Biomedical subjects
Publications and source records attributed to J M Lablanche.
This report describes the case of a 67-year-old man in whom atrial right-to-left shunt developed after a right pneumonectomy, leading to dyspnea with severe arterial desaturation. Transcatheter occlusion of the patent foramen ovale was successfully performed using a buttoned device. Review of literature and mechanisms of these atrial right-to-left shunts are discussed.
OBJECTIVES: This study sought to determine whether pravastatin affects clinical or angiographic restenosis after coronary balloon angioplasty. BACKGROUND: Experimental data and preliminary clinical studies suggest that lipid-lowering drugs might have a beneficial effect on restenosis after coronary angioplasty. METHODS: In a multicenter, randomized, double-blind trial, 695 patients were randomized to receive pravastatin (40 mg/day) or placebo for 6 months after successful balloon angioplasty. All patients received aspirin (100 mg/day). The primary angiographic end point was minimal lumen diameter (MLD) at follow-up, assessed by quantitative coronary angiography. A sample size of 313 patients per group was required to demonstrate a difference of 0.13 mm in MLD between groups (allowing for a two-tailed alpha error of 0.05 and a beta error of 0.20). To allow for incomplete angiographic follow-up (estimated lost to follow-up rate of 10%), 690 randomized patients were required. Secondary end points were angiographic restenosis rate (restenosis assessed as a categoric variable, > 50% stenosis) and clinical events (death, myocardial infarction, target vessel revascularization). RESULTS: At baseline, clinical, demographic, angiographic and lipid variables did not differ significantly between groups. In patients treated with pravastatin, there was a significant reduction in total and low density lipoprotein cholesterol and triglyceride levels and a significant increase in high density lipoprotein cholesterol levels. At follow-up the MLD (mean +/- SD) was 1.47 +/- 0.62 mm in the placebo group and 1.54 +/- 0.66 mm in the pravastatin group (p = 0.21). Similarly, late loss and net gain did not differ significantly between groups. The restenosis rate (recurrence > 50% stenosis) was 43.8% in the placebo group and 39.2% in the pravastatin group (p = 0.26). Clinical restenosis did not differ significantly between groups. CONCLUSIONS: Although pravastatin has documented efficacy in reducing clinical events and angiographic disease progression in patients with coronary atherosclerosis, this study shows that it has no effect on angiographic outcome at the target site 6 months after coronary angioplasty.
OBJECTIVE: To analyse the potential association of the angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) gene polymorphisms on left ventricular function and mass in patients with normal coronary arteries. DESIGN: Consecutive sample. SETTING: University hospital. SUBJECTS: 141 consecutive white patients referred for coronary angiography and with angiographically normal coronary arteries. Patients with valvar diseases, cardiomyopathies, or a history of myocardial infarction were excluded. MAIN OUTCOME MEASURES: Left ventricular variables were measured for all patients. The ACE and AT1R genotypes were determined with a polymerase chain reaction based protocol using DNA prepared from white blood cells. A general linear model was used to compare data according to the ACE and to the AT1R genotypes. RESULTS: A strong association was observed between left ventricular mass and systemic hypertension (mean (SD) hypertension: 114 (31) g/m2; no hypertension 98 (23) g/m2; P < 0.003). However, no influence of ACE and AT1R polymorphisms on left ventricular mass was found, regardless of systemic hypertension. The subjects homozygous for the AT1R CC mutation had a significantly lower ejection fraction than those with allele A (AC+AA) (mean (SD) 62(12)% and 68(10)%, respectively, P < 0.05). No synergistic interaction of ACE and AT1R gene polymorphisms on left ventricular function and mass was found. CONCLUSIONS: These data do not support an association of the ACE and AT1R genotypes on left ventricular hypertrophy in white patients with normal coronary arteries.
In animal models, a hypercholesterolemic diet induces areas of deendothelialization and impairs endothelium-dependent vasorelaxation. Angiogenic growth factors increase endothelial cell growth in vivo. This study was thus designed to test the hypothesis that chronic administration of basic fibroblast growth factor (bFGF) in hypercholesterolemic rabbits might restore normal physiological responses to endothelium-dependent agonists. After feeding on a 2% cholesterol diet for 6 wk, 14 New Zealand White rabbits received twice-weekly intravenous boluses of either 2.5 microg bFGF (hypercholesterolemic bFGF group, n = 6) or placebo (hypercholesterolemic control group, n = 8) for 3 wk and were killed for assessment of in vitro vasoreactivity and for histological analysis. Six animals fed with standard rabbit diet were used to assess normal responses. Endothelium-dependent responses to acetylcholine and to the calcium ionophore A-23187 were reduced in the hypercholesterolemic control group compared with normal rabbits. Hypercholesterolemic animals treated with bFGF had significantly better endothelium-dependent responses than hypercholesterolemic rabbits not treated with bFGF. Endothelium-independent responses did not differ significantly among the three groups. A similar degree of plaque formation was observed in control- and bFGF-treated hypercholesterolemic rabbits. These results show that, in this model of atherosclerosis, bFGF has a highly beneficial effect on the functional responses of atherosclerotic vessels and does not have a deleterious effect on the degree of plaque formation.
Coronary angioscopy evaluates the composition of the atherosclerotic plaque by direct examination of the arterial wall. The angioscope is fitted with a balloon which prevents assessment of the proximal segment of the vessels. The fibre optic system provides and excellent view of the mid and distal segments of the coronary arteries. The coronary arteries appear smooth and white on angioscopy. The atherosclerotic plaque is a white or yellowish incursion. Unstable plaques are characterised by the presence of thrombus. In unstable angina, thrombus is observed in 64% of cases and in 75% of cases during the first month after myocardial infarction. The colour of the plaque seems to be related to its fragility: the yellow plaque is much more common during myocardial infarction than in unstable angina (75% versus 47% of cases). Finally, after coronary angioplasty restenosis is more commonly white, covered by neo-intimal proliferation. Angioscopy has been shown to be feasible and safe and it is a better method of identifying thrombus. At present, it is a tool for clinical research in coronary thrombosis and interventional cardiology.
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Restenosis remains the principal limitation of coronary angioplasty; its main mechanisms are neointimal hyperplasia and vascular remodeling. The endothelium destroyed at angioplasty will progressively recover the denuded zone. However, dysfunction of this neo-endothelium persists for quite a period and may participate in restenosis by influencing these two components (hyperplasia and remodeling). Several therapeutic strategies are under evaluation to try and accelerate the regeneration of the endothelium and make it functional more rapidly. Increasing available nitric oxide (NO) decreases the hyperplasia and improves endothelial function. Growth factors accelerate the endothelial regeneration and improves its function: the effect on hyperplasia depends on the growth factor used. The angiotensin converting enzyme inhibitors decrease hyperplasia by improving endothelial function. These therapeutic strategies merit evaluation in the clinical setting.
The restenosis and reocclusion rate after coronary recanalization by conventional angioplasty are high. The role of stent implantation in this context is unknown. The authors assessed a group of 49 patients who underwent implantation of one or more stent after a recanalization procedure by angiography at 6 months. The restenosis rate assessed by quantitative angiography was 24%; no cases of reocclusion were observed. These angiographic results were accompanied with a significant improvement of the anginal symptoms (p < 0.01). These results suggest that stent implantation following recanalization of a coronary occlusion may be beneficial on the restenosis and reocclusion rates and anginal symptoms. However, they should be confirmed by randomised study. It would also be important to analyse the impact of this procedure on the outcome of left ventricular function.
In this study, restenosis after coronary angioplasty is evaluated in a series of 291 consecutive patients according to ACE genotypes. The authors conclude that the ACE 2ID polymorphism has no effect on progressive restenosis after balloon angioplasty, but it is implicated in a distinct mechanism of restenosis (thrombosis and occlusion) that could explain discrepancies among previously published studies.
BACKGROUND: After experimental angioplasty, partial or complete reendothelialization of the denuded surface occurs; the function of the regenerated endothelium has, however, been shown to be abnormal. Basic fibroblast growth factor (bFGF) is mitogenic for endothelial cells in vitro and in vivo. We investigated whether chronic administration of bFGF in a rabbit model of balloon denudation might not only improve endothelial regrowth but also restore normal physiological responses to endothelium-dependent agonists. METHODS AND RESULTS: Thirty-nine New Zealand White rabbits underwent balloon denudation of the right iliac artery. Twenty rabbits received intravenous administration of bFGF (2.5 micrograms twice a week for 2 weeks). Nineteen rabbits receiving saline injections served as controls. Animals were killed on day 28 for assessment of reendothelialization and neointimal thickening and for analysis of in vitro vasoreactivity. Animals in the bFGF group had a significantly (P<.005) greater degree of reendothelialization than controls (115 +/- 13 versus 55 +/- 6 mm2). Neointimal thickening was similar in the two groups. Four weeks after denudation, endothelium-independent responses did not differ significantly between the two groups. In contrast, the maximal endothelium-dependent acetylcholine-induced relaxation of the bFGF-treated animals (Emax, 40 +/- 7%) was significantly greater than that of the control group (Emax, 11 +/- 9%; P<.05). CONCLUSIONS: Systemic administration of bFGF restores, in large part, the responses of previously denuded arterial segments to endothelium-dependent vasodilators. Angiogenic growth factors may help to reestablish normal endothelial cell function in patients who have undergone angioplasty.
OBJECTIVE: To describe the morphological changes occurring in the months following percutaneous transluminal coronary angioplasty (PTCA) of unstable plaques. BACKGROUND: Coronary angioscopy is a relatively new technique to assess plaque morphology. Previous angioscopic studies have shown that unstable coronary lesions are characterized by complex morphology, evidence of plaque rupture, and intraluminal thrombi. No serial angioscopic studies have investigated the effects of PTCA on plaque morphology at such lesions. METHODS: We studied 15 patients who underwent successful PTCA for an unstable coronary syndrome (unstable angina: n = 5; recent myocardial infarction: n = 10). Angioscopy was performed immediately before PTCA in 14 patients, immediately after PTCA in 13 patients, and at follow-up (225 +/- 62 days after PTCA) in all patients. RESULTS: Pre-PTCA, plaque morphology was defined as complex in 18%, ulcerated in 27%; the vessel was totally occluded in 18% of cases. Plaque colour was yellow in 75% of patients. A thrombus was identified at the lesion site in 71% of patients. Immediately post-PTCA, small surface disruptions and dissections were observed in 62% of patients. Plaque colour was yellow in 85% of cases. Seventy-seven percent of patients had an angioscopically visible thrombus at the PTCA site. At follow-up, however, plaque shape was almost uniformly classified as smooth concentric (93%); plaque colour was white in 93%; no thrombus was observed. CONCLUSIONS: These results demonstrate the healing of unstable plaques in the months following PTCA. The angioscopic appearance at 6 months is that of a stable plaque (smooth concentric, white, without thrombus). Whether this stable angioscopic appearance predicts long-term clinical stability remains to be determined.
OBJECTIVES: We hypothesized that percutaneous transluminal coronary angioplasty performed on coronary stenoses that have demonstrated rapid angiographic progression would be associated with a high risk of restenosis. BACKGROUND: High rates of restenosis have been documented after percutaneous transluminal coronary angioplasty of unstable lesions and of lesions that recur rapidly after a successful initial angioplasty. This suggests that the "activity' of the plaque at the time of angioplasty may be an important factor determining the risk of restenosis. METHODS: In our institution we recommend angiographic follow-up for all patients with successful percutaneous transluminal coronary angioplasty. In this way we identified 86 consecutive patients who, at the time of angiographic follow-up had not developed restenosis at the dilated site, but required a further percutaneous transluminal coronary angioplasty at a different site. (which was successful). Based on quantitative angiographic measurements, 45 of these lesions (rapidly progressive lesions) had significantly increased in severity in the interval between the two angiograms (7.7 +/- 3.3 months) while 41 (stable lesions) had not. Rapid progression was defined as a > 0.4 mm decrease in minimal lumen diameter between initial angiography and percutaneous transluminal coronary angioplasty. All 86 patients had further angiographic follow-up 6 months later. RESULTS: Baseline clinical and angiographic variables were similar in both groups except that a higher proportion of patients in the rapid progression group had unstable angina (20% vs 5%; P < 0.05). Late loss during follow-up did not differ statistically between groups (0.31 mm) and minimal lumen diameter at follow-up was also similar (stable lesion group = 1.40 +/- 0.48 mm; rapidly progressive lesion group = 1.30 +/- 0.59 mm). The loss index (late loss divided by acute gain) was also similar in both groups (0.45 +/- 0.52 in the stable lesion group, 0.37 +/- 0.76 in the rapidly progressive lesion group). A strong correlation between acute gain and late loss was observed in the stable lesion group (r = 0.61; P < 0.0001); by contrast, there was no relationship between these two variables in the rapidly progressive lesion group (r = 0.20; P = 0.19). CONCLUSIONS: Percutaneous transluminal coronary angioplasty in patients with unstable angina or with early recurrence after a first percutaneous transluminal coronary angioplasty is associated with an increased risk of restenosis. By contrast, this study shows that angiographic instability, as evidenced by rapid stenosis progression, has no deleterious effect on the occurrence of restenosis. Percutaneous transluminal coronary angioplasty thus appears as a reasonable therapeutic option for coronary stenoses that have demonstrated rapid angiographic progression in the months prior to the procedure.
OBJECTIVE: Multiple studies have been designed to analyse restenosis angiographically but few have studied the vasoreactivity of coronary segments subjected to angioplasty a few months before. In the present study we analysed, with use of quantitative angiography, the vasoreactivity of previously dilated segments to graded doses of ergonovine and of isosorbide dinitrate. PATIENTS: Fifty consecutive patients undergoing follow-up angiography 6 months after a single coronary angioplasty procedure were studied. RESULTS: The vasoconstrictor response at dilated segments (-19.3 +/- 3.0%) was significantly greater than at control proximal and distal sites in dilated (-7.3 +/- 1.1%, -11.0 +/- 2.9%) and non-dilated (-9.1 +/- 1.3%, -8.3 +/- 2.2%) vessels for the lowest dose of ergonovine (100 micrograms). The constrictor response to 100 micrograms ergonovine (-20.2 +/- 5.3%) at restenosed segments (> 50% stenosis, n = 18) was similar to that (-18.8 +/- 3.8%) at non-restenosed sites (n = 32). In contrast, the degree of constrictor response was similar in all segments including dilated segments for the highest dose of ergonovine used. All segments dilated significantly after intracoronary injection of isosorbide dinitrate. CONCLUSION: Our results demonstrate hypersensitivity of the dilated site to ergonovine 6 months after angioplasty at both restenosed and non-restenosed sites. This response may reflect partial dysfunction of endothelium that has regenerated after injury or hypersensitivity of vascular smooth muscle cells at the site of arterial injury.
Intravascular metallic stents are increasingly used in the non-surgical management of coronary atherosclerosis. Despite intensive anticoagulation, subacute stent thrombosis, which usually has serious clinical consequences, and major haemorrhagic complications remain major problems after stent implantation. In addition, conventional management with anticoagulant therapy requires prolonged hospitalization. In a prospective multicentre study, we investigated the efficacy of a combination of two antiplatelet agents, ticlopidine 500 mg daily and aspirin 200 mg daily, without oral anticoagulation after stent implantation. Since November 1993, 529 consecutive patients, in whom 545 vessels were successfully stented with conventional (non-heparin coated) stents have been enrolled. Stenting was performed as a bailout procedure for failed angioplasty in 112 patients, for a suboptimal result after angioplasty in 314 patients, and electively in the remaining 103 patients. Coronary events related, or possibly related, to stent thrombosis occurred in 5.4% of patients stented as a bailout procedure and in 1.8% of patients stented for a suboptimal result. Serious bleeding complications occurred in 5.4% of patients stented as a bailout procedure and 1.5% of patients stented for a suboptimal result. Neither stent thrombosis nor serious bleeding complications were seen in patients stented electively. Ticlopidine therapy was discontinued in 1.9% of patients due to neutropenia (0.6%) or rash (1.3%). Mean hospital stay decreased from 6.16 +/- 2.14 days to 4.2 +/- 2.15 days during the study period. A combination of two antiplatelet agents can be employed in the vast majority of patients after coronary stent implantation. Subacute stent thrombosis rates and bleeding complications compare favourably with those reported using conventional therapy and the duration of hospitalization is reduced.
Percutaneous transluminal coronary angioplasty (PTCA) is today a procedure of choice in many patients with atherosclerotic coronary artery disease. Despite high rates of initial success, restenosis, occurring in 30 to 40 percent of patients within the first six months, remains the major problem limiting the long-term efficacy of the procedure. Animal models have enhanced our knowledge in the understanding of the mechanisms involved in the restenotic process after experimental angioplasty. In fact, the two known determinants of restenosis are the proliferative and migrative response of underlying smooth muscle cells with production of extracellular matrix and the recently highlighted vascular remodeling. Endothelium, which regenerates from the leading edge of the de-endothelialized area within the weeks following arterial injury, is of particular interest in the modulation of the healing process after the procedure. Endothelial dysfunction, as an imbalance between relaxing and contracting factors, between anti- and pro-coagulant mediators or growth-inhibiting and growth-promoting factors, occurs at sites of regenerating endothelium. Experimental studies, using drugs that enhance endothelium-derived relaxing factors release or drugs that diminish endothelium-derived contracting factors production, have often been shown to be effective in the restenosis prevention. Thus, impairment in endothelial cell function may be considered as one of the major regulatory element in the restenotic process. This review discusses the interactions between endothelial and smooth muscle cells and has for aim to point out the major role of endothelial cells in the development of neointimal thickening and arterial remodeling.
Angiotensin-converting enzyme (ACE) inhibitors reduce intimal hyperplasia after balloon injury. A role for nitric oxide (NO) has been suggested in this effect. Because recent data suggest that NO may modulate some features of endothelial cells and because endothelial cells are involved in the control of intimal hyperplasia, we investigated the role of NO synthesis in the effect of an ACE inhibitor, perindopril, on neoendothelial dysfunction and intimal hyperplasia in a rabbit model of unilateral iliac balloon injury. New Zealand White male rabbits received placebo, perindopril, or cotreatment with perindopril and NG-nitro-L-arginine methyl ester (L-NAME) and were evaluated 4 wk after the injury. Fifteen rabbits (5 in each group) were used to assess in vitro vasoreactivity and twenty-four (8 in each group) for morphometric analysis. In injured vessels, neoendothelium-dependent relaxation in ACE inhibitor-treated animals was improved compared with placebo (P < 0.05) and restored to the level of noninjured vessels (NS). The improvement observed with ACE inhibitor was abolished by cotreatment with L-NAME (P < 0.05). In the same vessels, no effect was observed on neoendothelium-independent vasoreactivity. The improved neoendothelial dysfunction with ACE inhibitor was associated with a 66% reduction in intimal thickening (P < 0.01). The effect was also reversed by cotreatment with L-NAME (P < 0.01). In noninjured vessels, treatment did not alter vasoreactivity or morphology of the vessel wall. These results suggest that NO synthesis may play a key role in the improvement of vascular function seen with ACE inhibitor in balloon-injured vessels.
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The authors undertook a retrospective study of medium-term coronary angiographic controls of a group (Gr) of patients (pts) who had undergone coronary angioplasty for rapidly progressive lesions, to determine whether the rate of progression of a coronary stenosis before angioplasty affected the risk of restenosis. 89 pts underwent primary angioplasty with absence of restenosis at 6 months, but required another angioplasty for another lesion. Angiographic follow-up after the 2nd procedure was performed in 86 pts (96%). The coronary lesion dilated at the 2nd angioplasty procedure was analysed quantitatively with four measurements: one immediately before angioplasty, one after, one at the 6 months control, and finally, one measurement 6 months before the angioplasty during the procedure on the 1st site. Multivariate statistical analysis showed that the only predictive factor of post-angioplasty loss in the general population was the immediate gain (F = 11.82; p < 0.005). On the other hand, no correlation was found between progression of the lesion before angioplasty and loss. The rapidly progressive nature of the lesion was defined with a threshold of 0.4 mm, corresponding to the variability of the quantitative angiographic system. Analysis of the procedure parameters showed a lower inflation pressure in the Gr with rapidly progressive lesions (6.58 +/- 21 atm vs 7.63 +/- 1.96 atm; p < 0.05). The immediate gain was significantly greater in the rapidly progressive lesion Gr (0.82 +/- 0.34 vs 0.67 +/- 0.29 mm; p = 0.05). The loss at the 6 months control was identical in the two Gr (0.31 +/- 0.50 vs 0.31 +/- 0.42 mm; p < 0.05). The loss/gain ratio was also comparable (0.37 +/- 0.76 vs 0.45 +/- 0.52; p > 0.05). These results show that rapidly progressive atherosclerosis does not increase the risk of post-angioplasty restenosis.