Bernard Cassagneau

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...

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.

Postischemic Left Ventricular Dysfunction Is Abolished by Alpha-Adrenergic Blocking Agents

OBJECTIVES We sought to evaluate the efficacy of alpha-adrenergic blocking agents in counteracting left ventricular (LV) dysfunction occurring after transient ischemia in humans. BACKGROUND The mechanisms underlying postischemic LV dysfunction are largely unknown. METHODS Percutaneous transluminal coronary angioplasty (PTCA) provides a clinical model of ischemia and reperfusion. In 50 patients undergoing coronary stenting for 77+/-5% stenosis, LV function was monitored by transesophageal echocardiography during and 30-min after PTCA. Fifteen minutes after stenting, 15 patients received 12 microg/kg body weight of the alpha-blocker phentolamine intracoronarily, 15 patients received 600 microg/kg of the alpha1-blocker urapidil intravenously, 10 patients received the combination of phentolamine and 1.2 mg of propranolol intracoronarily, and 10 patients received saline. RESULTS Fifteen minutes after successful coronary dilation, significant contractile dysfunction occurred in previously ischemic and nonischemic myocardium. LV dysfunction was accompanied by an increase in coronary resistance and diffuse vasoconstriction. Alpha-blockers counteracted LV dysfunction and coronary resistance and the increase in vasoconstriction. Phentolamine and urapidil increased global LV shortening from 34+/-9% to 45+/-8% and to 49+/-8%, respectively (p < 0.05). After the administration of propranolol combined with phentolamine, LV dysfunction remained unchanged (34+/-6%), as in control subjects. CONCLUSIONS LV dysfunction occurs after PTCA, as described in animal models after ischemia. Alpha-blockers abolished LV, macrocirculatory and microcirculatory dysfunction, whereas the alpha-blocker effect was prevented by combining alpha- and beta-blockers. The evidence of diffuse rather than regional dysfunction, together with the opposite effects of alpha- and beta-blockade, supports the hypothesis of neural mechanisms eliciting postischemic LV dysfunction.

Results of stenting of unprotected left main coronary artery stenosis in patients at high surgical risk.

From March 1994 to September 1996, 39 patients underwent stenting of the unprotected left main coronary artery because of high surgical risk. Stenting appeared to improve clinical outcome, but there was a significant mortality rate at long-term follow-up.

Coronary stenting in diabetics: Immediate and mid‐term clinical outcome

Balloon angioplasty in diabetics is associated with acceptable immediate results but with high rates of restenosis, target vessel revascularization, and late mortality. The impact of coronary stenting on the outcome of these patients remains controversial. We reported the immediate and mid‐term clinical outcome of 272 consecutive diabetic patients, representing 12.5% of the population undergoing coronary stenting between May 1995 and April 1997. Diabetes mellitus was insulin‐requiring in 58 patients and non–insulin‐requiring in 214. Stenting performed on large vessels (mean diameter ≥3 mm) was successful in 99.2% of nondiabetic patients and in all cases in diabetics. During in‐hospital stay, the complications rate, including mortality, nonfatal myocardial infarction, emergency coronary bypass surgery, and stent subacute thrombosis, was similar in nondiabetic patients, insulin‐requiring, and non–insulin‐requiring diabetics (2.55%, 0%, and 2.0%, respectively). No complication occurred in the insulin‐requiring group. One patient (0.5%) died from myocardial infarction and another (0.5%) presented a nonfatal myocardial infarction (subacute stent thrombosis) in the non–insulin‐requiring group. The clinical follow‐up (mean length 13 ± 8 months) was obtained in 93% and 97% of the insulin‐requiring and non–insulin‐requiring diabetics, respectively. Overall mortality was significantly higher in insulin‐requiring patients (9.3% vs. 2.4%). Nonfatal myocardial infarction and target lesion revascularization rates were similar in the two groups (0% vs. 0.5% and 8.2% vs. 10.5%). These results suggest that coronary stenting in diabetics could be performed with acceptable immediate and mid‐term results. Cathet. Cardiovasc. Intervent. 47:279–284, 1999.

Nine-year follow-up of balloon-expandable Palmaz-Schatz stent in patients with single-vessel disease.

The long‐term effects of intracoronary stents in human are unknown. This is the first 9‐year follow‐up report of single‐vessel‐disease patients treated with the Palmaz‐Schatz stent. Between March and December 1989, out of the 107 patients undergoing Palmaz‐Schatz stent implantation, 71 (66%) had single‐vessel disease. The average age of these patients was 58 ± 9 years and 79% were men. At 9 years, follow‐up was obtained for 90.1% and major adverse clinical events consisted of 4 deaths giving a global survival rate of 95.8%, 7 myocardial infarction, 3 bypass surgeries, and 16 repeat percutaneous revascularization procedures. The 9‐year event‐free survival rate was 60%, and 81.7% of the patients were free from death, myocardial infarction, and bypass surgery. Multivariate analysis showed that the only predictive factor of major adverse clinical events was the presence of diabetes mellitus (P < 0.004). Cathet. Cardiovasc. Intervent. 50:170–174, 2000.