Giovanni Paolini

Oral L-arginine supplementation improves endothelial function and ameliorates insulin sensitivity and inflammation in cardiopathic nondiabetic patients after an aortocoronary bypass

It is known that L-arginine treatment can ameliorate endothelial dysfunction and insulin sensitivity in type 2 diabetes mellitus patients, but little is known on L-arginine effects on these variables in nondiabetic patients with stable cardiovascular disease (coronary artery disease). We evaluated the effects of long-term oral L-arginine treatment on endothelial dysfunction, inflammation, adipokine levels, glucose tolerance, and insulin sensitivity in these patients. Sixty-four patients with cardiovascular disease previously submitted to an aortocoronary bypass and not known for type 2 diabetes mellitus had an oral glucose load to define their glucose tolerance. Thirty-two patients with nondiabetic response were eligible to receive, in a double-blind randomized parallel order, L-arginine (6.4 g/d) or placebo for 6 months. An evaluation of insulin sensitivity index during the oral glucose load, markers of systemic nitric oxide bioavailability and inflammation, and blood flow was performed before and at the end of the treatment in both groups. Compared with placebo, L-arginine decreased asymmetric dimethylarginine levels (P < .01), indices of endothelial dysfunction, and increased cyclic guanosine monophosphate (P < .01), L-arginine to asymmetric dimethylarginine ratio (P < .0001), and reactive hyperemia (P < .05). Finally, L-arginine increased insulin sensitivity index (P < .05) and adiponectin (P < .01) and decreased interleukin-6 and monocyte chemoattractant protein-1 levels. In conclusion, insulin resistance, endothelial dysfunction, and inflammation are important cardiovascular risk factors in coronary artery disease patients; and L-arginine seems to have anti-inflammatory and metabolic advantages in these patients.

Extracorporeal membrane oxygenation to support adult patients with cardiac failure: predictive factors of 30-day mortality

Adult patients supported on extracorporeal membrane oxygenation (ECMO) are very sick and many complications are often present in each single patient; therefore, it is not always easy to find some risk factors that can predict the early outcome. This retrospective study reports our experience in ECMO support treatment in adult cardiac patients suffering from cardiac failure (CF) in which one or more predictive factors of 30-day mortality were analyzed. Between January 2002 and August 2009, 42 consecutive adult cardiac patients with cardiogenic shock (mean age 64.3+/-11.3 years) were supported on ECMO for >2 days. They were divided into patients who had a survival <30 days (n=20) and patients who survived >30 days (n=22). Twenty-nine patients (69%) survived on ECMO. Sixteen patients were discharged with a survival rate of 38.1%. The overall mean ECMO duration was 7.9+/-5.3 days. The following variables were significantly different between the two groups: number of platelets and packed red blood cells (PRBCs) transfused per day during ECMO (P=0.002 and P=0.003), blood lactate levels 48 h and 72 h after the initiation of ECMO (P=0.01 and P=0.04), indexed blood flow after 48 h and 72 h (P=0.01 and P<0.0001), liver failure (P=0.001) and multiorgan failure (P=0.002). Stepwise logistic regression identified that blood lactate levels at 48 h and number of PRBCs transfused were associated with 30-day mortality [P=0.019, odds ratio (OR) =2.16; 95% confidence interval (CI)=1.13-4.14 and P=0.008, OR=1.08; 95% CI=1.02-1.14, respectively]. The predicted probability of mortality would be 52% when blood lactate levels are >3 mmol/l after 48 h. The blood lactate level at 48 h and PRBCs transfused per day can be considered as important parameters to predict the mortality in adult cardiac patients supported by ECMO for CF.

Relation between left ventricular function and oxidative stress in patients undergoing bypass surgery

Objective To determine whether preoperative left ventricular ejection fraction (LVEF) is related to the degree of myocardial oxidative stress during bypass surgery in man. Design Observational study. Setting Tertiary care centre. Patients and interventions 31 patients (LVEF range was 20% to 68%) undergoing elective coronary bypass surgery with blood cardioplegic reperfusion were studied. Arterial and coronary sinus blood was collected before aortic cross clamping (T0) and at 0 (T1), 15 (T2), and 30 (T3) minutes after unclamping. Transmural left ventricular biopsies were also obtained from 15 patients at T0 and at T1. Main outcome measures Glutathione and adenine nucleotides were measured in myocardial biopsies, while coronary sinus–artery differences for glutathione, nucleotides, and products of lipid peroxidation were calculated from blood specimens. Creatine kinase (myocardial band; CK-MB) was measured in plasma at four and 12 hours after operation. Results Myocardial glutathione and adenine nucleotides were correlated (pu2009<u20090.02) with preoperative LVEF both at T0 (ru2009=u20090.909 and 0.672) and T1 (ru2009=u20090.603 and 0.605). Oxidised glutathione released from the heart during reperfusion was inversely correlated with LVEF (ru2009=u2009−0.448, −0.466, and −0461 at T1, T2, and T3, pu2009<u20090.01), while reduced glutathione (ru2009=u20090.519 and 0.640 at T1 and T2) and glutathione redox ratio (ru2009=u20090.647, 0.714, 0.645, and 0.702 at T0, T1, T2, and T3) showed a direct correlation (pu2009<u20090.01). Lipid peroxidation at T1 was negatively related to LVEF (ru2009=u2009−0.492). CK-MB was also negatively related to LVEF (ru2009=u2009−0.440 at 4 h and −0.462 at 12 h). Conclusions The capacity to counterbalance oxidative burst following ischaemia and reperfusion appears to be related to the functional ability of the heart.

The Italian study of the Mitroflow postoperative results (ISTHMUS): a 20-year, multicenter evaluation of Mitroflow pericardial bioprosthesis

OBJECTIVEnA multicentre experience with the Mitroflow pericardial bioprosthesis has been evaluated longitudinally over a 20-year period.nnnMETHODSnFrom 1988 through 2008, 1591 patients (mean age, 75.3±6.8 years, and 60.1% female) from 12 centres had a Mitroflow in the aortic position. Concomitant coronary artery bypass was performed in 41.9% (n=666) of patients, urgency/emergency surgery in 9.5% (n=152) and replacement of degenerated prosthesis in 2.3% (n=36). Follow-up (7.447 patient-years) was 99.2% complete. Median follow-up was 61.9 months (interquartile range (IQR) 30.8-90.9 months). The study was carried out following American Association for Thoracic Surgery/Society for Thoracic Surgeons/European Association for Cardio-Thoracic Surgery (AATS/STS/EACTS) Guidelines for reporting valve morbidity and mortality.nnnRESULTSnThe early (30-day) mortality was 6.5% (n=104). Actuarial survival rates at 10, 15 and 18 years were 53%, 34% and 27%, respectively (2.2 patient/year). Re-operation was required in 96 patients (5.9%), of whom 59 patients (3.7%) for structural valve degeneration. Actuarial freedom from prosthetic valve degeneration at 18 years was 65.5% (78% in patients>70 years) with a linearised rate of 1.4 patient/year (0.8 patient/year in patients>70 years). At 18 years, freedom from embolism was 82% (0.9 patient/year), freedom from valve endocarditis was 89% (0.6 patient/year) and freedom from bleeding episodes was 95% (0.2 patient/year), respectively.nnnCONCLUSIONSnThis independent multicentre study indicates that the Mitroflow pericardial bioprosthesis provides favourable long-term postoperative results with a low rate of valve-related events and need of re-intervention, particularly in patients older than 70 years.

Myocardial revascularization with miniaturized extracorporeal circulation versus off pump: Evaluation of systemic and myocardial inflammatory response in a prospective randomized study.

OBJECTIVEnThis prospective randomized study sought to verify the systemic inflammatory response, inflammatory myocardial damage, and early clinical outcome in coronary surgery with the miniaturized extracorporeal circulation system or on the beating heart.nnnMETHODSnSixty consecutive patients were randomized to miniaturized extracorporeal circulation (n = 30) or off-pump coronary revascularization (off-pump coronary artery bypass grafting, n = 30). Intraoperative and postoperative data were recorded. Plasma levels of interleukin-6 and tumor necrosis factor-alpha were measured from systemic blood intraoperatively, at the end of operation, and 24 and 48 hours thereafter. Levels of the same markers and blood lactate were measured from coronary sinus blood intraoperatively to evaluate myocardial inflammation. Markers of myocardial damage were also analyzed.nnnRESULTSnOne patient died in the off-pump coronary artery bypass grafting group. There was no statistical difference in early clinical outcome in both groups. Release of interleukin-6 was higher in the off-pump coronary artery bypass grafting group 24 hours after the operation (P = .03), whereas levels of tumor necrosis factor-alpha were not different in both groups. Cardiac release of interleukin-6, tumor necrosis factor-alpha, and blood lactate were not different in both groups. Release of troponin T was not significantly different in both groups. Levels of creatine kinase mass were statistically higher in the miniaturized extracorporeal circulation group than in the off-pump coronary artery bypass grafting group, but only at the end of the operation (P < .0001). Hemoglobin levels were significantly higher in the miniaturized extracorporeal circulation group than in the off-pump coronary artery bypass grafting group after 24 hours (P = .01).nnnCONCLUSIONnMiniaturized extracorporeal circulation can be considered similar to off-pump surgery in terms of systemic inflammatory response, myocardial inflammation and damage, and early outcome.

Role of leucocytes in free radical production during myocardial revascularisation.

OBJECTIVE: To evaluate the role of leucocytes in free radical production in patients with depressed or normal ejection fraction undergoing coronary bypass. DESIGN: Two randomised control trials. SETTING: Tertiary care centre. PATIENTS AND INTERVENTIONS: In the first study, 22 patients with ejection fractions of < or = 40% received blood cardioplegic reperfusion with (n = 11) or without (n = 11) leucocyte depletion. In the second study, 22 patients with ejection fractions > or = 45% received either leucocyte depleted (n = 11) or blood cardioplegia (n = 11). MAIN OUTCOME MEASURES: Glutathione, hypoxanthine, and lipid peroxidation products were measured in coronary sinus blood and plasma before aortic cross clamping and at 0, 15, and 30 minutes after unclamping. Haemodynamic variables and creatine kinase MB isoenzymes were monitored on the first postoperative day. Comparison between treatments was performed on difference (delta) between measurements at time 0 and at baseline, and on slopes obtained by fitting measurements after unclamping with a linear regression model. RESULTS: At unclamping no difference in delta for plasma glutathione redox ratio (oxidised/total glutathione, %) was observed between treated and control groups with low ejection fraction (delta = 16 (SD 8.39) and 24 (7.0) redox ratio %, respectively). Baseline value recovery rate (redox ratio %/min) was significantly faster in treated v control patients (slope -0.912 (0.380) v -0.158 (0.200), P < 0.005, respectively). Cardiac index showed a trend to greater improvement in the treated group (slope 0.04 (0.03) v 0.003 (0.002) 1/min/m2/h, P < 0.02, treated v controls, respectively). In patients with normal ejection fraction, leucocyte depletion did not result in significant improvement v controls. CONCLUSIONS: Leucocyte depletion seems to provide benefit only in patients with left ventricular dysfunction.

St. Jude Medical Trifecta aortic valve: results from a prospective regional multicentre registry

BackgroundThe Trifecta aortic bioprosthesis (St. Jude Medical, Inc., St. Paul, MN, USA) is a stented pericardial heart valve with excellent preliminary results. Aim of the study was to evaluate its early clinical and hemodynamic performances in a multicenter regional registry.MethodsBetween January 2011 and June 2012, 178 consecutive patients undergoing aortic valve replacement with the Trifecta bioprosthesis were prospectively enrolled at 9 Italian centers. Clinical and echocardiographic data were collectedat discharge, 6-months and at 1-year postoperatively.ResultsThe average age was 75.4u2009±u20097.7xa0years,and 95 (53xa0%) were men. Indication for valve replacement included stenosis in 123 patients (69xa0%), mixed lesions in 25 (14xa0%), and regurgitation in 30 (17xa0%). Ninety-three (52xa0%) patients were in NYHA functional class III/ IV. Hospital mortality accounted for 5 (2.8xa0%) patients. No valve-related perioperative complications were encountered. Median follow-up was 20.5xa0months (range: 1-34). Early (≤6xa0months) complications included one thromboembolic event, one major bleeding, and 3 endocarditis (2 explants). Two late (>6xa0months) thromboembolic events and two endocarditis (1 explant) were registered. No valve thrombosis or structural deterioration were observed after discharge. At 30-months, freedom from all-cause mortality was 87xa0%, freedom from valve-related mortality 99.4xa0%, freedom from endocarditis 97.5xa0%, and freedom from valve explants 98xa0%. At 1-year, mean gradients ranged from 8 to 16xa0mmHg, and effective orifice area indexes from 1.0 to 1.2xa0cm2/m2 for valve sizes from 19 to27 mm, respectively. No patients had severe prosthesis-patient mismatch.ConclusionsTrifecta bioprosthesis provided favourable clinical and hemodynamic results over time.

Late driveline left ventricular assist device infection treated with frozen-and-thawed allogeneic platelet gel

In this case report, we report the application of frozen-and-thawed allogeneic platelet gel (PLT-gel) to treat a late driveline exit site infection in a 56-year old patient supported by a Heartware-HVAD left ventricular assist device. The treatment duration was 4 weeks and at the follow-up the skin around the exit site was free from further infection. PLT-gel can be used to treat local infection of the driveline exit site and to prevent further high-risk infections.

An unusual case of a cardiocutaneous fistula presenting 30 years after a breast carcinoma

A 77-year old woman presented with bleeding and purulent drainage from a cutaneous fistula appearing 30 years after left mastectomy and cobaltotherapy due to breast cancer, in the left anterior thoracic wall. A computed tomography scan showed a left ventricle connection (Figs 1 and 2). Surgical treatment was recommended, but she refused. After 4 months, she died in spite of an emergency operation following an haemorrhage.

Incidence of perioperative stroke in clampless aortic anastomosis during off-pump coronary artery bypass grafting

This study aimed to assess if clampless off-pump coronary artery bypass grafting (OPCAB) decreases the incidence of perioperative stroke (POS) rate and in-hospital mortality. The secondary aim was to evaluate 12-year rates of overall mortality. Between January 2003 to December 2015, data of 645 consecutive patients undergoing isolated CABG were retrospectively collected. 363 underwent aortic no-touch OPCAB (No-touch group) and 282 underwent OPCAB with the Heartstring device (HS group). In-hospital mortality and perioperative stroke rate as primary endpoint, as well as long-term follow-up outcome were analysed. In-hospital mortality was lower into No-touch group compared with HS group but without significant statistical difference (1.7 vs. 3.2%, pxa0=xa00.19, respectively); the rate of postoperative stroke was higher in No-touch group compared with HS group, although this difference did not reach statistically significance. Delirium was reported with higher presentation rate in HS group (3.9 vs. 0.8%, pxa0=xa00.01). Blood transfusions rate was higher in HS subjects (23.4 vs. 16.1%, pxa0=xa00.01). Intubation time, ICU, and hospital length of stay were increased in the HS group (pxa0=xa00.008, pxa0=xa00.001 and pxa0=xa00.003, respectively). Over a 12-year follow-up period, survival probabilities at 1, 5, and 10xa0years were 93.6xa0±xa01.3 vs. 93.2xa0±xa01.5, 80.4xa0±xa02.6 vs. 80.3xa0±xa02.2, and 57.9xa0±xa05 vs. 58.4xa0±xa03.8% in the No-touch and HS group, respectively (pxa0=xa00.97). In this retrospective study, clampless off-pump CABG lowers perioperative stroke rate whose incidence is, however, not inferior compared with No-touch technique, and no statistically significance was detected. Delirium has a higher presentation rate in clampless off-pump CABG.