Marco Luciani

OBJECTIVES: Prosthetic valve endocarditis (PVE) is an uncommon yet dreadful complication in patients with prosthetic valves that requires a distinct analysis from native valve endocarditis. The present study aims to investigate independent risk factors for early surgical outcomes in patients with PVE. METHODS: A retrospective cohort study was conducted in 8 Italian Cardiac Surgery Units from January 2000 to December 2013 by enrolling all PVE patients undergoing surgical treatment. RESULTS: A total of 209 consecutive patients were included in the study. During the study period, the global rate of surgical procedures for PVE among all operations for isolated or associated valvular disease was 0.45%. Despite its rarity this percentage increased significantly during the second time frame (2007-2013) in comparison with the previous one (2000-2006): 0.58% vs 0.31% (P < 0.001). Intraoperative and in-hospital mortality rates were 4.3% and 21.5%, respectively. Logistic regression analysis identified the following factors associated with in-hospital mortality: female gender [odds ratio (OR) = 4.62; P < 0.001], shock status (OR = 3.29; P = 0.02), previous surgical procedures within 3 months from the treatment (OR = 3.57; P = 0.009), multivalvular involvement (OR = 8.04; P = 0.003), abscess (OR = 2.48; P = 0.03) and urgent surgery (OR = 6.63; P < 0.001). CONCLUSIONS: Despite its rarity, PVE showed a significant increase over time. Up to now, in-hospital mortality after surgical treatment still remains high (>20%). Critical clinical presentation and extension of anatomical lesions are strong preoperative predictors for poor early outcome.

BACKGROUND: Amyloid plaques and neurofibrillary tangles, the molecular lesions that characterize Alzheimer's disease (AD) and other forms of dementia, are emerging as determinants of proteinopathies 'beyond the brain'. This study aims to establish tau's putative pathophysiological mechanistic roles and potential future therapeutic targeting of tau in heart failure (HF). METHODS AND RESULTS: A mouse model of tauopathy and human myocardial and brain tissue from patients with HF, AD, and controls was employed in this study. Tau protein expression was examined together with its distribution, and in vitro tau-related pathophysiological mechanisms were identified using a variety of biochemical, imaging, and functional approaches. A novel tau-targeting immunotherapy was tested to explore tau-targeted therapeutic potential in HF. Tau is expressed in normal and diseased human hearts, in contradistinction to the current oft-cited observation that tau is expressed specifically in the brain. Notably, the main cardiac isoform is high-molecular-weight (HMW) tau (also known as big tau), and hyperphosphorylated tau segregates in aggregates in HF and AD hearts. As previously described for amyloid-beta, the tauopathy phenotype in human myocardium is of diastolic dysfunction. Perturbation in the tubulin code, specifically a loss of tyrosinated microtubules, emerged as a potential mechanism of myocardial tauopathy. Monoclonal anti-tau antibody therapy improved myocardial function and clearance of toxic aggregates in mice, supporting tau as a potential target for novel HF immunotherapy. CONCLUSION: The study presents new mechanistic evidence and potential treatment for the brain-heart tauopathy axis in myocardial and brain degenerative diseases and ageing.

BACKGROUND: Diabetes is associated with prolongation of the QT interval of the electrocardiogram and enhanced dispersion of ventricular repolarization, factors that, together with atherosclerosis and myocardial ischemia, may promote the occurrence of electrical disorders. Thus, we tested the possibility that alterations in transmembrane ionic currents reduce the repolarization reserve of myocytes, leading to action potential (AP) prolongation and enhanced beat-to-beat variability of repolarization. METHODS AND RESULTS: Diabetes was induced in mice with streptozotocin (STZ), and effects of hyperglycemia on electrical properties of whole heart and myocytes were studied with respect to an untreated control group (Ctrl) using electrocardiographic recordings in vivo, ex vivo perfused hearts, and single-cell patch-clamp analysis. Additionally, a newly developed algorithm was introduced to obtain detailed information of the impact of high glucose on AP profile. Compared to Ctrl, hyperglycemia in STZ-treated animals was coupled with prolongation of the QT interval, enhanced temporal dispersion of electrical recovery, and susceptibility to ventricular arrhythmias, defects observed, in part, in the Akita mutant mouse model of type I diabetes. AP was prolonged and beat-to-beat variability of repolarization was enhanced in diabetic myocytes, with respect to Ctrl cells. Density of Kv K(+) and L-type Ca(2+) currents were decreased in STZ myocytes, in comparison to cells from normoglycemic mice. Pharmacological reduction of Kv currents in Ctrl cells lengthened AP duration and increased temporal dispersion of repolarization, reiterating features identified in diabetic myocytes. CONCLUSIONS: Reductions in the repolarizing K(+) currents may contribute to electrical disturbances of the diabetic heart.