Sustained benefit of stenting chronic coronary occlusion: long-term clinical follow-up of the Stenting in Chronic Coronary Occlusion (SICCO) study.

OBJECTIVES: This study assessed the long-term clinical outcome of stenting chronic occlusions. BACKGROUND: In the Stenting in Chronic Coronary Occlusion (SICCO) study, patients were randomized to additional stent implantation (n = 58) or not (n = 59) after successful recanalization and dilation of a chronic coronary occlusion. Palmaz-Schatz stents were used with full anticoagulation. The previously published 6-month angiographic follow-up results showed reduction of the restenosis rate from 74% to 32%. METHODS: The primary end point was the occurrence of major adverse cardiac events (cardiac death, lesion-related acute myocardial infarction, repeat lesion-related revascularization or angiographic documentation of reocclusion). RESULTS: Late clinical follow-up was obtained in all patients at 33 +/- 6 months. Major adverse cardiac events occurred in 14 patients (24.1%) in the stent group compared with 35 patients (59.3%) in the percutaneous transluminal coronary angioplasty (PTCA) group (odds ratio 0.22, 95% confidence interval 0.10 to 0.49, p = 0.0002). Target vessel revascularization (including failed PTCA attempts) was performed in 24% of the stent group and in 53% of the PTCA group (p = 0.002). There were no events in the stent group after 8 months, whereas events continued to occur in the PTCA group. By multivariate analysis, allocation to the PTCA group, left anterior descending coronary artery lesion and lesion length were significantly related to the development of major adverse cardiac events. CONCLUSIONS: These data demonstrate the long-term safety and clinical benefit of stenting recanalized chronic occlusions. There is a continued risk of late clinical events related to nonstented lesions. Implantation of an intracoronary stent should therefore be considered after successful opening of a chronic coronary occlusion.

Stenting in small coronary arteries (SISCA) trial. A randomized comparison between balloon angioplasty and the heparin-coated beStent.

OBJECTIVES: The purpose of this study was to assess the clinical and angiographic benefits of elective stenting in coronary arteries with a reference diameter of 2.1 to 3.0 mm, as compared with traditional percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: The problems related to small-vessel stenting might be overcome using modern stents designed for small vessels, combined with effective antiplatelet therapy. METHODS: In five centers, 145 patients with stable or unstable angina were randomly assigned to elective stenting treatment with the heparin (Hepamed)-coated beStent or PTCA. Control angiography was performed after six months. The primary end point was the minimal lumen diameter (MLD) at follow-up. Secondary end points were the restenosis rate, event-free survival and angina status. RESULTS: At follow-up, there was a trend toward a larger MLD in the stent group (1.69 +/- 0.52 mm vs. 1.57 +/- 0.44 mm, p = 0.096). Event-free survival at follow-up was significantly higher in the stent group: 90.5% vs. 76.1% (p = 0.016). The restenosis rate was low in both groups (9.7% and 18.8% in the stent and PTCA groups, respectively; p = 0.15). Analyzed as treated, both the MLD and restenosis rate were significantly improved in patients who had stents as compared with PTCA. CONCLUSIONS: In small coronary arteries, both PTCA and elective stenting are associated with good clinical and angiographic outcomes after six months. Compared with PTCA, elective treatment with the heparin-coated beStent improves the clinical outcome; however, there was only a nonsignificant trend toward angiographic improvement.

Stenting in Chronic Coronary Occlusion (SICCO): a randomized, controlled trial of adding stent implantation after successful angioplasty.

OBJECTIVES: This study investigated whether stenting improves long-term results after recanalization of chronic coronary occlusions. BACKGROUND: Restenosis is common after percutaneous transluminal coronary angioplasty (PTCA) of chronic coronary occlusions. Stenting has been suggested as a means of improving results, but its use has not previously been investigated in a randomized trial. METHODS: We randomly assigned 119 patients with a satisfactory result after successful recanalization by PTCA of a chronic coronary occlusion to 1) a control (PTCA) group with no other intervention, or 2) a group in which PTCA was followed by implantation of Palmaz-Schatz stents with full anticoagulation. Coronary angiography was performed before randomization, after stenting and at 6-month follow-up. RESULTS: Inguinal bleeding was more frequent in the stent group. There were no deaths. One patient with stenting had a myocardial infarction. Subacute occlusion within 2 weeks occurred in four patients in the stent group and in three in the PTCA group. At follow-up, 57% of patients with stenting were free from angina compared with 24% of patients with PTCA only (p < 0.001). Angiographic follow-up data were available in 114 patients. Restenosis (> or = 50% diameter stenosis) developed in 32% of patients with stenting and in 74% of patients with PTCA only (p < 0.001); reocclusion occurred in 12% and 26%, respectively (p = 0.058). Minimal lumen diameter (mean +/- SD) at follow-up was 1.92 +/- 0.95 mm and 1.11 +/- 0.78 mm, respectively (p < 0.001). Target lesion revascularization within 300 days was less frequent in patients with stenting than in patients with PTCA only (22% vs. 42%, p = 0.025). CONCLUSIONS: Stent implantation improved long-term angiographic and clinical results after PTCA of chronic coronary occlusions and is thus recommended regardless of the primary PTCA result.

Reproducibility of cardiac stroke volume estimated by Doppler echocardiography.

Doppler echocardiography was used to measure cardiac stroke volume in 10 patients with coronary artery disease who were treated with cardioactive drugs. Stroke volume estimates were determined at the aortic orifice by multiplying area by systolic velocity integral measured both from the suprasternal and the apical approach. Recordings were done independently by 2 experienced observers on the same day and repeated once after 1 to 21 days. Analysis of variance showed that no systematic differences were introduced by the 2 observers and Doppler approaches or by measuring on different days. The coefficient of variation between any pair of measurements in each patient was 9%. This variability is probably a result of the method or spontaneous fluctuations of the stroke volume and not of the varying recording conditions. The ultrasonic method detects day-to-day changes of cardiac stroke volume larger than 20% with a probability greater than 0.95.

Reproducibility of echocardiographic estimates of the area of stenosed aortic valves using the continuity equation.

Interobserver variability in echocardiographic estimates of the area of stenosed aortic valves was assessed in 30 consecutive patients. Using the continuity equation, two independent observers calculated the area of stenosis from separate recordings of the diameter of the aortic orifice and the velocity time integral in the left ventricular outflow tract and in the stenotic jet. No significant difference between the observers was noted for any measurement. With respect to the area of stenosis, a high correlation between the observers was found (r = 0.92, P less than 0.001) and the regression line was close to the line of identity. The 95% limits of agreement were less than +/- 0.3 cm2. No discrepancy between the observers was found in the assessment of cases for aortic stenosis less than 0.8 cm2. Regression analyses showed good interobserver agreement also for the diameter of the orifice, the velocity time integrals, and the mean pressure gradient (r greater than 0.90, P less than 0.001). The greatest variability was noted for the diameter of the aortic orifice (95% limits of agreement +/- 1.4 cm2). We conclude that echocardiography enables reproducible estimates of the orificial area of stenosed aortic valves. Changes greater than 0.3 cm2 can be detected with a confidence probability of 95%. The greatest source of error is the measurement of the diameter of the outflow tract at the basal attachments of the aortic leaflets.

Predictors for restenosis after angioplasty of chronic coronary occlusions.

BACKGROUND: The Stenting In Chronic Coronary Occlusion (SICCO) study assessed the effects of additional intracoronary stenting (Palmaz-Schatz) after successful percutaneous transluminal coronary angioplasty (PTCA) of chronic coronary occlusions and showed a significant reduction of restenosis in stented patients. METHODS: Univariate and logistic regression analyses were used to assess clinical, angiographic and procedure related predictors for restenosis (>50% diameter stenosis at follow-up) and Major Adverse Clinical Events (MACE=cardiac death, lesion-related acute myocardial infarction, repeat lesion-related angioplasty, bypass surgery involving the treated segment or angiographic documentation of reocclusion in non-revascularized patients) in the 114 SICCO patients with an angiographic end-point and 300 days clinical follow-up. RESULTS: By 6 months the restenosis rate was 53%, and after 300 days MACE had occurred in 39%. Both the rates of restenosis and MACE was significantly reduced by stenting. The restenosis rate was improved by stenting also in patients with a 'stentlike' result after the initial PTCA. In the multivariate model the risk of restenosis was increased by a history of unstable angina, a long lesion and a non-tapering occlusion stump. LAD location was associated with a threefold increased risk of MACE. CONCLUSION: Stent implantation should always be considered in successfully opened chronic occlusions.

Effects of verapamil on left ventricular relaxation and filling dynamics in coronary artery disease: a study by pulsed Doppler echocardiography.

The effect of verapamil on left ventricular diastolic function in coronary artery disease was assessed by Doppler echocardiography of transmitral flow velocities in 20 patients. At baseline, isovolumic relaxation time was prolonged compared with that in 18 age-matched normal subjects (95 +/- 13 msec versus 74 +/- 12 msec, p less than 0.001), but decreased to 80 +/- 14 msec (p less than 0.001) after treatment. The ratio between early and atrial-induced transmitral velocities (E/A-ratio) at baseline was lower in patients than in normal subjects (1.1 +/- 0.2 versus 1.4 +/- 0.3, p = 0.01), as was the filling fraction of the first third of diastole (43% +/- 5% versus 50% +/- 4%, p less than 0.001). Verapamil treatment increased the E/A-ratio to 1.3 +/- 0.4 (p less than 0.001) and filling fraction to 45% +/- 4% (p = 0.055) because of increased early filling. No change in systolic performance or heart rate was observed. Thus, coronary artery disease was associated with retarded relaxation and impairment of early filling. However, verapamil treatment enhanced relaxation and induced a filling shift toward early diastole, which indicated improved diastolic performance. The changes probably reflected reduced myocardial ischemia.

Assessment of left ventricular relaxation by Doppler echocardiography. Comparison of isovolumic relaxation time and transmitral flow velocities with time constant of isovolumic relaxation.

Isovolumic relaxation time (IVRT) and events of early transmitral flow measured by Doppler echocardiography were validated against the time constant of left ventricular relaxation (tau) in open-chest dogs. During increased inotropy (by isoproterenol infusion) at constant preload, enhancement of relaxation was indicated by a decrease in tau from 48 +/- 12 (mean +/- SD) to 33 +/- 5 msec (p = 0.04) with a concomitant decrease in IVRT from 74 +/- 18 to 38 +/- 8 msec (p = 0.03). During decreased inotropy (by propranolol infusion) at constant preload, slowing of relaxation was indicated by an increase in tau from 40 +/- 8 to 51 +/- 13 msec (p = 0.02) with a concomitant increase in IVRT from 71 +/- 15 to 83 +/- 21 msec (p less than 0.05). A significant correlation between changes in tau and changes in IVRT was found (r = 0.66, p less than 0.001). In contrast, when left ventricular end-diastolic pressure was increased from 7 +/- 2 to 24 +/- 4 mm Hg at constant inotropy, tau increased from 47 +/- 14 to 64 +/- 25 msec (p = 0.03), whereas no change in IVRT was observed (76 +/- 19 and 71 +/- 19 msec, respectively). Aortic pressure was not significantly changed during any intervention, and heart rate was kept constant by pacing. Peak early transmitral velocity was unchanged by propranolol but increased during isoproterenol and saline infusion (p less than 0.001 and p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

[Atherectomy. A new catheterization method for coronary revascularization]. / Aterektomi. En ny katetermetode for koronar revaskularisering.

Intimal atheroma con be excised and removed by coronary atherectomy. We describe our experience from the use of this method in the first 42 patients. The procedure was successful in 40 patients, in 16 cases after adjunct percutaneous transluminal coronary angioplasty. Two patients required bypass surgery because of catheter-related injury to the coronary vessel. One of these suffered a myocardial infarction, the only infarction in the material. In-hospital complications were minor, and the average stay in hospital after the procedure was 1.6 days. Angiography in 20 patients after a median follow-up period of 116 days showed restenosis in 30%, all of whom were treated successfully with PTCA. Symptomatic improvement was reported by 74% of the patients after a median observation time of 16 months. One patient died, probably from infarction, three months after the initial treatment, one patient suffered a non-fatal infarction, and one patient underwent bypass surgery. We conclude that atherectomy is an effective and safe treatment of coronary heart disease in selected cases, mainly eccentric stenoses and ostial lesions.

[Intracoronary stents. Experience from the Feiring clinic]. / Intrakoronar stentbehandling. Erfaringer fra Feiringklinikken.

There are two major problems connected to percutaneous transluminal coronary angioplasty (PTCA): acute closure of the vessel during the procedure and a high rate of late restenosis. Deployment of intracoronary stents has emerged as a procedure that can counteract these difficulties. At the Feiring Clinic 158 patients were treated with intracoronary stents in 1992 and 1993. In 87% of the patients no in-hospital cardiac events occurred. The overall mortality rate was 1.8%. Thrombosis of the stent occurred in 5.7% of the patients and acute myocardial infarction in 5.1%. Emergency bypass operation was performed in 5.1%. The most important predictor for clinical success was a good angiographic appearance after deployment of stent. It is concluded that stent deployment has improved the immediate outcome of a complicated PTCA procedure, and it is likely that it also will reduce the rate of restenosis.

Age-dependency of left ventricular filling dynamics and relaxation as assessed by pulsed Doppler echocardiography.

Left ventricular diastolic function was assessed from transmitral flow velocity curves as measured by Doppler echocardiography in healthy individuals aged 21-69 years, each decade comprising 12 subjects. By ageing, progressive changes in the various filling parameters were observed. When comparing the youngest and oldest age groups, the ratio between peak velocities in early and late diastole decreased from 2.0 +/- 0.3 to 1.2 +/- 0.3 (P less than 0.001). The filling fraction of first third of diastole decreased from 54 +/- 5% to 45 +/- 4% (P less than 0.001). Isovolumic relaxation time increased from 61 +/- 11 ms to 77 +/- 12 ms (P less than 0.01). Correlation coefficients of velocity ratio, filling fraction and isovolumic relaxation time vs. age were r = -0.71 (P less than 0.001), r = -0.56 (P less than 0.001) and r = 0.44 (P less than 0.001), respectively. When isovolumic relaxation time and age were used together in multivariate regression analysis, only age was an independent predictor of velocity ratio and filling fraction. Stroke volume, peak velocity in left ventricular outflow tract, heart rate and systolic blood pressure were similar in all age groups. Thus, velocity ratio and filling fraction indicated a relative filling shift towards late diastole by ageing and were more sensitive than systolic parameters in reflecting age-related changes in cardiac function. The changes could be explained neither by delayed relaxation nor by change in systolic parameters. When using Doppler echocardiography for evaluation of left ventricular filling, age-matching of reference groups is necessary.

[Treatment with ticlodipine after intracoronary stent implantation]. / Behandling med tiklopidin etter intrakoronar stentimplantasjon.

Complications were registered prospectively in 100 patients who had had a successful intracoronary stent implantation as assessed by quantitative angiography. The reference diameter of the vessels was 3.29 +/- 0.52 mm. Instead of the traditional treatment with dextran, heparin, warfarin, acetylsalicylic acid (ASA) and dipyridamol, all patients received the platelet antagonist ticlopidine 250 mg twice daily for 28 days together with ASA 160 mg daily. In the first 50 patients low molecular weight heparin was injected for three days. There was no incidence of stent occlusion within one month after the stent implantation. Only one patient needed surgical repair because of groin haematoma, whereas three patients needed prolonged compression in the groin because of bleeding. Ticlopidine was withdrawn because of side effects in 11 patients. No serious haematological side effect was seen. In the patients who received low molecular weight heparin the stay in hospital was 5.3 +/- 1.0 days, whereas the remaining 50 patients stayed in the hospital for 2.8 +/- 1.9 days. Thus, compared with traditional anticoagulation therapy, treatment with ticlopidine and ASA after stent implantation prevented stent occlusion, groin complications were few, and the need for hospitalization was reduced.

Reproducibility of quantitative coronary analysis, Assessment of variability due to frame selection, different observers, and different cinefilmless laboratories.

Because of limited storage capacity for digital images, angiographic laboratories without cinefilm are dependent on locally performed quantitative coronary angiography (QCA) in clinical studies. In the present study the intra- and interobserver variability, as well as variability between different laboratories and variability due to frame selection was analyzed. A total of 20 coronary lesions were studied in two different laboratories 12 +/- 8 days apart. Images were analyzed on-line and after being transferred to a Cardiac Work Station (CWS). There was no significant difference between the measurement situations. For minimal luminal diameter (MLD) precision (SD of signed errors) ranged from 0.12 mm to 0.20 mm, for reference diameter (RD) from 0.15 mm to 0.28 mm, and for percent diameter stenosis (DS) from 4.2% to 5.8%. Overall relative precision was obtained by normalizing the QCA parameters, as well 11.9% for MLD, 7.0% for RD and 8.5% for DS (p < 0.001, Rd and DS compared to MLD). The overall variability in the interobserver and in the interlaboratory comparisons was 11.2% and 10.4%, respectively (n.s) (n.s.). Thus the variability of QCA performed in cinefilmless, digital laboratories is small, and within a range making it an useful tool for clinical practice and group comparisons in clinical studies. However, the error range of QCA measurements must be taken into consideration when judging results from individual patients.

Left ventricular filling at elevated diastolic pressures: relationship between transmitral Doppler flow velocities and atrial contribution.

The relationship between transmitral Doppler blood flow velocities and atrial contribution to left ventricular (LV) filling was investigated in seven open-chest dogs. At LV filling pressures greater than 15 to 20 mm Hg, LV volume approaches a maximum. Thus we hypothesized that when LV pressure before the onset of atrial systole exceeds this level, the atrial contribution would decrease and the ratio between peak early (E) and atrial-induced (A) mitral velocities would increase. Atrial contribution was measured as LV diameter increase during atrial contraction expressed as a percentage of the total LV diameter change during diastole (sonomicrometry). When left ventricular end-diastolic pressure (LVEDP) was progressively increased from 10 +/- 1 (mean +/- standard deviation) to 28 +/- 3 mm Hg by intravenous saline solution, the atrial contribution decreased from 34 +/- 14% to 8 +/- 10% (p less than 0.001). Concomitantly the A velocity decreased from 39 +/- 7 to 24 +/- 8 cm.sec-1 (p less than 0.01), and the E/A ratio increased from 1.8 +/- 0.3 to 3.6 +/- 1.5 (p less than 0.001). The E/A ratio and the atrial contribution were constant until LVEDP exceeded 17 to 20 mm Hg, at which level marked changes in both parameters were noted. Thus when LV filling pressure was increased, the E/A ratio increased, indicating a filling shift towards early diastole. The reduced atrial contribution during increased preload was explained by the curvilinear shape of the LV pressure-volume curve. At markedly elevated filling pressures, near-maximum LV diameter was achieved before atrial contraction; hence the atrial contribution decreased and the E/A ratio increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of beta-adrenergic blockade on left ventricular relaxation and filling dynamics in coronary artery disease: a pulsed Doppler echocardiographic study.

Left ventricular (LV) filling as assessed by Doppler transmitral flow velocity measurements was studied in 20 male patients with coronary artery disease (CAD) and in 18 normal individuals. Stroke volume, blood pressure and heart rate in the two groups were not significantly different. Compared to normals, the ratio between early and atrial-induced peak velocities was significantly lower in the patients (1.2 +/- 0.3 vs. 1.40 +/- 0.3, P = 0.01), as was the fraction of transmitral filling during the first 1/3 of diastole (45 +/- 7% vs. 50 +/- 4%, P less than 0.001). Isovolumic relaxation time (IV R) was 96 +/- 13 ms in patients vs. 74 +/- 12 ms in normals (P less than 0.001). The CAD patients were treated with atenolol for 13-24 days. The velocity ratio increased by 30% (P less than 0.001) due to a 12% increase in early (P = 0.004) and an 11% decrease in atrial-induced peak velocities (P = 0.01). Filling fraction and deceleration rate of early inflow both increased by 22% (P less than 0.001). IV R decreased by 8% (P = 0.01). After atenolol treatment, heart rate and blood pressure decreased by 23% and 10% (P less than 0.001), respectively, whereas stroke volume increased by 14% (P less than 0.001). Thus, CAD was associated with Doppler indices of retarded LV filling and myocardial relaxation. After atenolol treatment, significant increases in velocity ratio and filling fraction indicated a shift of filling from late towards early diastole, suggesting improved diastolic function. However, different factors related to beta-adrenergic blockade may have contributed to the observed changes.

[Should older patients be admitted for coronary evaluation and treatment? With special emphasis on a survey and catheter-based revascularization of patients over 70 years of age]. / Bør eldre henvises til koronar utredning og behandling? Saerlig omtale av utredning og kateterbasert revaskularisering av pasienter over 70 år.

A three year survey of patients undergoing diagnostic left heart catheterization and PTCA treatment is presented from Feiringklinikken. Data on patients over and under 70 years have been analysed separately. The fraction of patients over 70 years admitted for catheterization increased significantly from 18.8% to 23.4% during the survey period. Angiography was associated with a low mortality of 0.04% and incidence of cerebrovascular complications with 0.1%, with no increased risk in patients over 70 years. The proportion of patients treated with PTCA increased significantly during the survey from 25% to 39% for patients over 70 years and from 31% to 42% for patients under 70 years (p < 0.01). The initial success rate of PTCA was 89% and 92% for patients over and under 70 years respectively (not significant). The rate of serious complications was low in both age groups, 3.2% and 1.0% in patients over and under 70 years respectively (p < 0.01). Older patients can be examined invasively with low risk of complications. A substantial number of patients, also among the elderly, can be treated safely with PTCA with good initial results. Thus, elderly patients should be offered the benefit of invasive diagnosis and treatment for coronary heart disease.

Acute phase reactants and complement activation in patients with acute myocardial infarction.

The acute phase proteins, C-reactive protein (CRP), orosomucoid, alpha 1-antitrypsin and haptoglobin, the native complement components C3 and C4, activation products of C3, and the terminal SC5b-9 complement complex were quantified in samples obtained on admittance and on days 1, 2, 3 and 6 in 21 patients with non-complicated acute myocardial infarction (AMI) and in 22 controls. For all proteins peak and median concentrations were higher in the AMI group than in the controls, but the difference was significant only for CRP and orosomucoid. Median CRP concentration was 46 mg/l in the AMI group and 2.5 in the control group. The corresponding orosomucoid concentrations were 1.6 and 1.2 g/l. There was no correlation between the concentration of CRP in peripheral blood and the degree of complement activation. Furthermore, no correlation was observed between complement activation and the size of infarction. The present study cannot demonstrate that the increased concentrations of CRP and other acute phase reactants observed in patients with AMI, are associated with systemic fluid-phase complement activation. Furthermore, the complement activation previously shown locally in infarcted myocardium cannot be demonstrated systemically in non-complicated AMI.

Intravenous injection of Albunex microspheres causes thromboxane mediated pulmonary hypertension in pigs, but not in monkeys or rabbits.

Intravenous injection of the ultrasound contrast agent Albunex (manufactured by Nycomed AS, Oslo, Norway; 400 million air-filled albumin microspheres per ml, mean diameter 4 +/- 1 microns) caused a dose-dependent increase of mean pulmonary arterial pressure in nine pigs. The highest dose (0.014 +/- 0.002 ml kg-1) increased mean pulmonary arterial pressure from 17 +/- 1 mmHg to 42 +/- 3 mmHg and decreased mean systemic arterial pressure from 111 +/- 9 to 93 +/- 12 mmHg. The pressure responses began 22 +/- 1 s after particle injection, and reached maximum after 51 +/- 3 s. No changes in mean pulmonary arterial pressure or mean systemic arterial pressure were observed after Albunex injections during treatment with indomethacin (10 mg kg-1 + 5 mg kg-1 h-1 i.v., n = 6) or the thromboxane A2 receptor antagonist HN-11500 (10 mg kg-1 + 5 mg kg-1 h-1 i.v., n = 3). No Doppler enhancement could be detected in a carotid artery following injection of 0.12 ml kg-1 Albunex during indomethacin treatment. In five rabbits, Albunex caused Doppler enhancement in a carotid artery, and 0.48 ml kg-1 did not affect mean pulmonary arterial pressure or other haemodynamic parameters in five rabbits or in three cynomolgus monkeys. The pressure response in pigs may be explained by release of thromboxane A2 from the pulmonary intravascular macrophages during phagocytosis of the microspheres. This response to Albunex was totally absent in rabbits and monkeys.