A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: is patient-prosthesis mismatch an independent risk factor for 30-day and mid-term overall mortality in adult patients undergoing aortic valve replacement (AVR)? Altogether, almost 400 papers were found using the reported search, of which 22 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The majority of the selected articles have focused their analysis on moderate mismatch defined mostly by the presence of an indexed effective orifice area (IEOA)0.65 cm(2)/m(2)) is an independent risk factor for 30-day or mid-term overall mortality for adult patients undergoing AVR. An exception could be represented by patients with poor ejection fraction, a condition that can make moderate mismatch a predictor of overall mortality after AVR. On the other hand, severe mismatch is a predictor of overall 30-day or mid-term mortality for patients undergoing AVR independently from the presence of poor ejection fraction. In conclusion, our review suggests that the condition of severe PPM should be always avoided, while the presence of moderate mismatch could be tolerated in patients with normal ejection fraction without any impact on overall survival.

1 Vasospasm of arterial conduits used for coronary artery surgery is an important cause of graft failure and is likely to result partly from raised levels of vasoconstrictor substances such as thromboxane A 2 and endothelin-1. Our aim was to ®nd pharmacological agents that could prevent agonist-induced vasospasm. 2 Isometric tension was recorded from discarded segments of human left internal mammary artery (LIMA). Submaximal contraction evoked by the thromboxane A 2 mimetic U46619 (10 nM) was not inhibited by a blocker of store-and receptor-operated Ca 2+ channels (30 mM SKF96365) in the presence of diltiazem. Furthermore, contractions to 41 nM U46619 were preserved when extracellular Ca 2+ was reduced from 2.5 mM to 60 nM. Thus, sustained U46619-evoked contraction occurred without Ca 2+ in¯ux. 3 We hypothesized that contraction might occur via Rho-kinase-mediated Ca 2+ -sensitization of myo®laments. Inhibitors of Rho-kinase (Y27632 and HA1077) were profound relaxants. If contraction was pre-evoked by 10 nM U46619, Y27632 and HA1077 caused full relaxation with EC 50 s of 1.67+0.22 mM and 3.58+0.35 mM respectively. Y27632 was also eective if applied before U46619, but was less potent. 4 Y27632 abolished contraction evoked by endothelin-1 and signi®cantly reduced resting tone in the absence of a vasoconstrictor. 5 Rho-kinase-mediated Ca 2+ -sensitization appears to be a major mechanism of vasoconstriction in human LIMA. Rho-kinase inhibitors may have an important role in preventing vasospasm in arterial grafts used for coronary artery surgery.

Aldosterone (Aldo) contributes to mitochondrial dysfunction and cardiac oxidative stress. Using a proteomic approach, A-kinase anchor protein (AKAP)-12 has been identified as a down-regulated protein by Aldo in human cardiac fibroblasts. We aim to characterize whether AKAP-12 down-regulation could be a deleterious mechanism which induces mitochondrial dysfunction and oxidative stress in cardiac cells. Aldo down-regulated AKAP-12 via its mineralocorticoid receptor, increased oxidative stress and induced mitochondrial dysfunction characterized by decreased mitochondrial-DNA and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expressions in human cardiac fibroblasts. CRISPR/Cas9-mediated knock-down of AKAP-12 produced similar deleterious effects in human cardiac fibroblasts. CRISPR/Cas9-mediated activation of AKAP-12 blunted Aldo effects on mitochondrial dysfunction and oxidative stress in human cardiac fibroblasts. In Aldo-salt-treated rats, cardiac AKAP-12, mitochondrial-DNA and PGC-1α expressions were decreased and paralleled increased oxidative stress. In myocardial biopsies from patients with aortic stenosis (AS, n = 26), AKAP-12, mitochondrial-DNA and PGC-1α expressions were decreased as compared to Controls (n = 13). Circulating Aldo levels inversely correlated with cardiac AKAP-12. PGC-1α positively associated with AKAP-12 and with mitochondrial-DNA. Aldo decreased AKAP-12 expression, impairing mitochondrial biogenesis and increasing cardiac oxidative stress. AKAP-12 down-regulation triggered by Aldo may represent an important event in the development of mitochondrial dysfunction and cardiac oxidative stress.