Jean M. Lablanche

Frequency of provoked coronary arterial spasm in 1089 consecutive patients undergoing coronary arteriography.

We established the incidence of coronary artery spasm provoked by 0.4 mg of methergine in 1089 consecutive patients undergoing coronary angiography. The test was performed after routine coronary arteriography. Subjects included patients with angina, both typical and atypical, patients who had recently had myocardial infarction and patients with either valvular disease or congestive cardiomyopathy. Patients with spontaneous spasm, left main narrowing or severe three-vessel disease were excluded. One hundred thirty-four patients experienced focal spasm. Focal spasm was uncommon in patients with atypical precordial pain (1.2%), angina of effort (4.3%), valvular disease (1.95%) or cardiomyopathy (0%). It occurred most often in patients with angina at rest and less often in patients with angina both at rest and induced by exercise. Spasm was provoked in 20% of patients with recent transmural infarction, but in only 6.2% of patients studied later after infarction. Spasm was superimposed on fixed atherosclerotic lesions in 60% of the patients. No serious complications were encountered. Although the patients who underwent provocation tests in this study are not representative of all patients with coronary artery disease, spasm occurred in 20% of patients who experienced a coronary event and in 15% of patients who complained of chest pain.

Long-term oral administration of L-arginine reduces intimal thickening and enhances neoendothelium-dependent acetylcholine-induced relaxation after arterial injury

BackgroundNitric oxide (NO), in addition to its potent vasorelaxant properties, may participate in growth regulation of cultured smooth muscle cells. It was recently demonstrated that in vivo endothelial injury induces the production of NO from L-arginine in the arterial wall. Methods and ResultsWe studied the effects of long-term administration of L-arginine, the precursor of NO, on neointimal thickening and on neoendothelium-dependent vasorelaxation 4 weeks after balloon denudation of normocholesterolemic rabbit iliac arteries. Rabbits were fed with either a standard diet or a diet supplemented with L-arginine (2.25%) in their drinking water 3 days before and during 4 weeks after balloon denudation. The effectiveness of L-arginine supplementation was confirmed by measurement of plasma arginine levels. L-Arginine had no effect on hemodynamic parameters. All animals were killed 4 weeks after balloon denudation, and a digital histomorphometric analysis of three serial nonconsecutive histological cross sections per iliac artery was performed. Intimal thickening was reduced (P<.05) from 0.43±0.08 (SE) mm2 in controls (n=8) to 0.24±0.02 mm2 in treated animals (n=8). Ten animals (n=5 in each group) were used for in vitro vasoreactivity assessment 4 weeks after balloon denudation. Neoendotheliumdependent acetylcholine-induced relaxation (10−8 mol/L to 3.10−5 mol/L) in treated animals (Emax=−24.1±5.5%) was significantly greater than in controls (Emax=−8.9±2.2%). Endothelium- independent relaxation did not differ between groups (Emax= −58.1±6.5% in L-argimine-supplemented animals versus −52.9±6.8% in controls). ConclusionsOur results demonstrate that L-arginine, a precursor of NO, reduces neointimal thickening after balloon denudation and improves neoendothelial-dependent acetylcholine- induced relaxation.

Percutaneous coronary rotational angioplasty in humans: Preliminary report

Percutaneous coronary rotational angioplasty was attempted in 12 patients. The procedure was performed with a flexible rotating shaft with an abrasive tip, varying in diameter from 1.25 to 3.5 mm, tracking along a central guide wire. Among the 12 patients (mean age 58 years), 4 had a stenosis in the left anterior descending coronary artery and 8 a stenosis in the right coronary artery. After the guide wire crossed the stenosis, the abrasive tip was slowly advanced and several passes across the stenosis were made. The residual stenosis was measured with computerized automatic quantitative coronary angiography. Success was defined as a reduction of percent stenosis by greater than 20%. If residual stenosis remained significant (greater than 50%), the procedure was completed by balloon dilation. The device could not be inserted in 2 of the 12 patients. Five of the 10 patients underwent rotational angioplasty alone, and 5 had the procedure completed by balloon dilation. The stenosis was significantly enlarged from 0.56 +/- 0.31 mm to 1.26 +/- 0.28 mm. The outline of the vessel appeared smooth and regular. There were no complications related to the procedure and all patients were free of symptoms when discharged 2 to 3 days after the procedure. Thus, coronary rotational angioplasty is a simple and safe procedure allowing marked dilation of the narrowed segment. However, long-term follow-up is required for further evaluation.

Coronary Sinus Blood Flow at Rest and During Isometric Exercise In Patients With Aortic Valve Disease Mechanism of Angina Pectoris in Presence of Normal Coronary Arteries

In 46 patients with aortic valve disease, coronary sinus blood flow was measured using a continuous thermodilution method both at rest and during isometric handgrip exercise. All patients had normal coronary angiograms. The patients were separated into three groups: Group I, 12 patients with aortic stenosis (systolic gradient 72 +/- 12 mm Hg); Group II, 15 patients with both aortic stenosis and regurgitation; Group III, 19 patients with aortic regurgitation. At rest, the coronary sinus blood flow was two to three times normal. However, when corrected for left ventricular mass (ml/100 g), flow was within normal limits. The ratio diastolic pressure-time index/systolic pressure-time index (DPTI/SPTI) was decreased in all three groups at rest. During isometric exercise, coronary sinus blood flow increased significantly: by 60 percent in Group I, by 88 percent in Group II and by 118 percent in Group III. There was a significant reduction of the DPTI/SPTI ratio. Of the 18 patients with angina on effort during the test, 7 were in Group I, 6 in Group II and 5 in Group III. There were no differences in the coronary sinus blood flow between the patients with angina and those who were pain-free, either at rest or during exercise. Angina pectoris does not appear to be caused by a failure of coronary blood flow to increase. There was no discrepancy between myocardial demand, as measured by the pressure-time index and coronary blood flow. However, the DPTI/SPTI ratio was significantly lower during exercise in the patients with angina than in those who were pain-free. Underperfusion of the subendocardial muscle seems to be a causative factor in the patients with angina.

Detrimental effect of propranolol in patients with coronary arterial spasm countered by combination with diltiazem

This study determines, with quantitative variables, if propranolol is detrimental in patients with documented coronary arterial spasm and if this drug can be used in combination with calcium antagonists. Eleven patients with documented coronary spasm were entered prospectively in a study with 4 phases of 2 days each: (1) control, (2) diltiazem or propranolol (mean 225 +/- 75 mg/day), (3) propranolol or diltiazem (360 mg/day), (4) propranolol and diltiazem. The effects of the drugs were assessed by the detection of ischemic electrocardiographic episodes (24-hour electrocardiographic monitoring) and provocative tests with ergonovine. During the period of treatment with propranolol, the number and the duration of attacks increased and provocative tests had positive results in all patients. Diltiazem completely abolished spontaneous episodes, but 6 of 11 patients remained sensitive to the administration of ergonovine. The association of the 2 drugs led to a disappearance of ischemic episodes. In conclusion, propranolol is ineffective in patients with coronary artery spasm. It can be used in combination with diltiazem, but without any advantage over diltiazem alone.

Surgical treatment of variant angina: use of plexectomy with aortocoronary bypass.

Aortocoronary bypass surgery, widely accepted in the treatment of patients with coronary artery disease, is controversial in the management of variant angina. Persistence of attacks, occlusion of the graft or postoperative infarction have been described and could be explained by a persistent spasm frequently observed in variant angina that might occlude the distal part of the grafted vessel.It has been suggested that plexectomy might be added to the aortocoronary graft procedure in order to prevent the spasm. Our study includes 35 patients with variant angina who had surgery. They were divided into two groups. Group 1 (n = 13) had aortocoronary bypass alone; the patients in group 2 had plexectomy in addition to the myocardial revascularization. The average follow-up period was 37 months in group 1 and 20 months in group 2. The results were assessed by clinical study, stress testing, control of patency of the grafts and provocative test with an ergot alkaloid (methergine).Despite the difficulties of evaluating the effects of the various treatments in these patients with a wide spontaneous variability of symptoms, these data suggest that a complete plexectomy associated with aortocoronary bypass gives better results (86%) than bypass alone (61%) in variant angina. The recurrence rate of attacks was lower (5%) when plexectomy was associated with bypass than with bypass alone (18%).

Relation to restenosis after percutaneous transluminal coronary angioplasty to vasomotion of the dilated coronary arterial segment

Among 868 patients with successful percutaneous transluminal coronary angioplasty (PTCA), 437 were restudied angiographically and had a provocative test with ergonovine during coronary angiography performed before and 6 months after the procedure. The relation between provoked coronary artery spasm and restenosis was studied and 4 groups of patients were analyzed. Those in group 1 (n = 63) had spasm before and after PTCA and their rate of restenosis was high (55%), especially when spasm after PTCA was observed on the dilated coronary segment (restenosis rate 58%). Patients in group 2 (n = 78) had spasm before PTCA but without abnormal vasoconstriction at 6 months and their incidence of restenosis was 19%. Sixty-one patients in group 3 had no spasm before PTCA but developed spasm at restudy. The rate of restenosis was high (38%) in this group, especially when the spasm after PTCA was located on the dilated segment (43%). In group 4 (n = 235), patients had no spasm before or after PTCA and the restenosis rate was 20%. Thus, the presence of coronary artery spasm on the dilated coronary segment, 6 months after a successful PTCA, is frequently accompanied (43% in group 3 and 58% in group 1) by restenosis.

Left ventricular systolic and diastolic function during acute coronary artery balloon occlusion in humans

Left ventricular function during percutaneous transluminal coronary angioplasty was studied in 16 patients undergoing the procedure. All measurements were performed before and during the first episode of balloon coronary occlusion. In 16 patients (Group A), data were recorded before and 30 or 50 s after balloon inflation, and in 8 of these patients (Group B) data were also recorded 15 min after the complete procedure. Left ventriculograms indicated a marked dyskinesia of the anterior and apical wall in all patients. After balloon inflation, there was a marked depression in stroke index and ejection fraction and an increase in left ventricular end-diastolic pressure and the time constants of relaxation in all patients. Simultaneous recording of left ventricular pressure (Millar micromanometer) during cineangiography permitted the assessment of myocardial and chamber stiffness. Although there was a strong tendency for both myocardial and chamber stiffness to increase after 30 to 50 s of occlusion, these increases were statistically insignificant. In Group B, a third set of angiographic and pressure measurements obtained 15 min after completion of the coronary angioplasty procedure indicated no residual left ventricular dysfunction, and in this respect, the results are of added clinical importance.

Comparative results of percutaneous transluminal coronary angioplasty in patients with dynamic versus fixed coronary stenosis

This study compares the results of percutaneous transluminal coronary angioplasty in a group of 132 patients (group A) with fixed atherosclerotic narrowing (no spontaneous or ergonovine-provoked spasm) and in a group of 97 patients (group B) with dynamic coronary stenosis (spasm superimposed on the stenosis). All these patients underwent complete follow-up angiography. The rate of restenosis (defined as a loss of 50% of the initial gain) was significantly higher in patients in group B (dynamic coronary stenosis) than in group A (fixed narrowing) (35 versus 22%, p less than 0.05). Despite treatment with a calcium antagonist, coronary artery spasm persisted in 44% of the patients in group B and was detected for the first time in 15% of the patients in group A. Thus, in patients with dynamic coronary stenosis, the results of coronary angioplasty were less satisfactory than in patients with fixed narrowing, and in both groups coronary artery spasm was frequently (64%) superimposed on the restenosis.

Effect of mitral valve surgery on exercise capacity, ventricular ejection fraction and neurohormonal activation in patients with severe mitral regurgitation

OBJECTIVES The purpose of this study was to prospectively investigate the effects of surgical correction of mitral regurgitation (MR) on exercise performance, cardiac function and neurohormonal activation. BACKGROUND Little is known about the effect of surgical correction of MR on functional status or on neurohormonal activation. METHODS Cardiopulmonary exercise test, radionuclide angiography and blood samples for assessment of neurohormonal status were obtained in 40 patients with nonischemic MR before and within one year (216+/-80 days) after surgery. Twenty-four patients underwent mitral valve repair (MVr), and 16 underwent valve replacement (VR) with anterior chordal transection. RESULTS Despite an improvement in New York Heart Association functional class, exercise performance did not change (peak oxygen consumption: 19.3+/-6.1 to 18.5+/-5.6 ml/kg/min, percentage of maximal predicted oxygen consumption: 79.5+/-18.2% to 76.8+/-16.9%). After surgery, left ventricular (LV) ejection fraction (EF) decreased (64.2+/-10.3% to 59.9+/-11.4%, p = 0.003) while right ventricular (RV) EF increased (41.4+/-9.6% to 44.7+/-9.5%, p = 0.03). Left ventricular EF did not change after MVr (64.3+/-11.5% to 61.5+/-12.2%), but RVEF improved (40.4+/-9.2% to 46.0+/-10.0%, p = 0.02). In contrast, VR was associated with an impairment of LV function in the apicolateral area and a decrease in LVEF (64.1+/-8.5% to 57.4+/-10.0%, p = 0.01), whereas RVEF did not change (42.9+/-10.3% to 42.8+/-8.6%). Moreover, there was only a slight decrease in neurohormonal activation after surgery. CONCLUSIONS Despite an improvement in symptomatic status, exercise performance was not improved seven months after either MVr or VR for MR, and neurohormonal activation persisted. Compared with MVr, VR resulted in a significant impairment of cardiac function in this study.