Giulio Speciale

Role of endothelial progenitor cells in restenosis and progression of coronary atherosclerosis after percutaneous coronary intervention: a prospective study.

OBJECTIVES We prospectively investigated the relationship of circulating endothelial progenitor cells at time of percutaneous coronary intervention to the subsequent development of in-stent restenosis or progression of coronary atherosclerosis. BACKGROUND Endothelial progenitor cells provide an endogenous repair mechanism of the dysfunctional endothelium and therefore can play a pathogenic role in coronary atherosclerosis. METHODS We studied 155 consecutive stable angina patients (92 men, age 60 +/- 11 years). All patients had flow cytometry the day before elective percutaneous coronary intervention in order to derive subpopulations of endothelial progenitor cells. A control group of 20 normal subjects was considered for comparison. RESULTS At 8-month control angiography, 30 patients showed in-stent restenosis (restenosis group), 22 patients showed progression of coronary atherosclerosis (progression group), whereas the remaining 103 patients had neither in-stent restenosis nor progression of coronary atherosclerosis (stable group). Comparison of the 3 groups did not show any difference in risk factors, cardiac morphology and function, extension of coronary artery disease, and treatment. Absolute numbers of CD34+/KDR+/CD45- cells (i.e., progenitors of endothelial lineage) measured in the restenosis group (1.41 +/- 0.64 cells/microl) were significantly higher than in the progression, stable, and control groups (1.03 +/- 0.53 cells/microl, 1.07 +/- 0.46 cells/microl, and 0.95 +/- 0.44 cells/microl, respectively, p < 0.05). Similarly, CD133+/KDR+/CD45- cells (i.e., progenitors of endothelial cells at an earlier stage) were significantly higher in the restenosis (0.63 +/- 0.23 cells/microl) compared with progression, stable, and control groups (0.33 +/- 0.19 cells/microl, 0.41 +/- 0.32 cells/microl, and 0.36 +/- 0.15 cells/microl, respectively, p < 0.001). Also, numbers of CD14+/CD45+ cells (i.e., which have a role in angiogenesis via a paracrine effect) were significantly different among the restenosis, progression, stable, and control groups (0.72 +/- 0.56 cells/microl vs. 0.51 +/- 0.52 cells/microl vs. 0.28 +/- 0.54 cells/microl vs. 0.62 +/- 0.67 cells/microl, respectively, p < 0.05), whereas CD105+/CD45-/CD34- cells (i.e., which have a receptor for transforming growth factor-beta) were similar among groups. CONCLUSIONS Patients with restenosis have higher numbers of subpopulations of endothelial progenitor cells that incorporate into endothelial cells or play a role in arteriogenesis compared with controls and patients with either progression of coronary atherosclerosis or stable disease.

Angiotensin II receptor antagonism with telmisartan increases number of endothelial progenitor cells in normotensive patients with coronary artery disease: A randomized, double-blind, placebo-controlled study

INTRODUCTION Circulating endothelial progenitor cells (EPCs) provide an endogenous repair mechanism of the dysfunctional endothelium and therefore can play a crucial role in the pathophysiology of coronary artery disease (CAD). Angiotensin II receptor antagonism has been shown to be able to increase EPCs in hypertension but its effect in patients with CAD is unknown. Aim of this study was to evaluate whether telmisartan, an angiotensin II receptor antagonist, can modify the number of subpopulations of EPCs and may in turn affect the endothelial function of normotensive patients with CAD. METHODS In a prospective double-blind parallel group study, 40 normotensive patients with CAD were randomly treated with telmisartan (80 mg) or placebo for 4 weeks at time of coronary angiography. Measurements of EPCs and assessment of flow-mediated dilatation (FMD) of the brachial artery was performed before and after therapy. RESULTS Absolute number of EPCs was similar at baseline in the telmisartan and placebo groups. After 4 weeks treatment, CD34+/KDR+/CD45- cells increased significantly in the telmisartan group (from 0.010+/-0.003 to 0.014+/-0.004%, P=0.0001) but not in the placebo group (from 0.009+/-0.004 to 0.009+/-0.005%, NS). Similarly, CD133+/KDR+/CD45- cells raised significantly with telmisartan (from 0.003+/-0.002 to 0.006+/-0.002%, P=0.0001) but not with placebo (from 0.004+/-0.003 to 0.003+/-0.002%, NS). Also, CD14+/CD45+ cells increased significantly with telmisartan (from 0.005+/-0.002 to 0.008+/-0.002%, P=0.0001) and were unchanged with placebo (0.006+/-0.002 vs. 0.005+/-0.003%, NS). FMD improved significantly in patients who received telmisartan (10.4+/-3.9%, P=0.0015 vs. baseline) but did not change in the placebo group (5.9+/-2.8%; P=0.32 vs. baseline; telmisartan vs. placebo, P=0.002). A significant positive correlation was found in the telmisartan group between the improvement in FMD and the increase in CD34+/KDR+/CD45- cells and CD133+/KDR+/CD45- cells (r=0.55, P<0.01, and r=0.49, P<0.05, respectively). CONCLUSION Angiotensin II receptor antagonism with telmisartan increases the number of regenerative EPCs and improves endothelial function in normotensive patients with CAD. These novel effects are interrelated and can explain, at least in part, why telmisartan has beneficial cardiovascular effects independent of its blood pressure lowering action.

Comparison of the feasibility and effectiveness of transradial coronary angiography via right versus left radial artery approaches (from the PREVAIL Study)

It remains undefined if transradial coronary angiography from a right or left radial arterial approach differs in real-world practice. To address this issue, we performed a subanalysis of the PREVAIL study. The PREVAIL study was a prospective, multicenter, observational survey of unselected consecutive patients undergoing invasive cardiovascular procedures over a 1-month observation period, specifically aimed at assessing the outcomes of radial approach in the contemporary real world. The choice of arterial approach was left to the discretion of the operator. Prespecified end points of this subanalysis were procedural characteristics. Of 1,052 patients consecutively enrolled, 509 patients underwent transradial catheterization, 304 with a right radial and 205 with a left radial approach. Procedural success rates were similar between the 2 groups. Compared to the left radial group, the right radial group had longer procedure duration (46 ± 29 vs 33 ± 24 minutes, p <0.0001) and fluoroscopy time (765 ± 787 vs 533 ± 502, p <0.0001). At multivariate analysis, including a parsimonious propensity score for the choice of left radial approach, duration of procedure (beta coefficient 11.38, p <0.001) and total dose-area product (beta coefficient 11.38, p <0.001) were independently associated with the choice of the left radial artery approach. The operators proficiency in right/left radial approach did not influence study results. In conclusion, right and left radial approaches are feasible and effective to perform percutaneous procedures. In the contemporary real world, however, the left radial route is associated with shorter procedures and lower radiologic exposure than the right radial approach, independently of an operators proficiency.

One-year results of the randomized, controlled, short-term psychotherapy in acute myocardial infarction (STEP-IN-AMI) trial

BACKGROUND Previous studies on cognitive and interpersonal interventions have yielded inconsistent results in ischemic heart disease patients. METHODS 101 patients aged ≤ 70 years, and enrolled one week after complete revascularization with urgent/emergent angioplasty for an AMI, were randomized to standard cardiological therapy plus short-term humanistic-existential psychotherapy (STP) versus standard cardiological therapy only. Primary composite end point was: one-year incidence of new cardiological events (re-infarction, death, stroke, revascularization, life-threatening ventricular arrhythmias, and the recurrence of typical and clinically significant angina) and of clinically significant new comorbidities. Secondary end points were: rates for individual components of the primary outcome, incidence of re-hospitalizations for cardiological problems, New York Heart Association class, and psychometric test scores at follow-up. RESULTS 94 patients were analyzed at one year. The two treatment groups were similar across all baseline characteristics. At follow-up, STP patients had had a lower incidence of the primary endpoint, relative to controls (21/49 vs. 35/45 patients; p=0.0006, respectively; NNT=3); this benefit was attributable to the lower incidence of recurrent angina and of new comorbidities in the STP group (14/49 vs. 22/45 patients, p=0.04, NNT=5; and 5/49 vs. 25/45, p<0.0001, NNT=3, respectively). Patients undergoing STP also had statistically fewer re-hospitalizations, a better NYHA class, higher quality of life, and lower depression scores. CONCLUSION Adding STP to cardiological therapy improves cardiological symptoms, quality of life, and psychological and medical outcomes one year post AMI, while reducing the need for re-hospitalizations. Larger studies remain necessary to confirm the generalizability of these results. CLINICAL TRIAL REGISTRATION ClinicalTrial.gov: NCT00769366.

Rationale and trial design of a randomized, controlled study on short-term psychotherapy after acute myocardial infarction: the STEP-IN-AMI trial (Short Term Psychotherapy in Acute Myocardial Infarction).

Objective A number of previous studies addressed the effect of psychological interventions in patients after acute myocardial infarction (AMI), but it is not known whether psychotherapy might be beneficial after medical and interventional therapy of AMI. We designed a randomized, controlled study to assess the effects of a short-term psychotherapy (STP) on the clinical outcomes of patients who underwent an emergency percutaneous coronary intervention after AMI. Methods One hundred consecutive patients undergoing an emergency percutaneous coronary intervention will be randomized 1 week after AMI to medical therapy (control group, C group) or to medical therapy and STP (STP group). Clinical follow-up visits are scheduled at 6 months, 1 and 5 years, whereas psychometric tests (Self-Evaluation test, Modified Maastricht Questionnaire, Social Support Questionnaire, Recent Life Change Questionnaire, Beck Depression Inventory, the MacNew Heart Disease Health-Related Quality of Life Questionnaire, Type D Personality test) are scheduled 1 week after AMI and at 1 year. The primary outcome measures of the study are the cumulative incidence of new cardiological events (myocardial reinfarction, death, stroke, life-threatening ventricular arrhythmias, and recurrence of angina) and the occurrence of new medical disorders. Secondary outcome measures are the incidence of rehospitalizations due to cardiological problems, the prevalence of patients with New York Heart Association class ≥ II, left ventricular function, as assessed by echocardiography, and mean score of psychometric tests in the two groups at follow-up. Conclusion Our study has been planned to obtain an insight into how a STP influences clinical outcomes after interventional and medical treatment of AMI.

Endothelial progenitor cells in patients with coronary artery disease and left ventricular dysfunction

ObjectivesEndothelial progenitor cells (EPCs) play a key role in maintenance of endothelial integrity and postnatal neovascularization. We verified whether the number of subpopulations of EPCs is different in patients with coronary artery disease (CAD) and normal or impaired left ventricular (LV) function. MethodsSixty-eight consecutive patients (37 men, age 60±18 years) with CAD were studied. All patients underwent quantitative coronary angiography and flow cytometric analysis. ResultsPatients with LV ejection fraction <45% (n=22) were compared with those with normal function (n=46). The two groups had similar age, sex, cardiovascular risk factors, medical therapy, LV dimension, and number of diseased vessels. Patients with LV dysfunction, by study design, were more symptomatic and had a lower LV ejection fraction. The two groups had similar white cell count and mononuclear cells. The absolute number of CD34+ and CD133+ cells was significantly (P<0.05) higher in patients with LV dysfunction as compared with patients with normal function or healthy participants. In contrast, CD14+ cells were significantly (P=0.005) lower in the former patients than in the latter, whereas no significant difference was noted in the number of cells positive for CD105 among groups. ConclusionSubpopulations of EPCs have a discordant behavior in CAD patients with or without LV dysfunction, with cells positive for the endothelial markers CD34 and CD133 being increased and cells that promote vasculogenesis and microvascular development being significantly reduced.

Safety of drug eluting stents in patients on chronic anticoagulation using long‐term single antiplatelet treatment with clopidogrel

Background: Use of triple therapy with aspirin, clopidogrel, and anticoagulants significantly increases bleeding, thus drug eluting stents (DES) are usually avoided in patients requiring anticoagulation. We tested use of DES vs. BMS using a long‐term therapy with clopidogrel only and anticoagulants in this group of patients. Methods: We enrolled 165 consecutive patients, 79 receiving DES (age 67 ± 9 years, 84% with atrial fibrillation) and 86 receiving bare metal stents (BMS) (age 70 ± 11 years, 71% with atrial fibrillation). All patients received aspirin + clopidogrel + oral anticoagulants for 4 weeks, then aspirin was stopped and clopidogrel was continued during the 12‐month follow‐up. Primary end point was the combined incidence of major adverse coronary events and major bleedings. Results: Incidence of the primary endpoint was 10.1% in patients with DES and 26.7% in patients with BMS (P = 0.01). There was a large difference in incidence of target vessel revascularization (8.1% for DES, 23.3% for BMS, P = 0.01), whereas incidence of myocardial infarction (3.8% in DES vs. 8.1% in BMS) and major bleeding (1.3% vs. 2.3%, respectively) were not significantly different. There were no cases of stent thrombosis. On multivariate Cox regression analysis, the only factor associated with a reduced risk of the primary endpoint was use of DES (hazard ratio 0.35 with 95% confidence interval 0.14–0.85, P = 0.02). Conclusions: Results of our cohort study suggest that use of DES associated with a treatment with clopidogrel only may be safe and significantly reduce the need for new revascularization in patients requiring chronic anticoagulation.© 2009 Wiley‐Liss, Inc.

Clinical effects of routine postdilatation of drug‐eluting stents

To assess the clinical effects of postdilatation of drug‐eluting stents (DES).

Core valve implant failure in the presence of mechanical mitral prosthesis: Importance of assessing left ventricular outflow tract

Transcatheter aortic valve replacement in the presence of a mitral prosthetic valve is a technically challenging endeavor. The presence of a mitral prosthesis can alter the geometry of the landing zone for the device. A multi slice computerized tomography with comprehensive review of left ventricular outflow tract and aortic root in its entirety is critical for preventing implant failure. Technical expedients to treat implant failure involve understanding of the device as well its relationship with the mitral prosthesis.

Early beneficial effects of drug-eluting stents in vein grafts wane during long term follow-up: a case-control study.

The aim of the study was to compare outcomes of drug‐eluting stents (DES) versus bare‐metal stents (BMS) in saphenous vein graft (SVG) interventions in a case–control study with a long‐term follow‐up.