A 38-year-old obese man presented to our outpatients’ clinic for progressive dyspnea and chest pain during exertion. The patient had a history of percutaneous patent foramen ovale closure, uncontrolled hypertension and congenital bilateral cataract. At the clinical evaluation a new ejective systolic murmur on the aortic area was revealed. He had neither crackles, nor hepatomegaly, nor extremity edema. His vital signs were: blood pressure 170/75 mm Hg, heart rate 80 beats/min and oxygen saturation 98% on room air. Electrocardiogram showed a first-degree atrio-ventricular block and left ventricular hypertrophy.
Transthoracic echocardiography showed: a slightly reduced left ventricular ejection fraction of about 50%, with a severe left ventricle dilatation and mild left atrial dilatation (LVEDVi 133 ml/m2, LAVi 40 ml/m2), severe aortic regurgitation with Vena Contracta > 8 mm and a mobile ill-defined subaortic structure prolapsing into the left ventricular outflow tract (LVOT) causing a severe LVOT obstruction (peak/mean gradient 129/73 mmHg).
Identification of a mobile structure in the LVOT gives rise to concern for vegetation, cusp flail, subaortic membrane, redundant mitral valve chordae, primary or secondary cardiac tumors, and accessory mitral valve tissue.
To better characterize this finding, a transesophageal echocardiography (TEE) was performed. On the standard mid-esophageal long axis view, an abnormal movement of the aortic right coronary cusp, losing the coaptation point and everting totally in the LVOT was revealed (Figure-1, A,B) and confirmed on 3D reconstruction (Figure-1,C).
This finding was interpreted as a right coronary cusp flail, which was consistent with the severe aortic regurgitation but not with the LVOT gradient. Therefore, a CT angiography was performed in order to exclude an associated aortic dissection and to evaluate the epicardial coronary arteries before a possible surgery. At the radiological evaluation, no signs of aortic dissection or obstructive coronary artery disease were observed.
Patient’s symptoms together with the echocardiographic findings made the surgical solution recommended. Intraoperative inspection of the aortic valve showed a tricuspid aortic valve with a fibromuscular metaplasia of the cusps structure and a delamination of the right coronary cusp, splitting in two layers: one layer adhering to the valve annulus and the other protruding into the LVOT (Figure-1, D). The native aortic valve was then removed and a mechanical prostheses was implanted. The patient had a regular peri-operative course without complications.
In humans and animals models, valve cellular and extra cellular integrity is actively maintained in a homeostatic balance by paracrine interactions between valve interstitial cells (VIC) and valve endothelial cells (VEC), which inhibit endothelial-to-mesenchymal transition. The exposure to different types of stress entails a valve change in dimension, shape and stiffness secondary to the interaction between cells and extracellular matrix [1].
Several studies demonstrated the role of TGFβ overexpression in the development of lens opacity in patients with congenital cataract.
In VIC and VEC environment, TGFβ can activate mesenchymal signaling programs and in canine valve cultures the combination of TGFβ1 overexposure and cyclic strain induced myofibroblastic differentiation in VIC [2].
Uncontrolled hypertension is a cause of excessive shear stress and together with an anomalous autocrine and paracrine signalling pathway, involving TGFβ cascade, may result in valve metaplasia and disruption.
These mechanisms could explain the peculiar finding of a cusp delamination causing severe valve regurgitation and the presence of valve muscular metaplasia projecting through the LVOT.
Valve tissue remodeling is a complex process, where genes and environment act together to produce the valve phenotype. The genetic predisposition in an adult with a congenital eye disease associated with the mechanical stress of arterial hypertension led to a peculiar fibromuscular degeneration of the aortic valve with the need of surgical replacement. Echocardiography played an important role for working diagnosis but surgical evaluation was essential to characterize this unusual condition.