Extracellular vesicles as potential biomarkers of acute graft-vs-host disease.

Acute graft-vs-host disease (GVHD) is a serious complication after allografting. We carried out an exploratory study to investigate a potential correlation of surface antigens on extracellular vesicles (EVs) and acute GVHD. EVs were extracted from serum samples from 41 multiple myeloma patients who underwent allografting. EVs were characterized by flow cytometry using a panel of 13 antibodies against specific membrane proteins that were reported to be predictive of acute GVHD. We observed a correlation between three potential biomarkers expressed on EV surface and acute GVHD onset by both logistic regression analysis and Cox proportional hazard model. In our study, CD146 (MCAM-1) was correlated with an increased risk-by almost 60%-of developing GVHD, whereas CD31 and CD140-α (PECAM-1 and PDGFR-α) with a decreased risk-by almost 40 and 60%, respectively. These biomarkers also showed a significant change in signal level from baseline to the onset of acute GVHD. Our novel study encourages future investigations into the potential correlation between EVs and acute GVHD. Larger prospective multicenter studies are currently in progress.

Relevance of sample preparation for flow cytometry.

INTRODUCTION: Flow cytometry is a useful tool for diagnosis and minimal residual disease (MRD) study of hematological diseases. Standard sample preparation protocols are characterized by stain-lyse-wash (SLW). To prevent nonspecific bindings and achieve high sensitivity in MRD studies, lyse-wash-stain-wash (LWSW) is required. To our knowledge, no comparison between the two methods has been performed. METHODS: We compared mean fluorescence intensity (MFI), stain index, signal-to-noise ratio, and percentage of positive cells of 104 antibodies and of 13 selected antibodies tested in 10 samples simultaneously prepared with the two methods. RESULTS: MFI and percentages of positive cells obtained by the two methods did not show significant differences and showed a very high correlation. Stain index and signal-to-noise ratio presented higher values for kappa and lambda surface chains in LWSW samples and a trend of higher values for the other antibodies in SLW samples. CONCLUSIONS: We suggest to use LWSW method also at diagnosis to obtain more comparable antibody intensity expressions when samples from the same patient are processed for MRD evaluation after bulk lysis. Moreover, LWSW can prevent nonspecific bindings, shows no differences in the identification and quantitation of the populations of interest, and reduces acquisition of cell debris.

Autologous transplant vs oral chemotherapy and lenalidomide in newly diagnosed young myeloma patients: a pooled analysis.

In newly diagnosed myeloma patients, upfront autologous transplant (ASCT) prolongs progression-free survival 1 (PFS1) compared with chemotherapy plus lenalidomide (CC+R). Salvage ASCT at first relapse may still effectively rescue patients who did not receive upfront ASCT. To evaluate the long-term benefit of upfront ASCT vs CC+R and the impact of salvage ASCT in patients who received upfront CC+R, we conducted a pooled analysis of 2 phase III trials (RV-MM-209 and EMN-441). Primary endpoints were PFS1, progression-free survival 2 (PFS2), overall survival (OS). A total of 268 patients were randomized to 2 courses of melphalan 200 mg/m2 and ASCT (MEL200-ASCT) and 261 to CC+R. Median follow-up was 46 months. MEL200-ASCT significantly improved PFS1 (median: 42 vs 24 months, HR 0.53; P<0.001), PFS2 (4 years: 71 vs 54%, HR 0.53, P<0.001) and OS (4 years: 84 vs 70%, HR 0.51, P<0.001) compared with CC+R. The advantage was noticed in good and bad prognosis patients. Only 53% of patients relapsing from CC+R received ASCT at first relapse. Upfront ASCT significantly reduced the risk of death (HR 0.51; P=0.007) in comparison with salvage ASCT. In conclusion, these data confirm the role of upfront ASCT as the standard approach for all young myeloma patients.

A phase 2 study of three low-dose intensity subcutaneous bortezomib regimens in elderly frail patients with untreated multiple myeloma.

This phase 2 trial evaluated three low-dose intensity subcutaneous bortezomib-based treatments in patients ⩾75 years with newly diagnosed multiple myeloma (MM). Patients received subcutaneous bortezomib plus oral prednisone (VP, N=51) or VP plus cyclophosphamide (VCP, N=51) or VP plus melphalan (VMP, N=50), followed by bortezomib maintenance, and half of the patients were frail. Response rate was 64% with VP, 67% with VCP and 86% with VMP, and very good partial response rate or better was 26%, 28.5% and 49%, respectively. Median progression-free survival was 14.0, 15.2 and 17.1 months, and 2-year OS was 60%, 70% and 76% in VP, VCP, VMP, respectively. At least one drug-related grade ⩾3 non-hematologic adverse event (AE) occurred in 22% of VP, 37% of VCP and 33% of VMP patients; the discontinuation rate for AEs was 12%, 14% and 20%, and the 6-month rate of toxicity-related deaths was 4%, 4% and 8%, respectively. The most common grade ⩾3 AEs included infections (8-20%), and constitutional (10-14%) and cardiovascular events (4-12%); peripheral neuropathy was limited (4-6%). Bortezomib maintenance was effective and feasible. VP, VCP and VMP regimens demonstrated no substantial difference. Yet, toxicity was higher with VMP, suggesting that a two-drug combination followed by maintenance should be preferred in frail patients.

Osteolytic lesions, cytogenetic features and bone marrow levels of cytokines and chemokines in multiple myeloma patients: Role of chemokine (C-C motif) ligand 20.

The relationship between bone marrow (BM) cytokine and chemokine levels, cytogenetic profiles and skeletal involvement in multiple myeloma (MM) patients is not yet defined. This study investigated a cohort of 455 patients including monoclonal gammopathy of uncertain significance (MGUS), smoldering MM and symptomatic MM patients. Skeletal surveys, positron emission tomography (PET)/computerized tomography (CT) and magnetic resonance imaging (MRI) were used to identify myeloma bone disease. Significantly higher median BM levels of both C-C motif Ligand (CCL)3 and CCL20 were found in MM patients with radiographic evidence of osteolytic lesions as compared with those without, and in all MM patients with positive PET/CT scans. BM levels of CCL3, CCL20, Activin-A and Dickkopf-1 (DKK-1) were significantly higher in patients with high bone disease as compared with patients with low bone disease. Moreover, CCL20 BM levels were significant predictors of osteolysis on X-rays by multivariate logistic analysis. On the other hand, DKK-1 levels were related to the presence of MRI lesions independently of the osteolysis at the X-rays. Our data define the relationship between bone disease and the BM cytokine and chemokine patterns highlighting the tight relationship between CCL20 BM levels and osteolysis in MM.

Clinical impact of immunophenotypic remission after allogeneic hematopoietic cell transplantation in multiple myeloma.

Immunophenotypic remission (IR) is a strong prognostic factor in myeloma patients. The combination of IR and conventional CR was retrospectively evaluated in 66 patients after allografting. IR was defined as the absence of monoclonal plasma cells in BM aspirates by multiparameter flow cytometry. Conditioning was non-myeloablative in 55 patients; reduced-intensity in 10 and myeloablative in 1 patient. The allograft was given upfront in 35/66 (53%) patients. After a median follow-up of 7.1 years, 24 patients achieved both CR and IR (CR/IR group), 21 achieved IR but not CR with persistence of a urine/serum M-component (no CR/IR group) and 21 did not achieve either CR or IR (no CR/no IR group). Median OS and EFS were 'not reached' and 59 months in the CR/IR group; 64 and 16 months in the no CR/IR; and 36 and 6 months in the no CR/no IR, respectively (P<0.001). Cumulative incidence of extramedullary disease was 4.4% in the CR/IR, 38.1% in the no CR/IR and 14.3% in the no CR/no IR groups, respectively, at 4 years (P<0.001). IR was a valid tool to monitor residual disease after allografting, and allowed definition of a cohort of patients at higher incidence of extramedullary relapse.

Appraising failure of surgical and percutaneous revascularization: long term outcomes from an observational registry.

AIM: Many randomized trials have compared coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) in terms of efficacy, but data comparing outcomes of patients in which these two techniques have failed are lacking. METHODS: We included patients undergoing PCI at our center between July 2002 and December 2004. Subjects were distinguished in 2 groups: those with at least one occluded or stenotic saphenous vein graft (CABG failure), and those with at least one stent with angiographically documented restenosis (PCI failure). The primary endpoint was the long-term rate of major adverse clinical events. RESULTS: Two hundred and thirthy four patients were included, with a medium follow up of 61±13 months; 134 were assigned to the CABG failure group, and 104 to the PCI failure group, sharing high rates of baseline risk factors. At long term rates of death were higher in post CABG group (22.1% vs. 9.9%; P=0.015, RR 2.24 C.I. 95% 1.14-4.40) while death rates in patients with diagnosis of diabetes mellitus (24.0% vs. 23.5%; P=0.969, RR 1.020 C.I. 95% 0.38-2.74) were not different CONCLUSION: PCI can be safely offered to both these kinds of patients: as recently demonstrated post CABG outcomes seem to be more favorable in patients with diabetes mellitus.

Mid-term prognostic value of coronary artery disease in patients undergoing transcatheter aortic valve implantation: a meta-analysis of adjusted observational results.

AIMS: Coronary artery disease (CAD) negatively affects prognosis in patients undergoing surgical aortic valve replacement, being currently evaluated in the most common used risk score. Our meta-analysis aims to clarify the prognostic role of CAD on mid-term survival in patients undergoing TAVI. METHODS AND RESULTS: Studies reporting multivariate predictors of adverse outcomes in patients undergoing TAVI were systematically searched for and pooled, when appropriate, using a random-effect method. 960 citations were first screened and finally 7 studies (2472 patients) were included. Diagnosis of CAD was reported in 52%(42-65) of patients and 1169 Edwards SAPIEN and 1303 CoreValve prostheses were implanted. After a median follow up of 452 days (357-585) 24% of patients (19-33) died, and 23 (14-32) for cardiovascular death. At pooled analysis of multivariate approach, diagnosis of coronary artery disease did not increase risk of death (OR 1.0, 95% CI, confidence interval, 0.67-1.50 I(2) 0%). CONCLUSION: CAD does not affect mid-term TAVI outcome: this finding should be weighted to accurately evaluate risk and strategies for patients with severe aortic stenosis.

Incidence and very long- term outcomes of stent thrombosis after bare-metal or drug-eluting stent implantation: a retrospective analysis.

AIM: Stent thrombosis is a major safety issue after percutaneous coronary intervention (PCI) with stent implantation and it is associated with major early and mid-term complications. However, its long-term impact has been incompletely described. We thus aimed to appraise incidence, predictors and very long-term outlook of stent thrombosis after bare metal stent (BMS) or drug-eluting stent (DES) implantation. METHODS: We identified all patients undergoing PCI with BMS or DES at our center between July 2002 and June 2004. For the purpose of this study, we employed a composite definition of stent thrombosis including any Academic Research Consortium stent thromboses (definite, probable, or possible). We adjudicated the following clinical events: death, myocardial infarction (stent thrombosis related), repeated revascularization, and the composite of these events (i.e., major adverse cardiac events, MACE). RESULTS: A total of 1112 patients were included, 854 (76.8%) treated with BMS and 258 (23.2%) treated with DES. At a median follow-up of 61.2 (11.03) months the incidence of stent thrombosis was 20 (1.8%), with 14 (1.3%) definite, 4 (0.4%) probable, and 2 (0.1%) possible according to the American Research Consortium statement. Patients developing stent thrombosis were more likely to have more complex angiographic features at baseline (including angiographically evident thrombus, 4 [20%] vs. 73 [6.6%], P=0.02) and a saphenous vein graft as target vessel (2 [10%] vs. 28 [2.5%], P=0.04). Conversely, being treated with a BMS or a DES did not confer any significant decrease or increase in the risk of stent thrombosis, as 7 [35%] of those with stent thrombosis had received at least a DES vs. 251 [22.9%] of those without stent thrombosis, P=0.28). Early clinical outcomes (at 30 days) distinguishing those with stent thrombosis versus those without were as follows: death in four (20%) vs. 2 (0.2%, P<0.001), myocardial infarction in 1 (5%) vs. 7 (0.6%, P=0.02), revascularization in 5 (25%) vs. 43 (3.9%, P<0.001), and MACE in 8 (40%) vs. 53 (4.8%, P<0.001). After more than 60 months of clinical follow-up, outcomes were as follows: death in 7 (35%) vs. 147 (13.5%, P=0.057), myocardial infarction in 6 (30%) vs. 40 (3.6%, P<0.001), revascularization in 15 (75%) vs. 317 (29%, P<0.001), and MACE in 19 (95%) vs. 453 (41.5%, P<0.001). CONCLUSION: This long-term registry shows that stent thrombosis remains a major safety issue after PCI with stent implantation, with a significant prognostic impact. However, in the present work the risk of stent thrombosis was similar with either DES or BMS, suggesting thus that DES are not associated with any increase in long-term thrombotic risk in comparison to BMS.

Lenalidomide-prednisone induction followed by lenalidomide-melphalan-prednisone consolidation and lenalidomide-prednisone maintenance in newly diagnosed elderly unfit myeloma patients.

This multicenter phase II trial evaluated the safety and efficacy of lenalidomide-prednisone (RP) induction, followed by lenalidomide-melphalan-prednisone (MPR) consolidation and RP maintenance in elderly unfit newly diagnosed myeloma patients. Patients received four 28-day RP induction courses (lenalidomide 25 mg/day on days 1-21 and prednisone 50 mg three times/week), followed by six 28-day MPR consolidation cycles (melphalan 2 mg, prednisone 50 mg three times/week and lenalidomide 10-15 mg/day on days 1-21), and maintenance with lenalidomide (10 mg/day on days 1-21 every 28 days) plus prednisone (25 mg three times/week). Forty-six patients were enrolled. Median age was 75 years, 59% of patients had at least one comorbidity and 35% at least two. Partial response rate was 80%, including 29% very good partial response. Median time to progression was 19.6 months, median progression-free survival was 18.4 months and 2-year overall survival was 80%. At the tolerated consolidation dose (melphalan 25 mg/month and lenalidomide 10 mg/day), the most frequent grade 3 adverse events were neutropenia (36.4%), anemia (12.1%), cutaneous reactions (18.2%) and infections (12.1%). Grade 4 neutropenia occurred in 12.1% of patients. In conclusion, RP induction followed by MPR consolidation and RP maintenance showed a manageable safety profile, and reduced the risk of severe hematological toxicity in unfit elderly myeloma patients.

Very long-term outcome of peripheral arterial disease in patients undergoing percutaneous coronary revascularization: a retrospective analysis.

AIM: Peripheral arterial disease (PAD) in patients undergoing percutaneous coronary intervention (PCI) with stent implantation is a well known risk factor leading to an increased rates of stroke, cardiovascular death and myocardial infarction. Anyway there are few data on very-long term outcome (more than 1 year follow up) of PAD after stent implantation. We thus aimed to evaluate the influence of PAD on very long-term outcome of our PCI-population. METHODS: We retrospectively identified all patients undergoing PCI with stent implantation at our center between July 2002 and June 2004, and thus eligible for at least 4 years of follow-up. For the purpose of this study, we considered a diagnosis of PAD based on clinical evaluation and/or angiographic documentation. We adjudicated the following clinical events: death, myocardial infarction, repeat revascularization, and their composite (i.e. major adverse cardiac events, MACE). RESULTS; A total of 1008 patients were included, 109 with PAD and 899 Without PAD. Those with had more often diabetes (35% vs. 25%, P=0.002), hypertension (83% vs. 68%, P=0.001) and unfavorable basal clinical condition at the start of this study: past-Percutaneous Coronary Intervention (PCI) (30% vs. 22%, P=0.005), past-Coronary Artery Bypass Graft (CABG) (24% vs. 14%, P=0.001), ejection fraction (EF) <35% (14% vs. 7%, P=0.02) and chronic renal failure (CRF) (15% vs. 6%, P=0.002). In addiction patient with PAD were more likely to have chronic total occlusion (CTO) (36% vs. 25%, p=0.02) and unprotected left main (16% vs. 8%,P=0.01). Clinical outcome at the time of follow-up (4,42 ± 1,66 years) was as follow: Revascularization (53% vs. 37%, P=0.002), Cardiac death (21% vs. 13%, P=0.04), MACE (69% vs. 49%, p<.001). Independent predictors of MACE according to our survival analysis were: PAD (HR 1.31; 95% CI 1.01-1.69), Age >75 (HR 1.23; 95% CI 1-1.51), Chronic heart failure (HR1.72; 95% CI 1.19-2.5), Unprotected left main (HR 1.48; 95% CI 1.12-1.96). CONCLUSION: This long-term registry shows that PAD remains an important clinical condition that negatively influences the outcome of patients undergoing PCI with stent implantation in a very long-term follow-up period.

Short and long term outcome of percutaneous coronary intervention with drug eluting stent and bare metal stent in patients with chronic kidney disease.

AIM: Coronary artery disease represents the most important cause of mortality and morbidity in chronic kidney disease (CKD). Despite continuous improvements in percutaneous coronary intervention (PCI), CKD is still associated with more adverse events after PCI. We performed a retrospective study to compare bare metal stents (BMS) versus drug eluting stents (DES) in CKD. METHODS: We included consecutively all patients undergoing PCI at our Centre from July 2002 to December 2005 with CKD, defined as creatinine clearance <60 mL/min. Patients who received only DES were compared to those who received only BMS. The primary end-point was the long-term rate of major adverse cardiac events (MACE, i.e. the composite of death, myocardial infarction and repeat revascularization). RESULTS: We included a total of 219 patients with CKD out of a total of 2354 patients, with 164 receiving BMS and 55 DES. After a mean follow up of 48 months, the MACE rate was significantly higher in BMS group (71% versus 38%, P<0.001). A similarly increased risk with BMS was found for death (45% versus 17%, P<0.001), whereas the rates for repeat coronary revascularization, myocardial infarction and stent thrombosis were not significantly different. Multivariable analysis showed that BMS vs.. DES implantation was not statistically significant associated with MACE, death, myocardial infarction, rePTCA or stent thrombosis. CONCLUSION: Compared with BMS, use of DES in patients with CKD is safe and effective in reducing adverse outcomes. However, differences found between groups in clinical end-point could be ascribed to selection bias and confounding factors.

Syndecan-1 promotes the angiogenic phenotype of multiple myeloma endothelial cells.

Angiogenesis is considered a hallmark of multiple myeloma (MM) progression. In the present study, we evaluated the morphological and functional features of endothelial cells (ECs) derived from bone marrow (BM) of patients affected by MM (MMECs). We found that MMECs compared with normal BM ECs (BMECs) showed increased expression of syndecan-1. Silencing of syndecan-1 expression by RNA interference technique decreased in vitro EC survival, proliferation and organization in capillary-like structures. In vivo, in severe combined immunodeficient mice, syndecan-1 silencing inhibited MMEC organization into patent vessels. When overexpressed in human umbilical vein ECs and BMECs, syndecan-1 induced in vitro and in vivo angiogenic effects. Flow-cytometric analysis of MMECs silenced for syndecan-1 expression indicated a decreased membrane expression of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2). Immunoprecipitation and confocal analysis showed colocalization of VEGFR-2 with syndecan-1. Absence of nuclear translocation of VEGFR-2 in syndecan-1-knockdown cells together with the shift from perinuclear localization to recycling compartments suggest a role of syndecan-1 in modulation of VEGFR-2 localization. This correlated with an in vitro decreased VEGF-induced invasion and motility. These results suggest that syndecan-1 may contribute to the highly angiogenic phenotype of MMECs by promoting EC proliferation, survival and modulating VEGF-VEGFR-2 signalling.

Stem cell mobilization in patients with newly diagnosed multiple myeloma after lenalidomide induction therapy.

Lenalidomide has raised concerns regarding its potential impact on the ability to collect stem cells for autologous stem cell transplantation, especially after prolonged exposure. The use of cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) to mobilize peripheral blood stem cells may overcome this concern. In newly diagnosed multiple myeloma (MM) patients, we investigated the influence of lenalidomide on stem cell collection. In a prospective study, 346 patients received four cycles of lenalidomide-dexamethasone (Rd). Stem cells were mobilized with cyclophosphamide and G-CSF. Patients failing to collect a minimum of 4 × 10(6) CD34(+)/kg cells received a second mobilization course. After mobilization, a median yield of 8.7 × 10(6) CD34(+)/kg was obtained from patients receiving Rd induction. After first mobilization, inadequate yield was observed in 21% of patients, whereas only 9% of patients failed to collect the target yield after the second mobilization attempt. In conclusion, we confirm that a short induction with lenalidomide allowed sufficient stem cells collection to perform autologous transplantation in 91% of newly diagnosed patients.

Percutaneous drug-eluting stent implantation in diabetic patients: short and long term outcomes from an observational study.

AIM: The introduction of drug-eluting stents (DES) has markedly improved mid-term results of percutaneous coronary intervention (PCI) in diabetics. However, it is unclear whether the risk-benefit balance of DES in diabetics is maintained also at long-term and in insulin-requiring patients. We thus aimed to appraise long-term outcomes of diabetic patients treated with PCI with DES, stratifying according to insulin therapy. METHODS: We retrospectively collected baseline, procedural and outcome data from all patients undergoing PCI with DES from July 2002 to June 2004 at our center. We distinguished three groups: insulin-requiring diabetics, non-insulin-requiring diabetics and patients without diabetes. The primary end-point was the long-term rate of major adverse cardiac events (MACE, i.e. the composite of death, myocardial infarction, or target vessel revascularization). We also considered stent thrombosis according to the Academic Research Consortium Definition. RESULTS: We included a total of 1266 patients, with 3% of insulin-requiring diabetes, 22% with non-insulin-requiring diabetes, and 75% without diabetes. There were significant differences across groups in prevalence of male gender (respectively, 32.4%, 74.6% and 81%, P<0.001), and DES usage (54.1%, 34%, and 30.4%, P=0.007). Thirty-day MACE occurred with similar frequency in the three groups (8.1%, 7.3% and 6.3%, P=0.78), with death in 3%, 2%, and 1.4% (P=0.71) and myocardial infarction in 5.4%, 1.8% and 0.8% (P=0.02). After a median follow-up period of 58 months, MACE occurred in 59.5% of patients with insulin-requiring diabetes, in 50.6% of non-insulin-requiring diabetics and in 38.9% of non-diabetics (P<0.001). Death occurred in 24.3%, 17.5% and 8.5%, (P<0.001), myocardial infarction in 10.8%, 6.6%, and 5.1% (P=0.25), repeat revascularization in 46%, 31.6%, and 30% (P=0.11), and definite stent thrombosis in 0%, 1.1%, and 1.3% (P=0.78). CONCLUSION: Our study confirms the high risk profile of diabetic patients, especially when ischemic disease it is known. In this setting, diabetic and comorbidities fix the price not only in term of need of further revascularization, but mainly in survival decrease. It can be concluded that not only revascularization but also ­ and especially ­ comorbidities treatment plays a determinant role reducing follow-up events. Further research on additional pharmacologic treatments or hybrid revascularization strategies may mitigate the burden of morbidity and mortality.

Short and long-term outcomes of percutaneous revascularization in patients with prior coronary artery bypass graft.

AIM: Patients with prior coronary artery bypass grafting (CABG) represent a sizable portion of those undergoing percutaneous coronary intervention (PCI): in many instances, it is unclear whether performing PCI on the bypass graft or in the native coronary vessels can offer the best risk-benefit balance. METHODS: We included patients with prior CABG undergoing PCI at our center between July 2002 and June 2004 and we distinguished them in three groups. Those in whom PCI was performed on stenotic saphenous vein graft (SVG group), those in whom PCI was performed on native vessels despite the presence of potentially treatable SVG disease (optional native group), and those in whom PCI had to be performed mandatorily in the native vessels because of chronic SVG occlusions or disease in non-bypassed segments (mandatory native group). The primary end-point was long-term rate of major adverse clinical events (MACE, i.e. death, myocardial infarction, or target vessel revascularization). RESULTS: We identified 109 patients: 28 were in the SVG group, 25 in the optional native group, and 56 in the mandatory native group. Early major adverse cardiac events (MACE) occurred with similar frequency in the three groups (respectively, 9.1%, 0% and 5.7%, P=0.35). After more than three years of follow-up, MACE occurred in 39.3% vs. 28 and 39.4% (P=0.59), death occurred in 27.2 vs. 24.0% vs. 13.5% (P=0.30), and TVR in 27.3% vs. 8.0% vs. 28.8% (P=0.14). CONCLUSION: In selected patients, PCI of native coronary vessels despite the presence of apparently treatable SVG lesions can be envisioned.

Impact of multivessel coronary disease on long-term outcome after percutaneous recanalization of coronary chronic total occlusions.

AIM: Percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) is common even with concomitant multivessel disease. We aimed to investigate the impact of multivessel disease on long-term outcome after PCI for CTO. METHODS: We collected baseline, procedural and follow-up data on patients undergoing successful PCI with stenting for CTO. We divided our population into three groups: patients with 1 vessel disease (1VD), those with 2-vessel disease (2VD) and subjects with 3-vessel disease (3VD). The primary end-point was the occurrence of major adverse cardiac events (MACE), i.e. death, myocardial infarction or target vessel revascularization. RESULTS: A total of 111 patients were included: 24 (21%) in group 1VD, 28 (25%) in group 2VD, and 59 (53%) in group 3VD. Clinical follow-up was available in 109 (98%) of them after a median of 27 months (range 6-68), yielding MACE rates of 1 (4%) in group 1VD, 5 (18%) in group 2VD, and 17 (29%) in group 3VD, respectively (P=0.03). No statistically significant difference was found comparing the 3 groups for the individual rates of death, myocardial infarction or target vessel revascularization (all P>0.05). No case of definite or probable stent thrombosis was adjudicated, despite use of DES in 99 (89%) patients. CONCLUSION: Patients with diffuse coronary disease undergoing PCI for a CTO fare a significantly worse prognosis. Nonetheless, despite liberal use of DES, stent thrombosis is rare in this setting, without differences according to the initial severity of disease, thus supporting the long-term safety of DES, even if used in this "off-label" context.