Micaela Conte

CagA antigen of Helicobacter pylori and coronary instability: insight from a clinico-pathological study and a meta-analysis of 4241 cases.

BACKGROUND Cytotoxin-associated gene-A (CagA) antigen is expressed by some virulent strains of Helicobacter pylori (H. pylori). The role of CagA antigen in coronary instability is unknown. We performed a clinico-pathological study and a meta-analysis in the attempt to shed new light on this complex issue. METHODS In the clinico-pathological study, 38 patients with unstable angina (UA), 25 patients with stable angina (SA), 21 patients with normal coronary arteries (NCA) and 50 age and sex matched healthy volunteers were enrolled. Serology for CagA was assessed in all patients. Specimens of atherosclerotic plaques were obtained from all patients by directional coronary atherectomy, and prepared for immunohistochemistry using anti-CagA monoclonal antibodies. The meta-analysis includes 9 studies assessing the association between seropositivity to CagA strains and acute coronary events. RESULTS The titre of anti-CagA antibodies was significantly higher in patients with unstable angina (161+/-90 RU/ml) compared to those with stable angina (83+/-59 RU/ml p<0.02), NCA (47.3+/-29 RU/ml p<0.01) and healthy controls (73+/-69 p<0.02). Anti-CagA antibodies recognized antigens localized inside coronary atherosclerotic plaques in all specimens from both stable and unstable patients. In the meta-analysis, seropositivity to CagA was significantly associated with the occurrence of acute coronary events with an odds ratio (OR) of 1.34 (95% CI, 1.15-1.58, p=0.0003). CONCLUSIONS Taken together these findings suggest that in a subset of patients with unstable angina, an intense immune response against CagA-positive H. pylori strains might be critical to precipitate coronary instability mediated by antigen mimicry between CagA antigen and a protein contained in coronary atherosclerotic plaques.

Long-Term Clinical Outcome After Fractional Flow Reserve–Guided Percutaneous Coronary Revascularization in Patients With Small-Vessel Disease

Background— Small coronary vessels supply small myocardial territories. The clinical significance of small-vessel stenoses is therefore questionable. Moreover, percutaneous coronary intervention (PCI) of nonfunctionally significant lesions does not improve clinical outcome and might be associated with potential procedural or stent related risks. The aim of this study was to assess the clinical outcome of fractional flow reserve (FFR)-guided PCI in the treatment of small coronary vessel lesions as compared with an angio-guided PCI. Methods and Results— From January 2004 to December 2008, all patients treated with PCI for stable or unstable angina in small native coronary vessels (reference vessel diameter and stent size <3 mm) were retrospectively analyzed. Patients were divided into angio-guided and an FFR-guided PCI groups. A total of 717 patients were enrolled (495 angio-guided, 222 FFR-guided). End points were death, nonfatal myocardial infarction (MI), combined death or nonfatal MI, target vessel revascularization (TVR), and procedure costs. Major adverse cardiac events (MACE) were defined as death, nonfatal MI, and TVR. Clinical follow-up was obtained in 97.5% (median follow-up: 3.3 [from 0.01–5] years) of the patients. Seventy-eight patients (35%) had a significant FFR (<0.80) and underwent PCI. Using a propensity score adjusted Cox analysis, patients treated with FFR-guided PCI had significantly lower combined death or nonfatal MI (hazard ratio [HR], 0.413; 95% confidence interval [CI], 0.227–0.750; P=0.004), nonfatal MI (HR, 0.063; 95% CI, 0.009–0.462; P=0.007), TVR (HR, 0.517; 95% CI, 0.323–0.826; P=0.006), and MACE (HR, 0.458; 95% CI, 0.310–0.679; P<0.001). No difference was observed in mortality alone (HR, 0.684; 95% CI, 0.355–1.316; P=0.255). Procedure costs were also reduced in the FFR guided strategy (3253±102 Euros versus 4714±37 Euros, P<0.0001). Conclusions— FFR-guided PCI of small coronary arteries is safe and results in better clinical outcomes when compared with an angio-guided PCI.

Coronary atherosclerotic burden in patients with infection by CagA-positive strains of Helicobacter pylori

ObjectivesCytotoxic associated gene-A (CagA)-positive strains of Helicobacter pylori emerged as a possible atherosclerotic stimulus. Nevertheless, whether CagA-positivity is associated with more extensive or severe atherosclerotic coronary burden has never been studied. MethodsForty consecutive patients with coronary artery disease (CAD) and twenty consecutive patients with normal coronary arteries undergoing coronary angiography were enrolled. All patients underwent evaluation of classical atherogenic risk factors and assessment of anti-urease B and anti-CagA antibodies titer. Either the severity of coronary stenosis (stenosis score) or the extent of coronary atherosclerosis (extent score) was evaluated in CAD patients. ResultsThe anti-CagA antibody titer was significantly higher in patients with CAD as compared with normal coronary arteries patients [85 (10–108.75) vs. 47.3 (17–64) RU/ml, P=0.02], whereas there were no differences in anti-urease B titer between the two groups. A significant correlation was found between anti-CagA antibody titer and extent score (R=0.35, P=0.03), whereas stenosis score was similar (R=0.25, P=0.11). On the contrary, no significant correlation was found between anti-urease B antibody titer and either extent or stenosis score. Moreover, CagA-positive patients had a more extensive CAD (P=0.029) when compared with CagA-negative patients. Interestingly, whereas serum glucose, LDL levels, anti-urease B, and anti-CagA antibodies were predictors of extent score at univariate analysis, at multivariate analysis anti-CagA antibody titer only was an independent predictor of the extent of coronary atherosclerosis (B=0.051, standard error of B=0.042, P=0.04). ConclusionThese results support the association between CagA-positive H. pylori infection and coronary atherosclerotic burden. Further studies are needed to better elucidate the mechanism by which CagA-positive strains may promote atherosclerosis.

Pre-intervention eosinophil cationic protein serum levels predict clinical outcomes following implantation of drug-eluting stents

AIMS Eosinophils have been identified in post-mortem studies as important players of both restenosis and thrombosis after drug-eluting stent (DES) implantation. We aimed at assessing the association between baseline levels of eosinophil cationic protein (ECP), a marker of eosinophil activation, and recurrence of clinical events in a consecutive series of patients who underwent DES implantation. METHODS AND RESULTS Two hundred patients (age 63 +/- 10.4, males 75%) undergoing implantation of first-generation DES (Taxus or Cypher stents) were enrolled. We measured serum levels of ECP and total IgE by enzyme-linked immunosorbent assay and of C-reactive protein by high-sensitivity nephelometry prior to percutaneous coronary intervention. A clinical follow-up was planned 18 months after discharge. Major adverse cardiac events (MACEs), such as cardiac death, recurrent myocardial infarction, or clinically driven target lesion revascularization, were the endpoint of the study. Twenty-two patients (11%) had MACEs and showed higher serum levels of ECP compared with those without MACEs [30.5 (14.4-50) vs. 12.2 (4.4-31) microg/L, P = 0.004]. At simple Cox regression analysis, serum levels of ECP were a significant predictor of MACEs (hazard ratio 1.016, 95% confidence interval 1.003-1.03, P = 0.018). CONCLUSION This study shows for the first time an association between baseline ECP levels and the occurrence of MACEs in patients undergoing implantation of DES. Further studies are warranted to establish whether in this setting ECP is a risk marker or plays a contributory pathogenetic role.

Eosinophil cationic protein: A new biomarker of coronary atherosclerosis

AIMS Coronary atherosclerosis is a chronic inflammatory disease, but different inflammatory biomarkers may reflect different phases of atherosclerotic plaque evolution. We aimed at assessing the role of eosinophil cationic protein (ECP), a sensitive marker of eosinophil activation, and C-reactive protein (CRP) in coronary artery disease (CAD). METHODS AND RESULTS Consecutive anginal patients with angiographic evidence of CAD [stable angina (SA) or non-ST-elevation acute coronary syndrome (NSTE-ACS)], or with angiographically normal coronary arteries (NCA) were enrolled. The severity of CAD was graded according to Bogatys score and coronary lesion morphology was defined as smooth or complex. Baseline ECP and high sensitivity CRP were measured in all patients. Of 198 patients (64 + or - 10 years, male 74%), 91 had SA, 57 had NSTE-ACS and 50 had NCA. ECP levels were significantly higher in SA [30 microg/L (13.8-46.9), p<0.001] and NSTE-ACS [21.8 microg/L (5.5-46.3), p=0.016] compared to NCA [9.7 microg/L (6.1-13.6)], without significant difference between SA and NSTE-ACS (p=0.45). CRP levels were significantly higher in NSTE-ACS [2.38 mg/L (1.11-11.94)] compared to SA [1.48 mg/L (0.82-2.83), p=0.03], and NCA [1.09 mg/L (0.8-2.1), p<0.001], without significant difference between SA and NCA (p=0.20). The addition of ECP to main cardiovascular risk factors improved the area under the curve from 0.88 to 0.92, p=0.007 for the angiographic diagnosis of CAD; further addition of CRP increased the area to 0.94, p=0.014. At multiple linear regression analysis ECP levels independently predicted CAD severity (p=0.001), whereas CRP levels independently predicted lesion complexity (p=0.01). CONCLUSIONS Our study shows that ECP is a marker of CAD and that different inflammatory biomarkers reflect different phases of atherosclerotic plaque evolution.

Kissing inflation is feasible with all second-generation drug-eluting balloons.

OBJECTIVE To assess the feasibility of kissing second-generation drug-eluting balloons (DEB), which have better mechanical properties than the first-generation DEB, in order to optimize provisional bare-metal stenting (BMS) when treating coronary bifurcation lesions in patients with contraindication to drug-eluting stents. METHODS Consecutive patients with anticipated low compliance to dual antiplatelet therapy who are undergoing provisional stenting with an open-cell design BMS and final kissing balloon with second-generation DEB were enrolled in this feasibility study. Angiographic success and procedural success (i.e., angiographic success in absence of in hospital major cardiovascular events) were registered. Clinical follow-up was also attempted in all patients. RESULTS A total of 14 patients (mean age 66±9 years, nine men) participated on the study. The DEB used were SeQuent Please (B. Braun Melsungen, Berlin, Germany) in six patients, In.Pact Falcon (Medtronic Invatec, Roncadelle, Italy) in four patients, New Dior (Eurocor, Bonn, Germany) in two patients and Pantera Lux (Biotronik, Berlin, Germany) in another two patients. All procedures, but one, were performed by transradial access through a 6-French high-flow guiding catheter. True bifurcation was present in 50% of the patients. Angiographic and procedural success was obtained in all patients. At a mean follow-up of 234±81 days, all contacted patients were asymptomatic and free from major adverse cardiac events (including cardiac death, nonfatal myocardial infarction and target bifurcation revascularization). CONCLUSION At the advent of dedicated bifurcation stents, kissing DEB appears safe and effective and can be used to implement innovative, simpler, safer and possibly more effective bifurcation techniques. These remarkable results have laid the ground for an ongoing prospective registry of the kissing DEB technique (KISSING DEBBIE study, ClinicalTrials.gov NCT01009996).

Eosinophil cationic protein and clinical outcome after bare metal stent implantation.

OBJECTIVE we assessed the association between baseline eosinophil cationic protein (ECP) levels, a sensitive marker of eosinophil activation, and clinical outcome in patients undergoing bare metal stent (BMS) implantation. METHODS basal ECP levels were measured in 110 patients (69±11 years, 88 men) undergoing BMS implantation. Major adverse cardiac events (MACEs), defined as cardiac death, non-fatal myocardial infarction, or clinically-driven target lesion revascularization, were registered at 24-month follow-up. RESULTS eighteen (16.4%) patients had MACEs and showed higher ECP levels compared with those without MACEs [20.1 (9.8-47.3) vs. 9.5 (5.0-27.2) g/L, p=0.02]. At follow-up, ECP level>11 g/L was the only significant predictor of MACEs (HR 3.5, 95% CI 1.1-10.4, p=0.03). CONCLUSION basal ECP levels are associated with MACEs after BMS implantation, suggesting that an allergic-mediated inflammation against the metal could explain some adverse reactions occurring after coronary stenting.

Long-term clinical outcome in patients with small vessel disease treated with drug-eluting versus bare-metal stenting

BACKGROUND DES is superior to BMS in reducing restenosis and repeat revascularization. Available data are less convincing in small vessel disease. Aim of our study is to assess long-term clinical outcome of drug-eluting stents (DES) vs. bare-metal stents (BMS) in small coronary vessel disease. METHODS Procedural and long-term clinical outcomes were assessed in consecutive patients (pts) treated with stenting of native small coronary arteries (reference vessel diameter and implanted stent < 3mm). RESULTS Pts enrolled were 645: DES group (n = 277) presented more frequently diabetes (173 [62%] vs. 32 [9%], P < .0001), higher body mass index (27 ± 5 vs. 26 ± 4, P = .01) and with previous PCI (115 [42%] vs. 118 [32%], P = .01) as compared to BMS group (n=368). DES group presented more frequently with unstable angina (46 [17%] vs. 38 [10%], P = .02); BMS group presented more frequently with myocardial infarction (103 [28] vs. 43 [15], P = .0002). Reference vessel (2.27 ± 0.36 vs. 2.24 ± 0.36, P = .29), minimal lumen (0.81 ± 0.32 vs. 0.80 ± 0.31, P = .84) and stent diameter (2.59 ± 0.17 vs. 2.60 ± 0.15, P = .69) did not differ between the 2 groups. Lesion length was significantly higher in DES group (15.85 ± 6.81 vs. 13.66 ± 7.18, P = .01). At a median clinical follow-up of 3.0 years (IQR range 2.2-4.6), pts with DES showed significantly lower major adverse cardiac events (MACE, HR 0.51, 95%CI 0.33-0.78) and target vessel revascularization (TVR, HR 0.44, 95%CI 0.25-0.78). No differences were observed between the two groups as to death, myocardial infarction and stent thrombosis. CONCLUSIONS In small vessel disease, DES was more frequently implanted in pts at higher risk of restenosis, though it demonstrated to be more effective than BMS in reducing MACE and TVR at long-term follow-up.

Safety and effectiveness of drug-eluting stents versus bare-metal stents in elderly patients with small coronary vessel disease

BACKGROUND Drug-eluting stents (DES) are more effective than bare-metal stents (BMS) in small coronary vessel disease. Whether this is true in elderly patients, it is unclear, as frailty and a high rate of comorbidities could increase the rate of DES-related complications. AIMS To assess procedural and long-term clinical outcomes of elderly patients with small vessel disease treated with DES or BMS. METHODS Consecutive elderly patients (≥ 75 years old) treated with stenting of native small coronary arteries (reference vessel diameter and implanted stent<3mm) were recruited during 2004-2008. Procedural and long-term clinical outcomes were compared between patients treated with BMS and DES. Propensity score-adjusted logistic regression analysis was performed to account for potential selection bias. RESULTS Among 293 patients (175 BMS, 118 DES), peri-procedural myocardial infarction (12 [7%] vs. 5 [4%]; P=0.35) and blood transfusions (3 [2%] vs. 0; P=0.08) were not significantly different between the BMS and DES groups. Clinical follow-up (96% of patients, median [interquartile range] follow-up 3.5 [2.4] years) showed significantly lower adjusted major adverse cardiac events (hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.24-0.72; P=0.002) and target vessel revascularization (TVR) (HR 0.33, 95% CI 0.14-0.76; P=0.009) in the DES group. No significant differences were observed between the groups in terms of death, myocardial infarction, stent thrombosis or bleeding. CONCLUSIONS In this retrospective, non-randomized analysis of the treatment of small vessel disease in elderly patients, DES were as safe and more effective than BMS with a significant reduction in TVR.

Laser for complex coronary lesions: impact of excimer lasers and technical advancements.

actual renal outcome after CAG or PCI in a real-world clinical practice setting. The incidence of CIN in this study was comparable to that in the previous studies about CIN and the study population was considered to be valid [3]. Recent reports have suggested that the development of CIN is associated with increased mortality [6], but whether CIN has a causal Fig. 1. Incidence of acute CIN and persistent CIN. effect on mortality or not is yet to be elucidated. Until the causal relationship between CIN and increased mortality is proven, we can regard CIN as a marker indicating vulnerability of the renal and systemic vasculature or instability of the systemic circulation; [7] those patients who develop CIN should be carefully monitored and appropriately treated to prevent late cardiovascular events [8]. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [9].