The Role of Protein Z and Protein Z-Dependent Protease Inhibitor Polymorphisms in the Development of Prosthetic Heart Valve Thrombosis.

BACKGROUND AND AIM OF THE STUDY: Protein Z (PZ) is a vitamin K-dependent factor that is synthesized mainly by the liver. It acts as an activator of serpin, the protein Z-dependent inhibitor (ZPI), which inhibits factor Xa. The potential role of alterations in protein Z and/or ZPI levels in the pathogenesis of thrombotic and/or hemorrhagic diseases has been previously investigated, but results have been conflicting. The study aim was to evaluate the role of PZ/ZPI polymorphisms in the development of prosthetic valve thrombosis (PVT). METHODS: This prospective, observational cross-sectional study included 50 consecutive patients with PVT [non-obstructive thrombosis (NOT) in 35 patients; obstructive thrombosis (OT) in 15] and 50 consecutive healthy subjects with normally functioning prostheses. gDNA was extracted from ca. 5 × 106 leukocytes, using the QIAamp DNA Mini Kit (Qiagen), according to the manufacturer's recommendations. For mutational analysis, a minisequencing method was employed. Results of the analyses were compared between the PVT and control groups, and also between the OT and NOT subgroups. RESULTS: The frequency of A allele (mutant type) of PZG79A was equal in all PVT patients and in controls. With regards to PZ-A13G polymorphisms, frequency of the mutant G allele was 22% in PVT patients and 19% in controls. Serpina-R67X polymorphism was observed in 8% of PVT patients and 6% of controls. Normal variant CC was present in 47 controls (94%), whereas a heterozygotic mutation (CT) was detected in four PVT patients (8%). Frequency of the ZPI-R67X mutation was significantly higher in patients with OT than in those with NOT (p = 0.041). CONCLUSIONS: The present study was the first to evaluate the potential impact of PZ (PZ-A13G, PZG79A) and ZPI (R-67X, W303X) polymorphisms in the development of PVT. Based on the results of this small observational case-control study, PZ/ZPI polymorphisms do not appear to play an active role in the development of PVT. Hence, further extensive studies are necessary.

Evaluation of Aortic Paravalvular Leak: A Special Reference for Anatomical Localization.

BACKGROUND AND AIM OF THE STUDY: Paravalvular leakage (PVL) remains an unavoidable complication of heart valve surgery and in its severe forms may lead to heart failure and hemolysis. The study aim was to evaluate the echocardiographic, clinical, surgical and laboratory characteristics of patients with aortic PVL. METHODS: A total of 77 aortic PVL patients underwent transthoracic and transesophageal echocardiography examinations. Clinical, echocardiographical and surgical findings were also recorded. RESULTS: Among the 77 patients, 21 (27.3%) had mild, 33 (42.8%) had moderate and 23 (29.9%) had severe aortic PVL. Seventeen patients (22.1%) had moderate-to-severe hemolysis and had a higher incidence of multiple PVL compared to those with no or mild hemolysis. Moderate- to-severe PVL was more frequent between the non-coronary and the left coronary sinus annuli, especially adjacent to the left main coronary artery ostium. Percutaneous closure was performed in five patients. Eleven patients underwent surgical repair, and the localizations of PVL were in accordance with echocardiographic findings. CONCLUSIONS: Aortic PVL occurs more frequently between the non-coronary sinus and the left coronary sinus annuli, which may be associated with multiple factors. Difficulties in seating the prosthesis due to the steep angulation of the commissure and annulus, the avoidance of deep sutures, and focal annular calcification may make this region prone to injury and leakage.