Prevalence and Post-surgical Outcomes of CARdiac Wild-type TransthyrEtin amyloidoSIs in Elderly Patients With Aortic steNosis Referred for Valvular Replacement.

Cardiovascular diseases remain the major cause of mortality and morbidity in industrialised countries. Their prevalence increases steeply as consequence of the aging of the population in these countries. Curiously, cardiovascular and neurodegenerative diseases share common aging pathological pathways involving abnormal accumulation of insoluble amyloid proteins in the extracellular matrix disrupting normal organ function. Whereas neurological amyloid diseases has been considerably investigated, little attention has been paid to the aggregation of amyloid proteins in cardiovascular diseases. Post-mortem studies have identified cardiac wild-type transthyretin amyloidosis deposition in 25% of individuals over the age of 80 years leading to the concept of "senile cardiac amyloidosis" (CA) (Cornwell, Am j Med 1984; Pitkanen, Am J Pathol 1984). The cause of this deposition is not yet known but might be related primarily to aging process and enhanced by cardiac mechanical stress (overload), hypoxia, oxidative stress and inflammation. Since patients with transthyretin CA develop severe heart failure with poor prognosis, it is crucial to identify them especially among population at risk such those with aortic stenosis (AS). Indeed this common valvular heart disease affects mainly senescent subjects and combines so the adverse effects on myocardial function of both pressure overload and myocardial aging.

Interestingly, some elderly patients with severe AS exhibit similar echocardiographic and cardiac MRI patterns as those reported in CA including increased cardiac wall thickness and progressive left ventricular dysfunction starting with alteration of basal LV-2D strain. They also exhibit increased late gadolinium enhancement (LGE) at cardiac MRI. This has been interpreted as related to interstitial myocardial "fibrosis" and has been correlated with poor prognosis after aortic valve replacement i.e.; high mortality, persistence of heart failure symptoms and LV dysfunction (Weidemann Circ 2009; Dweck, JACC 2011; Hermann JACC 2011). However none of these patients have benefited from a detailed histology analysis with aiming at identifying amyloid deposits. The investigators have recently found similar clinical observations in the investigators AS cohort. Using specific staining, the investigators were able to unmask the association of severe AS and CA in these patients. These preliminary findings raise the question of a potential pathophysiological link between CA and AS and might explain why some patients with AS may not benefit from cardiac surgery.