaneous edge-to-edge repair is currently the most frequently used technique, and is the only one recommended by the European Guidelines for Valvular Heart Disease Management. In the current article, we review the different strategies for MR repair, as well as the indications and level of evidence for their use.

Echocardiographic assessment of functional mitral regurgitation: opening Pandora's box?

Two recent trials of transcatheter mitral-valve repair in patients with functional mitral regurgitation (FMR) presented opposing results for the MitraClip® compared to medical therapy alone. The conflicting results gave rise to intensive discussions about assessment of mitral valve regurgitation (MR). A recent editorial viewpoint provided a potential explanation presenting a new pathophysiologic concept. However, the echocardiographic characterization of both trials' patients is inconsistent and the discussed concepts appear to suffer from plausibility weaknesses. It is well conceivable that limitations in the echocardiographic assessment of the trial patients introduced a bias regarding the selection of patients with severe (or less severe) MR that may be a more plausible explanation for the differences in outcome. We here illustrate our viewpoint regarding the two MitraClip trials and also illustrate the difficulties in assessing functional MR properly. It may indeed be "opening Pandora's box", but we will also make an attempt to provide a solution.

Transcatheter Edge-to-Edge Repair for Primary (Degenerative) Mitral Regurgitation: Registries and Trials.

The MitraClip is the only approved transcatheter edge-to-edge repair device that is commercially available for the treatment of severe, symptomatic, primary (degenerative) mitral regurgitation in patients deemed to be at prohibitive risk by a heart team. Transcatheter edge-to-edge repair can be safely performed with a low rate of periprocedural adverse events despite a predominantly elderly patient population with multiple comorbidities. Transcatheter edge-to-edge repair is associated with improvement in mitral regurgitation severity; left ventricular dimensions and remodeling; heart failure rehospitalizations; and, in high-risk groups, an improvement in survival compared with medical therapy.

Transcatheter Mitral Valve Replacement with Intrepid.

Transcatheter mitral valve replacement with the Intrepid device is intended for patients who need mitral valve replacement and who are at an increased risk for conventional surgery. The early published results of the early feasibility trial are reviewed as well as device design and the implant procedure. The Apollo trial is reviewed: a randomized trial of the Intrepid device versus conventional surgery including a single arm study for inoperable patients. The mitral valve structure, pathophysiology, and postimplant physiology pose unique hurdles for any transcatheter implant.

Minimally invasive mitral valve repair for functional mitral regurgitation.

Systolic heart failure is frequently accompanied by a relevant functional mitral valve regurgitation (FMR) which develops as a direct sequela of the ongoing left ventricular remodelling. The severity of mitral regurgitation is further aggravated by progressive left ventricular enlargement causing leaflet tethering and reduced systolic leaflet movement. The prognosis of such patients is obviously limited by an underlying left ventricular disease, and the correction of secondary FMR has been previously suggested as predominantly 'cosmetic' surgery in the setting of ongoing cardiomyopathy. Inferior results of an isolated annuloplasty in type IIIb FMR supported the philosophy of malignant course of progressive cardiomyopathy and resulted in increasingly restricted indications for mitral valve surgery for FMR in the guidelines. The lack of a standardized pathophysiological approach to correct type IIIb FMR led to the development of valve replacement strategy and edge-to-edge catheter-based mitral valve procedures, which became the most frequent procedures in the FMR setting in Europe. Modern mitral valve surgery combines the advantages of 3-dimensional endoscopic minimally invasive surgical approach with standardized subannular repair to address the pathophysiological background of type IIIb FMR. The perioperative results have been significantly improved, and there is a growing evidence of improved long-term stability of subannular repair procedures as compared to isolated annuloplasty. This review article aims to present the current state-of-the-art of the modern mitral valve surgery in FMR and provides suggestions for future trials analysing the potential advantages in these patients.

Causes and mechanisms of isolated mitral regurgitation in the community: clinical context and outcome.

AIMS: To define the hitherto unknown aetiology/mechanism distributions of mitral regurgitation (MR) in the community and the linked clinical characteristics/outcomes. METHODS AND RESULTS: We identified all isolated, moderate/severe MR diagnosed in our community (Olmsted County, MN, USA) between 2000 and 2010 and classified MR aetiology/mechanisms. Eligible patients (n = 727) were 73 ± 18 years, 51% females, with ejection fraction (EF) 49 ± 17%. MR was functional (FMR) in 65%, organic (OMR) in 32% and 2% mixed. Functional MR was linked to left ventricular remodelling (FMR-v) 38% and isolated atrial dilatation (FMR-a) 27%. At diagnosis FMR-v vs. FMR-a, vs. OMR displayed profound differences (all P < 0.0001) in age (73 ± 14, 80 ± 10, 68 ± 21years), male-sex (59, 33, 51%), atrial-fibrillation (28, 54, 13%), EF (33 ± 14, 57 ± 11, 61 ± 10%), and regurgitant-volume (38 ± 13, 37 ± 11, 51 ± 24 mL/beat). Dominant MR mechanism was Type I (normal valve-movement) 38%, Type II (excessive valve-movement) 25%, Type IIIa (diastolic movement-restriction) 3%, and Type IIIb (systolic movement-restriction) 34%. Outcomes were mediocre with excess-mortality vs. general-population in FMR-v [risk ratio 3.45 (2.98-3.99), P < 0.0001] but also FMR-a [risk ratio 1.88 (1.52-2.25), P < 0.0001] and OMR [risk ratio 1.83 (1.50-2.22), P < 0.0001]. Heart failure was frequent, particularly in FMR-v (5-year 83 ± 3% vs. 59 ± 4% FMR-a, 40 ± 3% OMR, P < 0.0001). Mitral surgery during patients' lifetime was performed in 4% of FMR-v, 3% of FMR-a, and 37% of OMR. CONCLUSION: Moderate/severe isolated MR in the community displays considerable aetiology/mechanism heterogeneity. Functional MR dominates, mostly FMR-v but FMR-a is frequent and degenerative MR dominates OMR. Outcomes are mediocre with excess-mortality particularly with FMR-v but FMR-a, despite normal EF incurs notable excess-mortality and frequent heart failure. Pervasive undertreatment warrants clinical trials of therapies tailored to specific MR cause/mechanisms.

Interventional treatment of mitral valve regurgitation: an alternative to surgery?

Mitral regurgitation is a highly prevalent condition among elderly patients, affecting almost 10% of the general population aged 75 and older. Left untreated, severe mitral regurgitation results in high mortality and frequent hospitalisation for treatment of heart failure. Surgical treatment remains the first-line therapy for symptomatic, severe mitral regurgitation , especially for patients presenting with a primary aetiology. However, a high proportion of patients with mitral regurgitation are turned down for open-heart surgery, mainly due to advanced age, diminished left ventricular function and comorbidities. Thus, percutaneous treatment options have been recently developed as an alternative. In this article, we will review transcatheter interventional techniques at the level of the mitral valve, including implantation technique, indications and clinical results.

Minimally Invasive Mitral Valve Annuloplasty With Realignment of Both Papillary Muscles for Correction of Type IIIb Functional Mitral Regurgitation.

OBJECTIVE: Pathophysiological background of type IIIb functional mitral regurgitation (FMR) is a progressively increasing distance between papillary muscle tips and mitral annular plane. Standard surgical treatment of such FMR by means of undersized mitral annuloplasty is associated with a high recurrence rate. METHODS: We propose a modified subannular maneuver to correct type IIIb FMR while combining undersized annuloplasty with a controlled realignment of both papillary muscles, thereby fixing the distance between mitral annular plane and papillary muscle tips. The differences of this subannular maneuver as compared with the previously published techniques are the following: (1) controlled realignment of both papillary muscles, (2) fixation of the papillary muscles to mitral annulus distance on an annuloplasty ring, and (3) application in a three-dimensional endoscopic minithoracotomy setting. RESULTS: We describe a surgical technique of minimally invasive mitral valve repair performed due to severe type IIIb FMR, which includes a modified subannular maneuver to realign both papillary muscles. Preliminary results of the first 10 patients who underwent this procedure at our institution are presented. There was no in-hospital mortality and follow-up echocardiography (mean ± SD echocardiographic follow-up = 10 ± 6 months) demonstrated stable functional results. CONCLUSIONS: Our initial experience indicates that adding of this subannular maneuver to the standard annuloplasty and thereby fixing the distance between papillary muscles and mitral annular plane have a potential to improve results of surgical FMR treatment.

Valvular Heart Disease in Adults: Etiologies, Classification, and Diagnosis.

The prevalence of valvular heart disease (VHD) in the United States was estimated to be approximately 2.5% in the 1990s. The prevalence currently is thought to be increasing because of more accurate diagnostic methods and aging of the population. Mitral regurgitation (MR) is the most common valve defect, followed by aortic stenosis (AS) and aortic regurgitation (AR). Degenerative disease is the most common etiology of MR, AS, and AR, though these forms of VHD also can be caused by congenital valve defects, systemic inflammatory diseases, endocarditis, and many other conditions. Mitral stenosis, most often caused by rheumatic fever, is uncommon in the United States. When VHD is suspected, transthoracic echocardiography should be obtained first. Other tests, including transesophageal echocardiography, computed tomography scan, magnetic resonance imaging study, and cardiac catheterization, are used in special situations to obtain more detailed diagnostic information. Guidelines for VHD management recommend interval monitoring with echocardiography. The exact interval recommended depends on the severity of the valve dysfunction and whether the patient is symptomatic. Monitoring of asymptomatic patients is important because early intervention, when valve function worsens or symptoms develop, is associated with better outcomes.

Mitral Regurgitation Grading in the Operating Room: A Systematic Review and Meta-analysis Comparing Preoperative and Intraoperative Assessments During Cardiac Surgery.

OBJECTIVE: To assess differences in mitral regurgitation (MR) grade between the preoperative and the intraoperative evaluations. DESIGN: Systematic review and meta-analysis of 6 observational studies found from MEDLINE and EMBASE. SETTING: Cardiac surgery. PARTICIPANTS: One hundred thirty-seven patients. INTERVENTION: Comparison between the preoperative MR assessment and the intraoperative evaluation conducted under general anesthesia (GA), with or without "hemodynamic matching" (HM) (artificial increase of afterload). MEASUREMENTS AND MAIN RESULTS: The primary outcome was the difference between the preoperative and intraoperative MR grade under "GA-only" or "after-HM." Secondary analyses addressed differences according to effective regurgitant orifice area (EROA), regurgitant volume (RVol), color-jet area, and vena contracta width. Risk of MR underestimation was found under "GA-only" (SMD: 0.55; 95% confidence interval [CI], 0.31-0.79, p < 0.00001), but not "after-HM" (SMD: -0.16; 95% CI, -0.46 to 0.13, p = 0.27). Under "GA-only", EROA had a trend toward underestimation (p = 0.07), RVol was reliable (p = 0.17), while reliance on color-jet area and vena contracta width incur risk of underestimation (both p = 0.003). After HM, EROA accurately reflected preoperative MR (p = 0.68) while RVol had a trend toward overestimation (p = 0.05). The overall reported incidence of misdiagnoses was slightly more common under "GA-only" (mean 48%, 39% underestimation, 9% overestimation; range: 32%-57%) than "after-HM" (mean 41%, 12% underestimation, 29% overestimation; range: 33%-50%). Only the minority of misdiagnoses were clinically relevant: underestimation was around 10% (both approaches), but 18% had clinically significant overestimation "after-HM" as compared with 3% under GA-only. CONCLUSIONS: Intraoperative assessment under "GA-only" significantly underestimated MR. A more accurate intraoperative evaluation can be obtained with afterload manipulation, although HM strategy carries high risk of clinically significant overestimation.

Parameters indicative of persistence of valvular pathology at initial diagnosis in acute rheumatic carditis: the role of albumin and CD19 expression / Parâmetros indicativos de persistência de patologia valvular no diagnóstico inicial de cardite reumática aguda: o papel da albumina e da expressão de CD19

Abstract Objective: The aim of this study is to define the predictors of chronic carditis in patients with acute rheumatic carditis (ARC). Methods: Patients diagnosed with ARC between May 2010 and May 2011 were included in the study. Echocardiography, electrocardiography, lymphocyte subset analysis, acute phase reactants, plasma albumin levels, and antistreptolysin-O (ASO) tests were performed at initial presentation. The echocardiographic assessments were repeated at the sixth month of follow-up. The patients were divided into two groups according to persistence of valvular pathology at 6th month as Group 1 and Group 2, and all clinical and laboratory parameters at admission were compared between two groups of valvular involvement. Results: During the one-year study period, 22 patients had valvular disease. Seventeen (77.2%) patients showed regression in valvular pathology. An initial mild regurgitation disappeared in eight patients (36.3%). Among seven (31.8%) patients with moderate regurgitation initially, the regurgitation disappeared in three, and four patients improved to mild regurgitation. Two patients with a severe regurgitation initially improved to moderate regurgitation (9.1%). In five (22.8%) patients, the grade of regurgitation [moderate regurgitation in one (4.6%), and severe regurgitation in 4 (18.2%)] remained unchanged. The albumin level was significantly lower at diagnosis in Group 2 (2.6 ± 0.48 g/dL). Lymphocyte subset analysis showed a significant decrease in the CD8 percentage and a significant increase in CD19 percentage at diagnosis in Group 2 compared to Group 1. Conclusion: The blood albumin level and the percentage of CD8 and CD19 (+) lymphocytes at diagnosis may help to predict chronic valvular disease risk in patients with acute rheumatic carditis.

Resumo Objetivo: Definir os preditores da cardite crônica em pacientes com cardite reumática aguda (CRA). Métodos: Os pacientes diagnosticados com CRA entre maio de 2010 e maio de 2011 foram incluídos no estudo. Foram feitos os testes de ecocardiografia, eletrocardiograma, uma análise do subgrupo de linfócitos, provas de fase aguda, níveis de albumina plasmática, antiestreptolisina-O (ASO) na manifestação inicial. As avaliações ecocardiográficas foram repetidas no 6º mês de acompanhamento. Os pacientes foram divididos em dois grupos de acordo com a persistência da patologia valvular no 6º mês como Grupo 1 e Grupo 2 e todos os parâmetros clínicos e laboratoriais na internação foram comparados entre dois grupos de comprometimento valvular. Resultados: Durante o período do estudo de um ano, 22 pacientes apresentaram doença valvular; 17 (77,2%) apresentaram regressão da patologia valvular. Houve desaparecimento de regurgitação moderada inicial em oito pacientes (36,3%). Entre sete (31,8%) pacientes com regurgitação moderada inicialmente, a regurgitação desapareceu em três e quatro apresentaram melhoria para regurgitação leve. Dois pacientes com regurgitação grave inicialmente apresentaram melhoria para regurgitação moderada (9,1%). Em cinco (22,8%) pacientes o grau de regurgitação (regurgitação moderada em um [4,6%] e regurgitação grave em quatro [18,2]) continuou inalterado. O nível de albumina foi significativamente menor no diagnóstico no Grupo 2 (2,6 ± 0,48 gr/dL). A análise do subgrupo de linfócitos mostrou uma redução significativa no percentual de CD8 e um aumento significativo no percentual de CD19 no Grupo 2 em comparação com o Grupo 1. Conclusão: O nível de albumina no sangue e o percentual de linfócitos CD8 e CD19 (+) no diagnóstico podem ajudar a prever risco de doença valvular crônica em pacientes com cardite reumática aguda.

Parameters indicative of persistence of valvular pathology at initial diagnosis in acute rheumatic carditis: the role of albumin and CD19 expression.

OBJECTIVE: The aim of this study is to define the predictors of chronic carditis in patients with acute rheumatic carditis (ARC). METHODS: Patients diagnosed with ARC between May 2010 and May 2011 were included in the study. Echocardiography, electrocardiography, lymphocyte subset analysis, acute phase reactants, plasma albumin levels, and antistreptolysin-O (ASO) tests were performed at initial presentation. The echocardiographic assessments were repeated at the sixth month of follow-up. The patients were divided into two groups according to persistence of valvular pathology at 6th month as Group 1 and Group 2, and all clinical and laboratory parameters at admission were compared between two groups of valvular involvement. RESULTS: During the one-year study period, 22 patients had valvular disease. Seventeen (77.2%) patients showed regression in valvular pathology. An initial mild regurgitation disappeared in eight patients (36.3%). Among seven (31.8%) patients with moderate regurgitation initially, the regurgitation disappeared in three, and four patients improved to mild regurgitation. Two patients with a severe regurgitation initially improved to moderate regurgitation (9.1%). In five (22.8%) patients, the grade of regurgitation [moderate regurgitation in one (4.6%), and severe regurgitation in 4 (18.2%)] remained unchanged. The albumin level was significantly lower at diagnosis in Group 2 (2.6±0.48g/dL). Lymphocyte subset analysis showed a significant decrease in the CD8 percentage and a significant increase in CD19 percentage at diagnosis in Group 2 compared to Group 1. CONCLUSION: The blood albumin level and the percentage of CD8 and CD19 (+) lymphocytes at diagnosis may help to predict chronic valvular disease risk in patients with acute rheumatic carditis.