Giovanni Coppi

Early and transient release of leukocyte pentraxin 3 during acute myocardial infarction.

Pentraxin 3 (PTX3) plays cardioprotective and anti-atherogenic roles in murine models. PTX3 blood levels raise during early acute myocardial infarction (AMI). Neutrophils from healthy subjects physiologically contain PTX3 in secondary (also called specific) granules. In this study, we report that circulating neutrophils release preformed PTX3 in the early phase of AMI (within 6 h from the onset of clinical symptoms). Depletion of intracellular PTX3 correlates with increased plasma levels and with platelet–neutrophil heterotypic aggregates. Neutrophil PTX3 returns to normal values 48 h after the onset of symptoms; concentration does not vary in matched healthy controls or in patients with chronic stable angina. In vitro, recognition of activated P-selectin+ platelets causes the formation of neutrophil–platelet heteroaggregates and the release of neutrophil PTX3. Purified or membrane-bound P-selectin triggers PTX3 release from resting neutrophils. Released PTX3 binds to activated platelets in vitro. Moreover, PTX3 binds to a substantial fraction of platelets from patients in the circulating blood. PTX3-bound activated platelets have a reduced ability to 1) form heterotypic aggregates with neutrophils and monocytes; 2) activate neutrophils, as evaluated assessing the upregulation of leukocyte β2 integrins; 3) aggregate with other platelets; and 4) bind to fibrinogen. Our results suggest that neutrophils early release prestored PTX3 in patients undergoing AMI. PTX3 binds to activated circulating platelets and dampens their proinflammatory and prothrombotic action, thus possibly contributing to its cardioprotective effects.

An Intense and Short-Lasting Burst of Neutrophil Activation Differentiates Early Acute Myocardial Infarction from Systemic Inflammatory Syndromes

Background Neutrophils are involved in thrombus formation. We investigated whether specific features of neutrophil activation characterize patients with acute coronary syndromes (ACS) compared to stable angina and to systemic inflammatory diseases. Methods and Findings The myeloperoxidase (MPO) content of circulating neutrophils was determined by flow cytometry in 330 subjects: 69 consecutive patients with acute coronary syndromes (ACS), 69 with chronic stable angina (CSA), 50 with inflammation due to either non-infectious (acute bone fracture), infectious (sepsis) or autoimmune diseases (small and large vessel systemic vasculitis, rheumatoid arthritis). Four patients have also been studied before and after sterile acute injury of the myocardium (septal alcoholization). One hundred thirty-eight healthy donors were studied in parallel. Neutrophils with normal MPO content were 96% in controls, >92% in patients undergoing septal alcoholization, 91% in CSA patients, but only 35 and 30% in unstable angina and AMI (STEMI and NSTEMI) patients, compared to 80%, 75% and 2% of patients with giant cell arteritis, acute bone fracture and severe sepsis. In addition, in 32/33 STEMI and 9/21 NSTEMI patients respectively, 20% and 12% of neutrophils had complete MPO depletion during the first 4 hours after the onset of symptoms, a feature not observed in any other group of patients. MPO depletion was associated with platelet activation, indicated by P-selectin expression, activation and transactivation of leukocyte β2-integrins and formation of platelet neutrophil and -monocyte aggregates. The injection of activated platelets in mice produced transient, P-selectin dependent, complete MPO depletion in about 50% of neutrophils. Conclusions ACS are characterized by intense neutrophil activation, like other systemic inflammatory syndromes. In the very early phase of acute myocardial infarction only a subpopulation of neutrophils is massively activated, possibly via platelet-P selectin interactions. This paroxysmal activation could contribute to occlusive thrombosis.

Diagnostic Laparoscopy for Early Detection of Acute Mesenteric Ischaemia in Patients with Aortic Dissection

INTRODUCTION Recognition of acute mesenteric ischaemia (AMesI) in patients with aortic dissection (AoD) may be a challenge and exploratory laparotomy is often performed. METHODS We retrospectively analysed our experience with the use of diagnostic laparoscopy (DL) for the early detection of AMesI in patients with AoD, either undergoing medical treatment or after open/endovascular interventions. RESULTS Between 2004 and 2011, 202 consecutive AoDs were treated in our centre (71 acute type A AoD; 131 acute and chronic type B AoD). Among the 17 (8.4%) patients in which AMesI was suspected, nine (52.9%) were selected for DL. Three DLs were performed during medical treatment of patients with acute type B AoD, six after treatment of AoD (both surgical and endovascular). Three second-look DLs were also performed. Eight DLs were negative, three showed AMesI and the patients underwent successful emergent revascularisation. One DL was not conclusive and laparotomy was required. Among the eight patients not submitted to DL, one case of bowel infarction was recorded. CONCLUSIONS In our series DL was feasible and safe. The low invasiveness and repeatability were the main advantages. Although additional experience is mandatory, DL seems a promising technique for the detection of AMesI in patients with AoD.

Comparison of renal perfusion solutions during thoracoabdominal aortic aneurysm repair

BACKGROUND To determine whether renal perfusion with cold crystalloid solution enriched with histidine-tryptophan-ketoglutarate (Custodiol; Dr Franz-Kohler Chemie GmbH, Bensheim, Germany) provides better protection against renal ischemic injury than cold lactated Ringers solution in patients undergoing thoracoabdominal aortic aneurysm open repair. METHODS We analyzed a prospectively compiled database containing all 111 consecutive patients who underwent thoracoabdominal aortic aneurysm open repair at our center from 2008 to 2011. A cohort of 104 consecutive patients was identified of which 50 (48%) had renal perfusion with Custodiol and 54 (52%) with lactated Ringers solution. Propensity score matching based on baseline clinical variables, which were expected to influence renal outcomes, was performed to correct for any bias that may have been associated with the use of Custodiol. Acute kidney injury (AKI) as defined by Kidney Disease Improving Global Outcomes guidelines and perioperative estimated glomerular filtration rate were compared in the two groups. Independent predictors of AKI were also identified by multivariate analysis. RESULTS After propensity score matching, we were able to match 42 Custodiol cases one-to-one with those receiving perfusion with lactated Ringers solution. Overall 30-day mortality was 5.9%; temporary hemodialysis or continuous veno-venous hemofiltration was needed in 4.8% of the patients without any case of dialysis at discharge. Freedom from AKI was significantly increased in the Custodiol group (38.1% vs 9.5%; P = .002) despite longer total renal ischemic time (51.5 ± 16.4 minutes vs 43.6 ± 16.0 minutes; P = .05). By analysis of variance for repeated measures, a significant upward trend of perioperative estimated glomerular filtration rate was observed in the Custodiol group (group × time interaction = F3,66; P < .001), and by multivariate analysis, Custodiol perfusion was the only independent predictor of non-AKI (P = .04). CONCLUSIONS The use of Custodiol was safe and provided improved perioperative renal function compared with lactated Ringers solution. Randomized trials are needed to confirm these data and to assess their clinical consequences.

Delayed open conversion after endovascular abdominal aortic aneurysm: device-specific surgical approach.

OBJECTIVES Despite several advances in endoluminal salvage for failed endovascular abdominal aortic repair (EVAR), in our experience an increasing number of cases necessitate delayed open conversion (dOC). METHODS EVAR patients requiring delayed (>30 days) conversion were prospectively collected in a computerized database including demographics, details of aortoiliac anatomy, procedural and clinical success, and postoperative complications. RESULTS Between 2005 and 2011, 54 patients were treated for aortic stent-graft explantation. Indications included 34 type I and III endoleaks, 13 type II endoleaks with aneurysm growth, 4 cases of material failures, and 3 stent-graft infections. All fit-for-surgery patients with type I/III endoleak underwent directly dOC. Different surgical approaches were used depending on the type of stent-graft. Overall 30-day mortality was 1.9%. Overall morbidity was 31% mainly due to acute renal failure (13 cases). Mean hospitalization was 6 days (range, 5-27 days). Overall survival at mean follow-up of 19 months was 78%. CONCLUSIONS In recent years, the use of EVAR has increased dramatically, including in young patients regardless of their fitness for open repair. dOC after endovascular abdominal aortic aneurysm seems to be a lifesaving procedure with satisfactory initial and mid-term results.

Urgent carotid artery stenting with technical modifications for patients with transient ischemic attacks and minor stroke.

Purpose To evaluate the safety and efficacy of urgent carotid artery stenting (CAS) with technical modifications in patients with recent (<24 hours) initial or recurrent (≥2 episodes in 24 hours) transient ischemic attacks (TIA) or with minor stroke. Methods A single-center, prospective, observational study was begun in March 2005 to assess an urgent CAS protocol for the treatment of selected high-risk patients with carotid artery disease who presented within 24 hours of an initial or recurrent TIA or minor stroke. Up to June 2011, 78 patients (59 men; mean age 76 years) with TIA (n=57) or minor stroke (n=21) underwent urgent CAS (within 48 hours) for severe internal carotid artery stenosis. Outcome measures were major adverse cardiac and cerebrovascular events (MACCE), modifications in the National Institutes of Health Stroke Scale (NIHSS) values for minor stroke patients, and postoperative stroke and death rates. Results Technical and procedural success rates were 100% and 97.4%, respectively; 1 intraoperative minor stroke occurred due to stent thrombosis. At 30 days, 2 patients had recurrent minor stroke; one subsequently died after a hemorrhagic brain infarction. The MACCE rate was 3.8%. There were no cases of myocardial infarction or access-related complications. Of the 20 surviving minor stroke patients, 14 showed improvement in neurological deficit on the NIHSS scale at 30 days, while 5 remained stable and one was neurologically impaired. Conclusion Urgent CAS in selected patients with symptomatic carotid stenosis was satisfactory in preventing the recurrence of TIA and stroke in this study. Urgent CAS with careful patient selection, contemporary tools (medical and technical), and expert technique may represent a possible solution for some patients with recent or recurrent TIA or minor stroke.

Surgical treatment of posterior nutcracker syndrome

Posterior nutcracker syndrome (PNS) is a rare condition due to left renal vein (LRV) hypertension, caused by compression of the LRV between the vertebral column and the abdominal aorta. Diagnosis of PNS is challenging, as symptoms are variable and not specific. Therapeutic options are debated, and either conservative, open, or endovascular approaches have been advocated as both safe and effective. We report our experience with a case of PNS in a 17-year-old woman, who presented with a 2 year history of recurrent hematuria associated to severe left flank and back pain, successfully treated with anterior transposition of the LRV.

Midterm Outcomes of the Nellix Endovascular Aneurysm Sealing System A Dual-Center Experience

Purpose: To report midterm outcomes of the Nellix Endovascular Aneurysm Sealing (EVAS) System in the treatment of abdominal aortic aneurysm (AAA). Methods: Between September 2013 and July 2014, 64 AAA patients (mean age 76.6±6.8 years; 61 men) were treated with the EVAS system at 2 centers (only procedures performed at least 12 months prior to the analysis were included). Most patients were treated for a stable AAA, while 1 patient was treated for a ruptured aneurysm. Mean aneurysm diameter was 57.3±9.3 mm. The proximal neck measured a mean 21.5±3.3 mm in diameter and 27.0±12.1 mm long; the neck angle was 16.9°±19.3°. Eleven (17.2%) patients were treated outside the instructions for use (IFU). Results: Technical success was achieved in 63 (98.4%) of 64 patients; 1 type Ia endoleak was treated intraoperatively. One (1.6%) aneurysm-related death occurred at 4 months due to a secondary aortoenteric fistula. Overall, endoleaks occurred in 3 (4.7%) patients (2 type Ia, 1 type II). The estimated rates for 18-month overall survival, freedom from aneurysm-related death, and freedom from secondary interventions were 92.7%, 98.4%, and 95.0%, respectively. Patients treated outside the IFU had a significantly higher incidence of device-related complications (p=0.03). Conclusion: The use of the Nellix device in everyday clinical practice is safe and offers promising midterm results. The risk of secondary aortoenteric fistula requires further analysis. Longer follow-up is needed to assess the actual efficacy of the device, although the risk of migration with late endoleak seems low.

Bifurcated coronary stents for infrapopliteal angioplasty in critical limb ischemia

OBJECTIVE The goal of this article is to report the preliminary results of infrapopliteal percutaneous transluminal angioplasty stenting with the Nile Croco coronary bifurcated stent (Minvasys, Gennevilliers, France) for selected patients with critical limb ischemia (CLI). METHODS From October 2006 to December 2010, 31 patients with CLI with below-the-knee TransAtlantic Inter-Society Consensus C and D lesions at the popliteal (n = 17, 54.8%) and distal tibioperoneal trunk (n = 14, 45.2%) bifurcations, with suboptimal primary percutaneous transluminal angioplasty results (residual stenosis >30%, elastic recoiling, or dissection), with at least two-vessel runoff to the foot (present or after percutaneous transluminal angioplasty), free of aortoiliac arterial disease, and at high surgical risk (more than three risk factors) were treated with the Nile Croco coronary bifurcated stent. Study end points included technical success, immediate and midterm primary and secondary patency rates, clinical improvement, and limb salvage. RESULTS Technical success was achieved in all patients (100%) without any intraoperative complications. Early complications included an acute stent occlusion and an acute compartment syndrome for a collateral arterial branch perforation. Median follow-up was 12.1 months (range, 1-32). Primary and secondary patency rates were 96.7% and 86.2% (95% confidence interval [CI], 67.2%-94.6%) at 30 days and and 100% and 96.6% (95% CI, 78.0%-99.5%) at 1 year, respectively. Clinical improvement (an upward shift of at least two Rutherford categories) was achieved in 28 patients (90.3%). A major amputation was required in one patient (3.2%). The overall limb salvage rate at 1 year was 96.7% (95% CI, 78.6%-99.5%). CONCLUSIONS Preliminary data suggest that the Nile Croco bifurcated stent for below-the-knee angioplasty in selected patients with CLI is associated with high rates of technical success, early and midterm patency, and clinical improvement. Limb salvage rates are acceptable for this technically highly challenging anatomy, yet further studies with larger patient populations are necessary to validate these results.

Eight-year experience with carotid artery stenting for correction of symptomatic and asymptomatic post-endarterectomy defects

BACKGROUND Carotid endarterectomy (CEA) has been shown to be superior to medical therapy alone in the prevention of stroke only if it can be safely performed (ie, with a complication rate less than 3% in asymptomatic patients and less than 6% in symptomatic patients). Technical defects are the most common cause of neurological complications after CEA, and their correction has traditionally been performed through standard surgical techniques. METHODS From 1999, we started to treat intimal flaps, dissection, or partial thrombosis after CEA with carotid artery stenting (CAS). A retrospective analysis of the operating room registry and of the registry of our Interventional Cardiology laboratory was conducted in order to identify all the patients that underwent stenting of the internal carotid artery after CEA between January 2001 and June 2009. RESULTS During the time period considered, 5012 CEA were performed at our institution and a total of 34 patients (34/5012; 0.6%) were found to have received carotid stenting after CEA, both for symptomatic and asymptomatic defects. Immediate technical success was obtained in all patients. One major cerebrovascular adverse event (1/34; 3%) in the immediate perioperative period was recorded. At a mean follow-up of 18.6 months (range, 3-84 months; median, 12 months), we did not observe any neurological symptoms related to the treated carotid artery, nor hemodynamic in-stent restenosis. Long-term follow-up (ie, equal or greater than 4 years) was available for five patients: all patients remained event-free during the entire period. CONCLUSIONS Our study adds to the assumption that CAS in post-CEA symptomatic and asymptomatic patients is safe and technically feasible, and represents a valid and quick alternative to standard surgical revision. Even if in a small group of patients, long-term results seem promising.