Secondary mitral regurgitation: pathophysiology, proportionality and prognosis

Abstract

Secondary mitral regurgitation (SMR) occurs as a result of multifactorial left atrioventricular dysfunction and maleficent remodelling. It is the most common and undertreated form of mitral regurgitation (MR) and is associated with a very poor prognosis. Whether SMR is a bystander reflecting the severity of the cardiomyopathy disease process has long been the subject of debate. Studies suggest that SMR is an independent driver of prognosis in patients with an intermediate heart failure (HF) phenotype and not those with advanced HF. There is also no universal agreement regarding the quantitative thresholds defining severe SMR and indeed there are challenges with echocardiographic quantification. Until recently, no surgical or transcatheter intervention for SMR had demonstrated prognostic benefit, in contrast with HF medical therapy and cardiac resynchronisation therapy. In 2018, the first two randomised controlled trials (RCTs) of edge-to-edge transcatheter mitral valve repair versus guideline-directed medical therapy in HF (Percutaneous Repair with the MitraClip Device for Severe (MITRA-FR), Transcather mitral valve repair in patients with heart failure (COAPT)) reported contrasting yet complimentary results. Unlike in MITRA-FR, COAPT demonstrated significant prognostic benefit, largely attributed to the selection of patients with disproportionately severe MR relative to their HF phenotype. Consequently, quantifying the degree of SMR in relation to left ventricular volume may be a useful discriminator in predicting the success of transcatheter intervention. The challenge going forward is the identification and validation of such parameters while in parallel maintaining a heart-team guided holistic approach.

Surgical versus transcatheter mitral valve replacement in functional mitral valve regurgitation

“…Functional (or secondary) mitral regurgitation (FMR) is a pathologic process that occurs due to anatomic aberrancies of the left ventricle (LV), subvalvular apparatus, or left atrium in the setting of structurally normal valve leaflets (1). Causes of FMR are further subclassified as ischemic (the result of myocardial injury and adverse LV remodeling) or non-ischemic (2).…”

“…With worsening MR, maladaptation of ventricular geometry can further beget MR through annular dilation as well as ongoing LV dysfunction, causing malcoaptation of valve leaflets (5)(6)(7). Myocardial fibrosis leads to worsening LV function further perpetuating the pathophysiologic state (1,3). Overall prognosis is worse when interventions are performed after symptoms have developed (1,5,6).…”

“…Myocardial fibrosis leads to worsening LV function further perpetuating the pathophysiologic state (1,3). Overall prognosis is worse when interventions are performed after symptoms have developed (1,5,6). Poor outcomes for ischemic mitral regurgitation (IMR) are present at even more restrictive criteria as compared to primary MR, effective regurgitant orifice (ERO) ≥0.2 vs. 0.4 cm 2 , respectively (4).…”

Predictors for procedural success and all-cause mortality in patients undergoing transcatheter mitral valve edge-to-edge repair for mitral regurgitation

“…In PMR patients, structural damage of different parts of the valvular apparatus itself can lead to development of MR, while SMR is caused by atrial and ventricular pathologies [4] . Accordingly, PMR and SMR themselves form heterogeneous groups and can occur in combination, a fact which must be taken into account for therapeutic decisions and device selection [5] . In PMR, TMVr is recommended in case of prohibitive surgical risk and absence of adverse anatomic features, based on the results of the EVEREST (Endovascular Valve Edge-to-Edge Repair Study) trials [6][7][8] .…”

Transcatheter mitral valve intervention in advanced heart failure

“…This worsening in the regurgitant volume leads to progression in the clinical and functional aspects of advanced heart failure and adversely influences prognosis. 3 Interrupting this vicious cycle is therefore of critical importance as a therapeutic target in advanced heart failure.…”