Mechanistic insights into transient severe mitral regurgitation

<p>Acute mitral regurgitation (AMR), a known complication of acute coronary syndromes, is usually associated with posterior papillary muscle dysfunction/rupture. In severe cases, management of AMR requires surgical intervention. Reversible severe AMR in patients in the absence of left ventricular systolic dysfunction and coronary artery stenosis may result from processes which cause transient subendocardial ischemia, such as intermittent episodes of hypotension or coronary artery vasospasm. We present two cases of reversible transient AMR due to subendocardial and/or endocardial ischemia, both of which offer insight into the mechanism of transient severe AMR.</p

Mechanical properties.

<p>(A.) Stiffness comparison of native porcine, decellularized porcine with sterilization, and recellularized porcine explant after 5 months in vivo. (B.) Ultimate tensile strength comparison of native porcine, decellularized porcine implant with sterilization, and recellularized porcine explant after 5-months in vivo.</p

Gross examination.

<p>Explanted aortic valves showing aortic cusp without evidence of thrombosis, increased thickness, or calcification. Explant taken immediately after 5-month sacrifice and cross-sectioned to show anatomical features.</p

Masson’s trichrome and picrosirius red staining of porcine cusps 5-months post-explant.

<p>A) Masson’s trichrome stain (scale: 400 μm) shows ECM collagen in blue (Black arrow). Pink/Red areas are representative of nuclei and cytoplasm. B) Picrosirius Red stain (scale: 500 μm) under polarized light characterizes collagen formation.</p

Immunohistochemical characterization of aortic cusps post-explant at 5-months.

<p>Recellularization of VICs and VECs found in the aortic cusps (scale: 400 μm). Moderate endothelialization of aortic cusps on the pulmonic side observed using A.) VWF and B.) CD31 antibody. C) Representative magnification of box found in (B) showing VEC infiltration (20x) along the periphery of cusp denoted by black arrow. Infiltration of myofibroblast-like cells originating from the ventricular side observed using D.) Vimentin and E.) α-SMA antibodies. F) Representative magnification of box found in (E) showing VIC infiltration (20x) seen inside the cusp tissue denoted by black arrow.</p

Staining of porcine aortic cusps post-explant at 5-months.

<p>H&E staining representative (A) Histology section of decellularized porcine cusp prior to implantation (scale: 1000 μm). Image shows ECM intact without presence of nuclear cellular material. (B) Recellularized Aortic cusp of sheep (scale: 400 μm). Image shows intact ECM with infiltration of host-derived cells as shown in the magnified image within stain B at (20x). (C) Alizarin Red; characterization of aortic cusps post-explant at 5-months representative images (scale: 400 μm) showing absence of calcification on tissues, (D) Von Kassa; characterization of aortic cusps post-explant at 5-months representative images (scale: 400 μm) showing absence of calcification on tissues. In the case of calcification, stains C and D would show hyderdense dark areas.</p

Laboratory analysis reported in mean and standard deviation.

<p>Laboratory analysis reported in mean and standard deviation.</p

Determination of i<i>n vivo</i> valvular hemodynamics.

<p>(A) Representative echocardiographic image at 3-months. The aortic valve cusps were free of fibrosis or thickening arrow indicates aortic valve cusps. The Doppler flow confirms no valve stenosis, and gradient was measured. (B) Systolic gradients across the pulmonic valves over time measured using continuous wave Doppler echocardiography. The mean pressure gradient was elevated at one month but remained unchanged over the course of the study (P = 0.25 for mean gradient at 1- vs 5- months). (C) Hemodynamic measurement taken immediately prior to explant using invasive pulmonary artery catheters. mRAP, mean right atrial pressure; mPAP, mean pulmonary artery pressure; RVSP, right ventricular systolic pressure; PV, pulmonic valve peak to peak gradient; PCWP, pulmonary capillary wedge pressure.</p