Anesthesiological Management in Transcatheter Mitral Valve Repair With MitraClip: Beyond the EVEREST Criteria.

Percutaneous mitral valve repair with the MitraClip system recently emerged as a viable and less invasive therapeutic option in patients with severe mitral regurgitation deemed to be high-risk surgical candidates. Mitral valve morphology and geometry features are key elements for MitraClip eligibility. In the setting of functional mitral regurgitation, the presence of a leaflet coaptation gap due to advanced left ventricle remodeling can be a potential exclusion criterion for MitraClip therapy. In this article, the authors present a case of successful MitraClip implantation in a patient with severe functional mitral regurgitation and a significant coaptation gap. Periprocedural and intraoperative pharmacological and anesthesiological management were fundamental for successful grasping and procedural success.

Antiplatelet Therapy for Non-ST-Segment Elevation Myocardial Infarction in Complex "Real" Clinical Scenarios: A Consensus Document of the "Campania NSTEMI Study Group".

The incidence of ST-segment elevation myocardial infarction (STEMI) has significantly decreased. Conversely, the rate of non-STEMI (NSTEMI) has increased. Patients with NSTEMI have lower short-term mortality compared to patients with STEMI, whereas at long-term follow-up, the mortality becomes comparable. This might be due to the differences in baseline characteristics, including older age and a greater prevalence of comorbidities in the NSTEMI population. Although antithrombotic strategies used in patients with NSTEMI have been well studied in clinical trials and updated guidelines are available, patterns of use and outcomes in clinical practice are less well described. Thus, a panel of Italian cardiology experts assembled under the auspices of the "Campania NSTEMI Study Group" for comprehensive discussion and consensus development to provide practical recommendations, for both clinical and interventional cardiologists, regarding optimal management of antithrombotic therapy in patients with NSTEMI. This position article presents and discusses various clinical scenarios in patients with NSTEMI or unstable angina, including special subsets (eg, patients aged ≥85 years, patients with chronic renal disease or previous cerebrovascular events, and patients requiring triple therapy or long-term antithrombotic therapy), with the panel recommendations being provided for each scenario.

[Lotus Sadra valve implantation complicated by type B aortic dissection: diagnosis and treatment]. / Impianto di Lotus Sadra complicato da dissezione aortica di tipo B: diagnosi e trattamento.

Transcatheter aortic valve implantation (TAVI) is a validated technique for the treatment of aortic valve stenosis in patients with high surgical risk or inoperable. We present the case of an 80-year-old woman with severe aortic valve stenosis (mean gradient 55 mmHg), mild surgical risk, who refused traditional surgery. We implanted a Lotus Sadra 25 mm (Boston Scientific, Marlborough, MA, USA) via the transfemoral route. During pull back delivery, the patient experienced interscapular pain with angiographic evidence of type B aortic dissection effectively treated by implanting a vascular endoprosthesis Valiant 30 x 150 mm (Medtronic Vascular, Santa Rosa, CA, USA). Type B aortic dissection is a rare event during TAVI. The onset of procedural complications, often unpredictable, suggests the need for more extensive knowledge of materials and techniques, in particular with respect to endovascular treatment of the aortic and iliac-femoral district.

Bioabsorbable drug-eluting vascular scaffold for the treatment of coronary in-stent restenosis: A two center registry.

BACKGROUND/PURPOSE: Coronary in-stent restenosis (ISR) is a clinical problem for which a satisfactory solution has not been found yet. Bioabsorbable drug eluting vascular scaffolds (BVSs) provide transient vessel scaffolding combined with prolonged drug delivery capability. The aim of this study was to investigate the safety of BVS for the treatment of coronary ISR. METHODS/MATERIALS: Between January 2013 and June 2013, 27 patients (31 lesions), presenting with either stable or unstable angina due to coronary ISR, were enrolled in a single arm, prospective, open label registry. Primary end point was the occurrence of target vessel revascularization (TVR) at 12 months. Secondary end point was the composite of death, myocardial infarction and TVR at 12 months. RESULTS: A diffuse ISR pattern was present in 70% of the lesions; mean lesion length was 34.6±15. BVS was successfully implanted in all patients with no in hospital MACE. At twelve months of follow up, MACE rate was 18.5%. One patient died for non-cardiac reason, one patient died due to a possible stent thrombosis and TVR was necessary in 3 patients (11.1%). CONCLUSIONS: Our data suggest that BVS is safe and technically feasible for treatment of long and diffuse coronary ISR. These data could be considered hypothesis generator for a randomized clinical trial.

Role for the Kunitz-3 domain of tissue factor pathway inhibitor-alpha in cell surface binding.

BACKGROUND: Tissue factor pathway inhibitor (TFPI)-alpha, a key regulator of tissue factor-induced coagulation, contains 3 tandem Kunitz-type inhibitory domains. Kunitz-1 binds and inhibits factor VIIa in the factor VIIa/tissue factor complex, and Kunitz-2 binds and inhibits factor Xa. The role of the Kunitz-3 domain of TFPI-alpha, however, has remained an enigma. METHODS AND RESULTS: To determine the structures within TFPI-alpha involved in its binding to cell surface, altered forms of TFPI-alpha were expressed in C127 (mouse mammary) cells: C-terminal truncated forms TFPI-alpha (252), TFPI-alpha (242), and TFPI-alpha (181), which also lacks the third Kunitz domain (K3); TFPI-alpha (desK3), which lacks only the K3 domain; and TFPI-alpha (R199L), in which the putative P1 site in K3 is changed from arginine to leucine. By flow cytometry (fluorescence-activated cell sorting), the altered forms 252, 242, and R199L showed significantly reduced binding, whereas the forms 181 and desK3 completely failed to bind to the cell surface. Transient expression of WT-, desK3-, and K3/K2-TFPI-alpha (in which K3 is replaced with K2) in another cell line (b-end3, mouse endothelial) produced comparable results. Exogenously added C-terminal truncated and R199L forms of TFPI-alpha bound poorly and desK3 did not bind at all to the surface of ECV304 cells in which TFPI-alpha expression had been "knocked down" by RNA interference. CONCLUSIONS: Optimal cell binding of endogenously expressed TFPI-alpha requires its K3 and C-terminal domains, and within the K3 domain, the P1 (R199) residue plays an important role. Thus, one role of the K3 domain involves the cell surface localization of TFPI-alpha.

Involvement of tissue factor pathway inhibitor in the coronary circulation of patients with acute coronary syndromes.

BACKGROUND: Tissue factor pathway inhibitor (TFPI) is the endogenous inhibitor of the extrinsic coagulation pathway; however, its involvement during thrombus formation in patients with acute coronary syndromes (ACS) is still unknown. METHODS AND RESULTS: Transcardiac (aorta/coronary sinus) free and total TFPI (free + lipoprotein-bound form) levels, as well as TFPI/factor Xa (FXa) complex levels, were measured in plasma samples obtained from patients with acute myocardial infarction undergoing primary PTCA and patients with unstable angina undergoing urgent PTCA. Patients with stable angina undergoing elective PTCA served as controls. In addition, prothrombin fragment 1+2 and fibrinopeptide A plasma levels were measured. Samples were collected at baseline, after PTCA, and after stent deployment. In patients with ACS, both total and free TFPI plasma levels in the coronary sinus were significantly lower than the corresponding levels measured in the aorta at any time point of the study; conversely, a significant increase in TFPI/FXa complex plasma levels was observed in the coronary sinus as compared with the aorta. In contrast, in patients with stable angina, no differences were observed in TFPI and TFPI/FXa levels at baseline in the coronary sinus as compared with the aorta. CONCLUSIONS: TFPI is involved in the process of thrombus formation in vivo in patients with ACS, which suggests a potential role for TFPI in modulating coronary thrombosis.

Glycosyl phosphatidylinositol anchorage of tissue factor pathway inhibitor.

BACKGROUND: The endothelium is a major source of tissue factor pathway inhibitor (TFPI), the endogenous regulator of TF-induced coagulation, and a significant proportion of the expressed TFPI remains associated with the endothelial surface. METHODS AND RESULTS: Phosphatidylinositol-specific phospholipase C (PI-PLC) treatment reduced TFPI at the surface of cultured endothelial cells by approximately 80%, and at least a portion of the TFPI released by PI-PLC contained an intrinsic glycosylphosphatidylinositol (GPI) anchor that is recognized by anti-crossreactive determinant antibodies. Endothelial cells express both of the alternatively spliced forms of TFPI mRNA at a ratio of TFPIbeta/TFPIalpha mRNA of approximately 0.1 to 0.2. In Chinese hamster ovary (CHO) cells, TFPIalpha is predominantly secreted, whereas TFPIbeta is a GPI-anchored membrane protein. Like TFPIbeta, the small proportion of the TFPIalpha expressed by CHO cells that remains surface associated is also released by PI-PLC treatment, suggesting that it is bound to a separate GPI-anchored protein(s) at the surface of the cells. CONCLUSIONS: Both direct (TFPIbeta) and indirect (TFPIalpha) GPI-mediated membrane anchorage is involved in localizing TFPI to the surface of cells.

Induction of tissue factor in the arterial wall during recurrent thrombus formation.

OBJECTIVE: Tissue factor (TF) is normally expressed at low levels in the media of blood vessels, but it is readily induced after vessel injury. It is not known whether vascular damage per se or thrombus formation is responsible for this phenomenon. METHODS AND RESULTS: Cyclic flow variations (CFVs), attributable to recurrent thrombus formation, were induced in stenotic rabbit carotid arteries with endothelial injury. CFVs were observed for 30 minutes and 2, 4, and 8 hours in different groups of animals. Another group of rabbits pretreated with hirudin before inducing arterial damage to inhibit thrombus formation was observed for 8 hours. Arterial sections were immunostained for TF. Undamaged arteries served as controls. In additional rabbits, in situ hybridization experiments were performed. No TF expression was observed in the media of control vessels, whereas a progressive increase in TF mRNA and protein expression was observed in carotid arteries as CFVs progressed. No increase in TF expression was observed in animals pretreated with hirudin. In vitro experiments demonstrated that TF mRNA is induced in smooth muscle cells stimulated with activated platelets as well as with some platelet-derived mediators. CONCLUSIONS: This phenomenon may contribute to sustain intravascular thrombus formation after the initial thrombogenic stimulus.

Activated platelets stimulate tissue factor expression in smooth muscle cells.

UNLABELLED: Tissue factor (TF)-induced activation of the coagulation plays a key role in the pathophysiology of acute coronary syndromes. Because TF represents the initial trigger of the coagulation cascade, its expression in the arterial wall is tightly regulated. OBJECTIVE: To determine whether and which soluble mediators released during platelet activation may upregulate TF expression in smooth muscle cells (SMCs). METHODS AND RESULTS: Rabbit SMCs were challenged with collagen-activated platelets and their effects on TF mRNA transcription and protein expression were evaluated at different time points (30 min, 1, 2, 4, 8, 12 and 24 h) by RT-PCR, immunofluorescence and a two-stage colorimetric assay. A progressive increase in TF mRNA, peaking at 2 h, was evident in SMCs stimulated with activated platelets with respect to baseline. The increase in TF mRNA expression was associated with a parallel increase in TF protein, as demonstrated by immunofluorescence and by colorimetric assay. In a different set of experiments, selected platelet-derived soluble mediators were shown to induce TF mRNA expression. CONCLUSIONS: Activated platelets upregulate TF, via release of several soluble mediators, in a cell population widely expressed in the vessel wall and in atherosclerotic plaques, such as SMCs. This phenomenon might play an important role in sustaining thrombus formation in vivo.