Jacopo Gianetti

Monitoring of monocyte functional state after extracorporeal circulation: a flow cytometry study.

Cardiovascular surgery with cardiopulmonary bypass (CPB) induces systemic inflammation and postoperative complications depending on pro‐ and anti‐inflammatory mechanisms. Activated polymorphonuclear cells and monocytes may be responsible for morbidity associated with CPB. Knowledge of the monocyte functional state in particular may help to develop protective interventions.

Biological features (inflammation and neoangiogenesis) and atherosclerotic risk factors in carotid plaques and calcified aortic valve stenosis: two different sites of the same disease?

Neoangiogenesis and inflammation have a pivotal role in atherosclerosis. Observations support the hypothesis that calcified aortic valve stenosis is an inflammatory process, similar to atherosclerosis in tissue features and risk factors. We studied 2 groups of cases: 47 were affected by hemodynamic atherosclerotic carotid plaque (group 1) and 35 by severe calcified aortic valve stenosis (group 2). We compared the groups for atherosclerosis risk factors, morphologic features, and immunohistochemical phenotypes. In both groups, men, smokers, and hypertensive subjects prevailed, and histologic analysis showed an elevated score for T-lymphocyte infiltrates, neoangiogenesis, calcium, and sclerosis. Adhesion molecule expression was present in both lesions. Expression of intercellular adhesion molecule 1 correlated with inflammatory infiltrates (group 1, P = .0007; group 2, P = .06). Neoangiogenesis also correlated with inflammatory infiltrates (group 1, P = .035; group 2, P = .045). In valves, neoangiogenesis correlated with calcium (P = .048). Carotid plaque and calcified valve stenosis showed common risk factors and biologic hallmarks of a chronic inflammatory process. Inflammation and neoangiogenesis have a crucial role in plaque evolution and in the progression of aortic valve stenosis.

Relationships Between Optical Aggregometry (Type Born) and Flow Cytometry in Evaluating ADP-Induced Platelet Activation

Platelet response to activating agents is used to monitor the efficacy of anti‐aggregation therapies. The aim of our study has been to demonstrate the existence of relationships between early events of ADP‐induced platelet activation, measured by flow cytometry and platelet‐rich plasma aggregation, quantified by optical aggregometry.

Correlation between inflammatory response and markers of neuronal damage in coronary revascularization with and without cardiopulmonary bypass

Off-pump coronary artery bypass graft (CABG) surgery may reduce the inflammatory response and the neuronal damage associated with conventional CABG on cardio-pulmonary bypass. The purpose of this study was to explore the protective effect of off-pump surgery by assessing plasma inflammatory and neuronal injury markers. Forty-one patients with coronary artery disease undergoing elective CABG were examined: 21 on-pump (Group I) and 20 off-pump (Group II). The perioperative release of interleukin-2 receptor (IL-2r), IL-6, tumor necrosis factor-alpha, S-100 protein (S-100) and neuron-specific enolase (NSE) were measured. Postoperative peak values of NSE (p B /0.001) and S-100 (p B /0.05) were significantly lower in Group II. IL-6 showed significantly lower values in off-pump patients (p B /0.001). A significant correlation was found between NSE and IL-6 (p B /0.001). In conclusion, off-pump surgery reduces the inflammatory response as well as the perioperative release of neuronal damage markers. Correlation between inflammatory activation and neuronal markers may suggest a link between inflammation and release of markers of neuronal clinical and subclinical injury.

Mitral valve repair for degenerative disease: is pericardial posterior annuloplasty a durable option?

OBJECTIVE Biological and prosthetic rings are available for supporting mitral valve repair (MVR). Contrasting data are reported on the durability of pericardial ring annuloplasty. This retrospective study was undertaken to assess the durability of MVR for degenerative regurgitation with posterior annuloplasty performed with glutaraldehyde-treated autologous pericardium. METHODS From August 1995 through December 2000, 133 patients underwent mitral repair for degenerative regurgitation (86 men, age 62.9+/-11.5 years). Thirty patients (22.6%) underwent combined coronary artery bypass graft and fourteen (10.5%) underwent tricuspid annuloplasty. Associated aortic disease, previous cardiac surgery and endocarditis were considered exclusion criteria. RESULTS Seventy-seven patients (57.9%) received a Carpentier-Edwards ring and 56 received (42.1%) an autologous pericardium ring. Thirty-day mortality was 3.8%. Mean follow-up, 98.3% complete, was of 35.6+/-18.7 months. Five-year freedom from reoperation and recurrence of mitral regurgitation> or =3+/4+ was significantly higher in the prosthetic ring group (90.1% - CL90%: 81.9-98.3%) compared with the pericardial ring group (62.6% - CL90%: 43.1-82.1%; P=0.027). Prosthetic ring implantation (P=0.004; RR=0.11) and preoperative New York Heart Association (NYHA) class< or =II (P=0.011; RR=0.16) were independently related to a lower risk of reoperation and recurrence of mitral regurgitation> or =3+/4+, by multivariate analysis. Five-year overall survival was 91.4% (CL90%: 87.9.7-95%). A higher preoperative left ventricular end-diastolic diameter (P=0.006; RR=1.17) and the severity of associated coronary artery disease (P=0.021; RR=2.00) were independent predictive factors for poor survival by multivariate analysis. CONCLUSIONS Posterior pericardial annuloplasty can jeopardize reproducibility and durability of MVR for degenerative regurgitation.

Pantoprazole significantly interferes with antiplatelet effect of clopidogrel: Results of a pilot randomized trial

BACKGROUND The CYP2C19*2 polymorphism is significantly associated with residual platelet reactivity (RPR) and maybe a major confounding factor in studies evaluating pharmacological interactions with clopidogrel. OBJECTIVES We sought to evaluate the influence of a proton pump inhibitor (PPI), pantoprazole, indicated as relatively less influent than other PPIs, on the antiplatelet effect of clopidogrel, considering a stratification of the population for the presence of cytochrome 2C19*2 polymorphism. METHODS 105 patients with ST elevation myocardial infarction (STEMI), treated with percutaneous coronary angioplasty (PCI) and who received dual antiplatelet therapy, were randomized between pantoprazole (n=54) or ranitidine (n=51). RPR was evaluated by Platelet Function Analyzer-100 (PFA-100) with collagen-epinephrine (CEPI) and collagene-ADP (CADP) cartridges and by light transmitted aggregometry with 10 μM adenosin diphosphate (ADP) and 1mM arachidonic acid (AA), on 5 (T0) and 30 (T1) days after PCI. RESULTS Demographic, clinical and procedural data and the prevalence of CYP2C19*2 polymorphism were similar between the two groups. Not statistically differences were observed for CEPI-CT and for the maximal aggregation (MA) values with AA stimulus at both times. We observed a significant increase in MA values with ADP in PPI group at T0 (p=0.01) and T1 (p=0.03). At the multiple regression analysis PPI use remained significantly associated with ADP-MA both at T0 (p=0.05) and T1 (p=0.03). CONCLUSIONS This is the first documentation in a randomized trial, after correction for the bias of CYP2C19*2 polymorphism, that pantoprazole increases the ADP-MA in patients treated with dual antiplatelet therapy.

Post-reperfusion changes of monocyte function in coronary blood after extracorporeal circulation.

Neutrophil and mononuclear cell functional changes represent a hallmark of inflammation during cardiopulmonary bypass and cardiovascular surgery. Knowledge of mechanisms underlying monocyte functional modulation in coronary blood may be useful to develop protective interventions that can limit ischemia/reperfusion injury.

Aortic valve disease with severe ventricular dysfunction: Stentless valve for better recovery

BACKGROUND Stentless bioprostheses and homografts show better hemodynamic profiles compared with conventional stented bioprostheses and mechanical valves. Few data are available on stentless aortic valve implantation for patients with severe left ventricular dysfunction. The aim of this retrospective study was to assess the potential benefits of stentless aortic valve implantation for patients undergoing isolated aortic valve replacement with left ventricular ejection fraction < or = 35%. METHODS From November 1988 through March 2000, 53 patients (45 men and 8 women, aged 64.2 +/- 15.2 years) with a LVEF < or = 35% (mean EF, 28.7 +/- 5.4%) underwent isolated, primary aortic valve replacement for chronic aortic valve disease. Twenty patients received stentless aortic valves and 33 patients received conventional stented bioprostheses and mechanical valves. Predictive factors for LVEF recovery at echocardiographic follow-up (36.2 +/- 32.1 months) were analyzed by simple and multiple regression analysis. RESULTS There were no significant differences between groups in early and late mortality. Stentless aortic valve implantation required a longer aortic cross-clamp time (p = 0.037). The stentless aortic valve group showed a better LVEF recovery (p = 0.016). Stentless aortic valves had a larger indexed effective orifice area compared with conventional stented bioprostheses and mechanical valves (p < 0.0001). A smaller indexed effective orifice area (p = 0.0008), chronic obstructive pulmonary disease (p = 0.015), and implantation of a conventional stented bioprosthesis or mechanical valve (p = 0.016) were related to reduced LVEF recovery by univariate analysis. A larger indexed effective orifice area (p = 0.024) was an independent predictive factor for a better LVEF recovery by multivariate analysis. CONCLUSIONS Stentless aortic valve implantation for patients with severe left ventricular dysfunction, even if technically more demanding, is a safe procedure that warrants a larger indexed effective orifice area leading to an enhanced LVEF recovery.

Risk Stratification After Coronary Artery Bypass Surgery by a Point-of-Care Test of Platelet Function

BACKGROUND Aspirin is one of the main therapeutics in prevention of cardiovascular events due to its antiplatelet activity. However, a sufficient inhibition of platelet function by aspirin is not always achieved. This means that the extent of protection from cardiovascular event is limited. Recently, several studies have introduced the concept of residual platelet reactivity during aspirin therapy and suggested that about 40% of aspirin users may not respond adequately. We sought to determine whether the profile and prevalence of residual platelet reactivity, measured with the platelet function analyzer (PFA-100; Dade/Behring, Marburg, Germany) device could predict a recurrent cardiovascular event in patients undergoing coronary artery bypass surgery. METHODS A cohort of 202 consecutive patients receiving primary coronary artery bypass surgery during 2004 was prospectively recruited. All patients postoperatively received regular standard daily 100 mg aspirin. Platelet function was analyzed by the PFA-100 at 30 +/- 6 days after surgery. A PFA100 closure time less than 190 seconds was defined as residual platelet reactivity. Eighty-six patients (43%) showed residual platelet reactivity. The mean follow-up time was 32 +/- 10 months and was 100% complete. RESULTS A total of 75 cardiovascular events have been registered. The majority of these events were among patients with residual platelet activity (p = 0.001). Out of this number, graft failure was documented in 25 patients. The 42-month freedom from major cardiovascular events was significantly better for patients with adequate platelet inhibition (p = 0.001). At multivariable analysis residual platelet reactivity (p = 0.012), incomplete revascularization (p = 0.029), and diabetes (p = 0.0009) were independently associated with occurrence of negative events. CONCLUSIONS Our results demonstrate that high residual platelet reactivity independently correlates with a worst clinical outcome in patients treated by coronary artery bypass surgery. The PFA-100 point care test could cheaply and simply discover this condition and contribute to improve the outcome of this subset of patients.

Granulocyte- and Monocyte-Platelet Adhesion Index in Coronary and Peripheral Blood After Extracorporeal Circulation and Reperfusion

Neutrophil‐granulocyte and mononuclear‐cell functional changes occur during cardiopulmonary bypass and cardiovascular surgery. In particular, leukocyte–platelet interaction, leading to generation of heterotypic coaggregates, represents an amplification mechanism of the local inflammatory response and tissue damage.