Pathophysiology and Mechanism of Regurgitation in IMR
Although it is tempting to consider PM dysfunction or displacement, i.e. lack of contraction, as the main mechanism of regurgitation in IMR patients, animal and clinical studies have shown otherwise. In an elegant study by Kaul et. al, the investigators proved that it’s not the PM dysfunction, but MR occurs during ischemia only when global LV function is affected. This mechanism applies even when thickening of the PM and the immediately adjacent LV remains intact. MR in this situation is related to incomplete mitral leaflet closure, i.e. the less the leaflet closure the more the MR [17]. Furthermore, Aguero et. al devised a left atrial infarction swine model. The investigators showed that left atrial infarction alone leads to significant left atrial enlargement and mitral annular dilatation that may result in IMR [18].
Multiple animal and clinical studies have demonstrated that the mitral leaflet area grow due to MR [19 – 21]. Mitral valve leaflets are larger in IMR patients but fibrotic processes set in counterproductively. The endothelial-to-mesenchymal transition, an embryonic process is upregulated in these patients that leads to thickening of the leaflets of the mitral valve [22]. This study shows that despite increase in the absolute value of the mitral valve area, the profibrotic changes of the cell signaling pathways will lead to maladaptation of the coaptation of the leaflets.
Kalra et. al, in a cardiac MRI study of patients with moderate to severe IMR compared to mild MR patients demonstrated that the disposition of the PM was one of the main drivers of the regurgitation in IMR patients. In normal heart anatomy, the PMs are located below and slightly posterior to the commissures of the mitral valve leaflets. The physiologic function of the posterior PM is to move medially towards the septum and the anterior PM will follow the posterior PM and the distance between the two shortens. They measured the distance between the two PMs, defined as inter PM distance (IPMD). In this study, they noticed that the shortening of the IPMD was significantly less in IMR patients compared to controls. A cut-off point of 20mm seems to increase the risk of >moderate MR in patients with IMR. Moreover, they also showed that the reduced torsion of the posterior PM leads to increased MR. These findings elaborate the common feature of asymmetry of the line of coaptation of IMR at the level of P3 with severely posteriorly displaced P3 segment of the mitral valve leaflet, leading to severe MR and posteriorly directed jet.
The increase in preload caused by CIMR after MI is not accompanied by a parallel increase in contractility [24]. The chronic volume overload in a ventricle that has
decreased compliance causes an increase in wall stress and left atrial (LA), ventricular end-diastolic and wedge pressures. The LA and ventricle enlarge, resulting in pulmonary hypertension and congestion, leading ultimately to heart failure and death [25,26]. Ventricular dilatation increases tethering, which worsens MR severity, creating a cycle whereby MR begets MR in a self-perpetuating manner.