Irene Bossi

α-Adrenergic Blockade Improves Recovery of Myocardial Perfusion and Function After Coronary Stenting in Patients With Acute Myocardial Infarction

Background—AMI reperfusion by thrombolysis does not improve TIMI flow and LV function. The role of infarct-related artery (IRA) stenosis and superimposed changes in coronary vasomotor tone in maintaining LV dysfunction must be elucidated. Methods and Results—Forty patients underwent diagnostic angiography 24 hours after thrombolysis. Seventy-two hours after thrombolysis, the culprit lesion was dilated with coronary stenting. During angioplasty, LV function was monitored by transesophageal echocardiography. Percent regional systolic thickening was quantitatively assessed before PTCA, soon after stenting, 15 minutes after stenting, and after phentolamine 12 μg/kg IC (n=10), the α1-blocker urapidil 600 μg/kg IV (n=10), or saline (n=10). Ten patients pretreated with β-blockers received urapidil 10 mg IC. Coronary stenting significantly improved thickening in IRA-dependent and in non–IRA-dependent myocardium (from 27±15% to 38±16% and from 40±15% to 45±15%, respectively). Simultaneously, TIMI frame count decre...

Unprotected left main coronary artery stenting: correlates of midterm survival and impact of patient selection.

BACKGROUND The study served to present the in-hospital and six-month clinical outcome and also the long-term survival data of a consecutive series of patients undergoing stenting for unprotected left main coronary artery (LMCA) disease. METHODS Revascularization with coronary bypass surgery has been generally recommended for treatment of left main coronary stenosis. Improvements in angioplasty and coronary stent techniques and equipment may result in the wider applicability of a percutaneous approach. A total of 92 consecutive patients underwent unprotected LMCA stenting between March 1994 and December 1998. For the initial 39 patients (group I) angioplasty was performed only when surgical revascularization was contraindicated. The remaining 53 patients (group II) also included patients in whom surgery was feasible. Patients were followed for 7.3 +/- 5.8 months (median 239 days; range 49 to 1,477 days). RESULTS Compared to group I, group II patients had higher left ventricular ejection fraction (60 +/- 12% vs. 51 +/- 16%, p < 0.01), less severe LMCA stenosis (68 +/- 12% vs. 80 +/- 10%, p < 0.001), lower surgical risk score (13 +/- 7 vs. 20 +/- 7, p < 0.001), and had angioplasty more often performed via the radial approach (88% vs. 23%, p < 0.001) with smaller guiding catheters (6F: 49% vs. 15%; 8F: 2% vs. 77%, p < 0.001). The procedural success rate was 100%. In-hospital mortality was 4% (4 deaths, 3 cardiac). During follow-up there were six deaths, 13 patients required repeat percutaneous transluminal coronary angioplasty (4 LMCA), and two required coronary artery bypass graft surgery. Estimated survival (+/- SEE) was 89 +/- 6.3% at 500 days and 85 +/- 12% at 1,000 days post-stenting. Overall mortality was 3.8% in group II and 20.5% in group I (p < 0.02). CONCLUSIONS Coronary stenting can be performed safely in high-risk individuals with acceptable intermediate-term outcome. It may be feasible to broaden the application of this technique in selected patients needing revascularization for left main coronary disease.

Ticlopidine and aspirin pretreatment reduces coagulation and platelet activation during coronary dilation procedures.

OBJECTIVES It is unknown whether a therapeutic combination of aspirin (ASA) and ticlopidine might effectively decrease activation of hemostasis. BACKGROUND Percutaneous transluminal coronary angioplasty (PTCA), rotational atherectomy and stent implantation are procedures that fracture or ablate endothelium and plaque, a situation that activates hemostasis. METHODS In 85 patients undergoing PTCA for a 77.8 +/- 1% stenosis, we measured markers of coagulation and platelet activation (thrombin-antithrombin complexes [TAT], prothrombin fragment 1 + 2 [F1 + 2] serotonin and the presence of circulating activated platelets reacting with monoclonal antibodies against glycoproteins exposed on platelet membranes). Blood samples were drawn from a peripheral vein and from the coronary ostium before the procedures. Both immediately and 10 min after angioplasty, and 10 min afterward, samples were collected from a probing catheter (0.018 in, [0.46 cm]) positioned beyond the stenosis. All patients were being treated with antianginal drugs and ASA, 250 mg/day. Seventy of them had taken ticlopidine, 250 mg, twice daily for < or = 1 day (< or = 24 h) (n = 28) or for > or = 3 days (> or = 72 h) (n = 42). Heparin (150 U/kg) was administered before angioplasty. Thirty patients underwent PTCA; 15 of them were not treated with ticlopidine and 15 were given ticlopidine (> or = 72 h). Thirty-five patients had stent implantation, 20 rotational atherectomy. RESULTS Before and during the procedures, there was greater thrombin generation (expressed by higher TAT and F1 + 2 plasma levels) in patients not taking ticlopidine or taking it for < or = 24 h (p < 0.05). Platelet activation and plasma serotonin levels were also significantly higher in the no ticlopidine or < or = 24-h ticlopidine groups. CONCLUSIONS The combined use of ticlopidine, ASA and heparin effectively controls activation of coagulation in patients with stable or unstable angina undergoing coronary dilation.

In-stent restenosis: long-term outcome and predictors of subsequent target lesion revascularization after repeat balloon angioplasty

OBJECTIVES We sought to evaluate the long-term clinical outcome of patients undergoing successful balloon angioplasty for in-stent restenosis, and to determine correlates of the need for subsequent target lesion revascularization (TLR). BACKGROUND In-stent restenosis can be safely treated by repeat percutaneous intervention. Reported subsequent TLR rates have varied from 20% to 80% and seem related to the type of restenotic lesion. METHODS The study population comprised 234 patients with follow-up data who were successfully treated with repeat balloon angioplasty for in-stent restenosis in 257 lesions between May 1995 and January 1998 at our institution. RESULTS Clinical follow-up was available at 459 (286 to 693) days after the repeat procedure. Event-free survival was 78.5% and 74.6% at 12 and 24 months, respectively. Recurrent events occurred in 58 patients (24.8%), including 6 deaths (2.6%), 4 myocardial infarction (1.7%) and repeat target vessel revascularization in 50 patients (21.4%). Independent predictors of repeat TLR were time to in-stent restenosis <90 days (Hazard ratio 4.67, p < 0.001), minimal luminal diameter after repeat procedure (Hazard ratio 0.38, p = 0.034) and the angiographic pattern of in-stent restenosis (Hazard ratio 1.65, p = 0.036). CONCLUSIONS Balloon angioplasty is an effective means of treating in-stent restenosis. The long-term results are acceptable particularly for focal restenotic lesions. Further restenosis is more common in patients with early initial recurrence, more proliferative lesions and a poorer angiographic result from repeat angioplasty.

Effects of Selective α1- and α2-Adrenergic Blockade on Coronary Flow Reserve After Coronary Stenting

BACKGROUND Coronary flow reserve (CFR) is not normalized shortly after coronary stenting. We hypothesized that alpha-adrenergic coronary vasoconstriction acts to limit CFR. METHODS AND RESULTS We assessed flow velocity by Doppler wires and cross-sectional area by angiography in 46 patients undergoing coronary culprit lesion stenting (81+/-4% stenosis). Hyperemia was induced by adenosine (24 micro g IC or 140 micro g/kg per minute IV) before and after stenting. Finally, either the alpha(1)-antagonist urapidil (10 mg IC) or the alpha(2)-antagonist yohimbine (3 mg IC) was randomly combined with adenosine. In 8 subjects with angiographically normal coronary arteries, CFR was increased from 3.21+/-0.30 to 3.74+/-0.43 by yohimbine and to 4.58+/-0.65 by urapidil, respectively (P=0.0001). Patients were divided according to the cutoff of CFR > or =3.0 (n=18) or <2.5 (n=28). Revascularization per se did not change CFR. However, 15 minutes after stenting, CFR decreased to 2.05+/-0.55 from CFR 3.64+/-0.58, whereas in patients with CFR 2.39+/-0.51, it remained unchanged. Yohimbine improved CFR to 3.26+/-0.42 and to 3.41+/-0.58 in patients with >3.0 and <2.05+/-0.55 baseline CFR, respectively. Urapidil improved CFR to 3.52+/-0.30 and 3.98+/-1.07, respectively. CONCLUSIONS Urapidil and yohimbine attenuated the CFR impairment occurring after revascularization by increasing both the epicardial vasodilator effect of adenosine and the blood flow velocity, thus suggesting that the adrenergic system plays an important role in limiting the capacity of the coronary circulation to dilate.

Increased concentrations of inflammatory mediators in unstable angina: correlation with serum troponin T

OBJECTIVE To measure plasma interferon γ, monocyte chemotactic protein-1 (MCP-1), and interleukin 6 and to assess their correlation with cardiac troponin T in unstable angina. DESIGN Blood sampling in patients undergoing coronary arteriography for known or suspected ischaemic heart disease. PATIENTS 76 patients divided in three groups: 29 with unstable angina (group 1), 28 with stable angina (group 2), and 19 without ischaemic heart disease and with angiographically normal coronary arteries (group 3). MAIN OUTCOME MEASURES Plasma interleukin 6, interferon γ, MCP-1, and troponin T in the three groups of patients. RESULTS Interleukin 6 was increased in group 1 (median 2.19 (range 0.53–50.84) pg/ml) compared with the control group (1.62 (0.79–3.98) pg/ml) (p < 0.005), whereas interferon γ was higher in group 1 (range 0–5.51 pg/ml) than in the other two groups (range 0–0.74 pg/ml and 0–0.37 pg/ml; p < 0.005 and p < 0.001, respectively). Patients with unstable angina (group 1) and positive troponin T had higher concentrations of interferon γ than those with negative troponin T (0–5.51 pg/mlv 0–0.60 pg/ml, p < 0.001). Plasma MCP-1 was also higher in group 1 (median 267 (range 6–8670) pg/ml) than in the other two groups (134 (19–890) pg/ml and 84.5 (5–325) pg/ml; p < 0.005 and p < 0.001, respectively), and among group 1 patients with a positive troponin T assay than in those with normal troponin T (531 (14.5–8670) pg/mlv 69 (6–3333) pg/ml; p < 0.01). There was no difference in plasma interleukin 6 in group 1 patients between those with and without raised troponin T. CONCLUSIONS The inflammatory cytokines interferon γ and MCP-1 are increased in patients with unstable angina, particularly in those with raised concentrations of troponin T, suggesting that they are probably related to myocardial cell damage or to plaque rupture and thrombus formation.

Long-term clinical outcome after endoluminal reconstruction of diffusely degenerated saphenous vein grafts with less-shortening wallstents.

OBJECTIVES This study was designed to evaluate the immediate and long-term clinical results of patients undergoing endoluminal reconstruction in diffusely degenerated saphenous vein grafts (SVGs) with elective implantation of one or more less-shortening Wallstents. BACKGROUND The optimal treatment strategy for patients with diffusely degenerated SVGs is controversial. Endoluminal reconstruction by stent implantation is one proposed strategy; however, there are few data regarding long-term clinical outcome. METHODS Between May 1995 and September 1998, 6,534 consecutive patients underwent angioplasty in our institution, including 440 who were treated for SVG lesions. Of these, 126 (115 men, 11 women, median age 69.5 years, range: 33-86 years) with old SVGs (mean age: 13+/-5 years) diffusely degenerated stenosed or occluded (mean lesion length: 27+/-12 mm) were treated electively with implantation of one or multiple (total 197) less-shortening Wallstents. RESULTS Before discharge, 13 patients (10.3%) sustained at least one major cardiovascular event, including 4 deaths (3.2%), 11 myocardial infarctions (MI) (8.7%), and 3 repeat revascularizations (target vessel = 1, nontarget vessel = 2, 2.4%). Surviving patients were followed for 22+/-11 months: 13 patients (11.1%) died, 11 (9.4%) sustained an MI, 37 underwent angioplasty (31.6%), and 4 (3.4%) underwent bypass surgery. The estimated three-year event-free survival rates (freedom from death, and freedom from death/MI/target vessel revascularization) were (mean +/- SE) 81.1+/-7.8% and 43.2+/-18.5%, respectively. CONCLUSIONS The long-term clinical outcome of patients undergoing endoluminal reconstruction in diffusely degenerated SVG is relatively poor, mainly because of a high incidence of death or MI and the frequent need for repeat angioplasty. It is unlikely that percutaneous intervention alone will provide a satisfactory or definitive solution for these patients.

Stent thrombosis: Incidence and related factors in the R.I.S.E. registry (Registro Impianto Stent Endocoronarico)

Although stent thrombosis has been greatly reduced by adequate stent expansion with high‐pressure balloon inflations and by the use of antiplatelet drugs, this event is still frightening, as it may lead to acute myocardial ischemia resulting in acute myocardial infarction or sudden death. Therefore, the definition of factors associated with stent thrombosis may provide a better understanding of the mechanisms underlying this phenomenon and may permit us to define therapeutic strategies to further reduce its occurrence. The purpose of this study was to assess factors responsible for the occurrence of stent thrombosis after coronary stent implantation in 939 consecutive patients enrolled in the Registro Impianto Stent Endocoronarico (R.I.S.E. Study Group). Consecutive patients undergoing coronary stent implantation at 16 medical centers in Italy were prospectively enrolled in the registry. Clinical data, and qualitative and quantitative angiographic findings were obtained from data collected in case report forms at each investigator site. The study group consisted of 781 men and 158 women with a mean age of 59 yr: 1,392 stents were implanted in 1,006 lesions and expanded at a maximal inflation pressure of 14.7 ± 3 atm. The great majority of patients (92%) received only antiplatelet drugs after coronary stenting. During hospitalization there were 45 major ischemic complications in 39 patients (4.2%): 13 events were related to acute or subacute thrombosis (1.4%). Another stent thrombotic event occurred in the first month of follow‐up. On multivariate logistic regression analysis, stent thrombosis was related to the following factors: unplanned stenting (OR 3.46, 95% CI 1.65–7.23), unstable angina (OR 3.37, 95% CI 1.11–10.14) and maximal inflation pressure (OR 0.83 , 95% CI 0.75–0.93). In conclusion, this registry shows that in an unselected population of patients undergoing coronary stenting, stent thrombosis occurs in less than 2% of patients and is significantly related to unplanned stent implantation, unstable angina, and maximal inflation pressure. The incidence of this phenomenon is likely to be further reduced by the use of new potent antiplatelet drugs, such as platelet glycoprotein IIb/IIIa antagonists. Cathet. Cardiovasc. Intervent. 46:13–18, 1999.

Aspirin Desensitization in Patients With Coronary Artery Disease

Background— There are limited data on aspirin (ASA) desensitization for patients with coronary artery disease. The aim of the present study was to assess the safety and efficacy of a standard rapid desensitization protocol in patients with ASA sensitivity undergoing coronary angiography. Methods and Results— This is a prospective, multicenter, observational study including 7 Italian centers including patients with a history of ASA sensitivity undergoing coronary angiography with intent to undergo percutaneous coronary intervention. A total of 330 patients with history of ASA sensitivity with known/suspected stable coronary artery disease or presenting with an acute coronary syndrome, including ST-segment–elevation myocardial infarction were enrolled. Adverse effects to aspirin included urticaria (n=177, 53.6%), angioedema (n=69, 20.9%), asthma (n=65, 19.7%), and anaphylactic reaction (n=19, 5.8%). Among patients with urticaria/angioedema, 13 patients (3.9%) had a history of idiopathic chronic urticaria. All patients underwent a rapid ASA (5.5 hours) desensitization procedure. The desensitization procedure was performed before cardiac catheterization in all patients, except for those (n=78, 23.6%) presenting with ST-segment–elevation myocardial infarction who underwent the desensitization after primary percutaneous coronary intervention. Percutaneous coronary intervention was performed in 235 patients (71%) of the overall study population. The desensitization procedure was successful in 315 patients (95.4%) and in all patients with a history of anaphylactic reaction. Among the 15 patients (4.6%) who did not successfully respond to the desensitization protocol, adverse reactions were minor and responded to treatment with corticosteroids and antihistamines. Among patients with successful in-hospital ASA desensitization, 253 patients (80.3%) continued ASA for at least 12 months. Discontinuation of ASA in the 62 patients (19.7%) who had responded to the desensitization protocol was because of medical decision and not because of hypersensitivity reactions. Conclusions— A standard rapid desensitization protocol is safe and effective across a broad spectrum of patients, irrespective of the type of aspirin sensitivity manifestation, with indications to undergo coronary angiography with intent to perform percutaneous coronary intervention. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT02848339.

Effect of aspirin and ticlopidine on plasma tissue factor levels in stable and unstable angina pectoris

Patients with unstable angina have an increased activation of the coagulation system. Aspirin and ticlopidine given in combination may potentiate each other by the combination of different action mechanisms and may reduce the risk of coronary occlusion and clinical instability. Plasma tissue factor (TF) levels collected into the stenotic coronary artery may be an index of TF expression within the vasculature. In 160 patients undergoing angioplasty for a 81+/-5% coronary lesion, we measured TF in blood samples collected from a vein and from the coronary ostium. Immediately after and 10 minutes after the dilation procedures the samples were withdrawn also beyond the lesion. Heparin 150 U/kg was given as an anticoagulant. All patients were pretreated with 250 mg/day of aspirin. One hundred twenty patients were randomly assigned to receive 24, 48, or 72 hours of ticlopidine treatment (250 mg/twice daily). TF levels did not increase during angioplasty but there was a significantly higher TF expression in unstable than in stable patients, irrespective of the invasiveness of debulking procedures. When ticlopidine was given for 72 hours, TF levels were similar to normal laboratory values both in stable and unstable patients. This combined antiplatelet pretreatment may be of benefit in unstable angina patients, with a favorable cost/benefit ratio.