Johan Van Lierde

Safety and efficacy of low dose simvastatin in cardiac transplant recipients treated with cyclosporine

Hyperlipidemia is common in heart transplant patients. Lipid-lowering therapy poses special problems, yet may be important because accelerated graft atherosclerosis is the major factor limiting long-term survival. Simvastatin 5 mg/day was started > 6 months after surgery in 26 consecutive cardiac transplant recipients with a total serum cholesterol level of > 250 mg/dl. The dose of simvastatin was increased in 5-mg increments until total serum cholesterol fell below 220 mg/dl or until side effects developed or up to a maximal dose of 20 mg/day. The final average daily dose was 10 mg. Changes in serum lipid levels after 6 months of therapy were compared with data from a matched and concurrent control group of heart transplant patients not taking simvastatin. Immunosuppression for both groups consisted of CsA, AZA, and corticosteroids. In the simvastatin-treated group, the serum level of total cholesterol decreased by 27% from 315pm53 to 230pm38 mg/dl (P<0.0001), low density lipoprotein cholesterol decreased by 40% from 205pm30 to 123pm32 mg/dl (P<0.0001), and triglycerides decreased by 21% from 177pm89 to 140pm49 mg/dl (P<0.01). There was no significant change in high density lipoprotein cholesterol level. Body weight and CsA blood levels remained stable. Steroid intake decreased during the study period to a similar extent in both the treated and the control groups. In the control group, no significant changes in serum lipid levels were observed. Two patients experienced a mild form of myotoxicity. In one other patient simvastatin treatment was stopped after an acute pancreatitis of uncertain etiology developed. Low dose simvastatin effectively lowers total serum cholesterol, low density lipoprotein cholesterol, and triglycerides in heart transplant patients. With due precautions, the safety profile of the drug in this patient population seems reasonable.

Immediate and follow-up results of the conservative coronary angioplasty strategy for unstable angina pectoris

To assess the results of a conservative coronary angioplasty strategy in unstable angina pectoris, the records of 1,421 consecutive patients without previous myocardial infarction undergoing a first percutaneous transluminal coronary angioplasty (PTCA) between 1986 and 1990 were reviewed. Of these patients, 631 had unstable and 790 had stable angina pectoris. Only after an intense effort to medically control symptoms, the unstable patients underwent PTCA at an average of 15.4 days (range 1 to 76) after hospital admission. Primary clinical success was achieved in 91.7% of patients with unstable and in 94.4% of those with stable angina pectoris (p = not significant). In-hospital mortality rates were 0.3 and 0.1%, respectively (p = not significant). Nonfatal in-hospital event rates for acute myocardial infarction, cerebrovascular accident and coronary bypass surgery were only slightly higher in patients with unstable angina pectoris; however, the difference from the stable group was significant when all events were combined (9 vs 5.9%; p less than 0.04). During 6-month follow-up, no significant difference in adverse events was found between the groups. The respective rates for the unstable and stable groups were 0.4 and 0.2% for death, 5.5 and 5.1% for major nonfatal events, and 17.7 and 20.1% for repeat PTCA. These results suggest that use of a conservative PTCA strategy in the treatment of patients with unstable angina pectoris results in favorable and similar immediate and 6-month outcomes compared with those in patients with stable angina pectoris.

Angiographic assessment of the infarct-related residual coronary stenosis after spontaneous or therapeutic thrombolysis

The severity of the infarct-related residual coronary stenosis after spontaneous or therapeutic thrombolysis was quantitatively assessed in 91 patients with an acute myocardial infarction who were allocated to treatment in the acute stage with either a thrombolytic agent (100 mg of recombinant tissue-type plasminogen activator given over 3 h, 49 patients) or a placebo (42 patients). Heparin and aspirin were given to both groups until angiography was performed. Digital subtracted images of the infarct-related coronary vessel were obtained 10 to 14 days after hospital admission and were subsequently analyzed with the use of a computer-assisted coronary stenosis measurement system. Neither treatment group differed significantly in age, gender or location of the culprit coronary lesion. Median values (90% range) in the thrombolysis and control groups were, respectively, 1.95 (0.9 to 5.3) mm versus 1.7 (0.9 to 3.4) mm for stenosis length; 1.4 (0.8 to 2.7) mm versus 1.4 (0.9 to 1.8) mm for minimal luminal diameter; 57% (36% to 75%) versus 58% (44% to 71%) for diameter obstruction; 82% (59% to 95%) versus 82% (68% to 92%) for geometric area obstruction; and 78% (58% to 91%) versus 79% (66% to 90%) for densitometric area obstruction. The difference between the two groups was not statistically significant for any of these measurements. Thus, in this study no significant differences in anatomy or severity of residual coronary stenosis could be demonstrated at 10 to 14 days after an acute myocardial infarction in patients with a recanalized infarct-related vessel, whether or not thrombolytic therapy was given on admission. These results indicate that with effective antithrombotic treatment, gradual endogenous fibrinolysis or more rapid lysis induced by the infusion of a thrombolytic agent results in a similar infarct-related coronary lesion at the time of hospital discharge.

Intra- and interobserver variability of a fast on-line quantitative coronary angiographic system.

To evaluate intra- and interobserver variability of an on-line quantitative coronary angiographic system, 2 independent observers measured 166 primary lesions excluding total occlusions before and after coronary angioplasty. Each observer repeated his measurement 3 times at 14 days interval. The average percent diameter stenosis results obtained by observer 1 and 2 were almost identical, before (62.2% ± 12.0% and 62.6% ±11.4%, NS) and after (27.1% ± 12.0% and 26.9% ± 11.3%, NS) angioplasty.Variability was expressed as 95 % limits of agreement (mean difference ± 2 x SD). The intra-observer variability of observer 1 ranged from − 6.6% to 6.6% before angioplasty and from − 9.6% to 9.6% after angioplasty. The corresponding limits of observer 2 were − 8.0% to 7.5% and − 8.3% to 8.5%, respectively. The interobserver variability ranged from −10.4% to 9.6% before versus −12.5% to 13.1% after angioplasty. This variability was not influenced by vessel size. The widening of the limits observed after angioplasty was largely due to an increased variability in the measurements of the absolute minimal luminal diameter but not of the reference segment. We conclude that the intra- and interobserver variability of measurements obtained with an on-line quantitative angiographic system used for guiding coronary interventions is acceptable and without systematic bias in any direction for a wide range of primary coronary stenoses. However, the variability increases when images are acquired immediately after angioplasty.

Use of an autoperfusion catheter in the treatment of acute refractory vessel closure after coronary balloon angioplasty: immediate and six month follow up results

Objective—To determine the usefulness of the Stack autopersion dilatation catheter in patients with acute recurrent vessel closure during coronary angioplasty. Design—Prospective data collection. Setting—University hospital. Patients—In 37 of 1003 consecutive patients undergoing angioplasty between November 1989 and December 1990 acute vessel closure developed that could not be redilated by a conventional balloon catheter. 13 (35%) of these 37 patients were sent immediately for emergency bypass surgery. Intervention—In the remaining 24 patients an attempt was made to reopen the vessel with a Stack catheter. Main outcome measure—Successful reopening of the vessel. All successfully treated patients were followed for at least six months to detect recurrent ischaemia. Results—In 16 patients (67%) the Stack procedure was successful. Of the eight patients in whom reopening of the occluded vessel was not achieved, seven were sent for bypass surgery and one was successfully treated by emergency stent implantation. The 16 patients successfully treated with the Stack autoperfusion system were followed up for a mean (SD) of 6·7 (2·6) (range 2 to 11) months. Ten patients remained symptom free but early clinical restenosis developed in four (25%). Overall, only three (19%) of 16 patients experienced recurrence of severe (class III-IV) symptoms and required further mechanical revascularisation. Conclusion—These data support the use of the Stack autoperfusion catheter system in selected patients with acute vessel closure not responsive to attempted redilatation with conventional balloon catheters. The short-term outcome seen in this series of patients who were successfully treated with this coronary autoperfusion system is encouraging.

Long-term prognosis of male patients with an isolated chronic occlusion of the left anterior descending coronary artery

The purpose of this study was to determine the long-term prognosis of patients with an isolated total occlusion of the left anterior descending artery (LAD). A total of 173 male patients with a chronic LAD occlusion and less than 50% narrowing of the other coronary arteries (group I) was compared with a group of 177 male patients with only insignificant coronary artery disease and a normal left ventricular function (group II). Baseline characteristics of both groups were comparable except for the inclusion of 54 patients (31.2%) with moderately or markedly reduced left ventricular systolic function in group I. During an 8-year follow-up period there was a greater number of patients with cardiac events in group I when compared with group II: cardiac death 11.2% versus 0.6% (p less than 0.0001), myocardial infarction 12.7% versus 3.4% (p = 0.001), myocardial revascularization procedures 11.6% versus 3.4% (p = 0.04). Stepwise discriminant analysis showed that a reduced ejection fraction and a family history of coronary artery disease were the best predictors for these adverse cardiac events.

Changes in human coronary flow reserve after administration of intracoronary diltiazem

Epicardial coronary artery diameter (ECAD), coronary blood flow velocity (CBFV), and coronary flow velocity reserve (CFVR) were analyzed at baseline and after a 500 μg i.e. bolus of diltiazem in nonstenotic coronary arteries of awake humans. Furthermore, patients (n = 25) were first randomized to pretreatment either with placebo (n = 12) or isosorbide dinitrate (0.5 μg/kg/min infusion) (n = 13). Diltiazem resulted in a significant increase in epicardial diameter (+ 10%; p = 0.001) and in coronary blood How (CBF) (+ 30%; p = 0.0001). Whereas basal CBFV only slightly increased (+7% NS), there was a significant fall in CFVR (− 11%; p = 0.001). The increase in coronary diameter and CBF after administration of i.e. diltiazem was comparable in placebo- and nitrate-pretreated patients. The decrease in CFVR, however, was restricted to the placebo-pretreated patients (−21%; p = 0.0004). Apparently, diltiazem attenuated the CFVR but only in the absence of nitrates. Thus, diltiazem i.e. appears to enhance myocardial oxygen supply without deleterious effects on the distal coronary perfusion pressure.