Rune Wiseth

Randomized Study on Simple Versus Complex Stenting of Coronary Artery Bifurcation Lesions: The Nordic Bifurcation Study

Background— The optimal stenting strategy in coronary artery bifurcation lesions is unknown. In the present study, a strategy of stenting both the main vessel and the side branch (MV+SB) was compared with a strategy of stenting the main vessel only, with optional stenting of the side branch (MV), with sirolimus-eluting stents. Methods and Results— A total of 413 patients with a bifurcation lesion were randomized. The primary end point was a major adverse cardiac event: cardiac death, myocardial infarction, target-vessel revascularization, or stent thrombosis after 6 months. At 6 months, there were no significant differences in rates of major adverse cardiac events between the groups (MV+SB 3.4%, MV 2.9%; P=NS). In the MV+SB group, there were significantly longer procedure and fluoroscopy times, higher contrast volumes, and higher rates of procedure-related increases in biomarkers of myocardial injury. A total of 307 patients had a quantitative coronary assessment at the index procedure and after 8 months. The combined angiographic end point of diameter stenosis >50% of main vessel and occlusion of the side branch after 8 months was found in 5.3% in the MV group and 5.1% in the MV+SB group (P=NS). Conclusions— Independent of stenting strategy, excellent clinical and angiographic results were obtained with percutaneous treatment of de novo coronary artery bifurcation lesions with sirolimus-eluting stents. The simple stenting strategy used in the MV group was associated with reduced procedure and fluoroscopy times and lower rates of procedure-related biomarker elevation. Therefore, this strategy can be recommended as the routine bifurcation stenting technique.

Drug-Eluting or Bare-Metal Stents for Coronary Artery Disease

BACKGROUND Limited data are available on the long-term effects of contemporary drug-eluting stents versus contemporary bare-metal stents on rates of death, myocardial infarction, repeat revascularization, and stent thrombosis and on quality of life. METHODS We randomly assigned 9013 patients who had stable or unstable coronary artery disease to undergo percutaneous coronary intervention (PCI) with the implantation of either contemporary drug-eluting stents or bare-metal stents. In the group receiving drug-eluting stents, 96% of the patients received either everolimus- or zotarolimus-eluting stents. The primary outcome was a composite of death from any cause and nonfatal spontaneous myocardial infarction after a median of 5 years of follow-up. Secondary outcomes included repeat revascularization, stent thrombosis, and quality of life. RESULTS At 6 years, the rates of the primary outcome were 16.6% in the group receiving drug-eluting stents and 17.1% in the group receiving bare-metal stents (hazard ratio, 0.98; 95% confidence interval [CI], 0.88 to 1.09; P=0.66). There were no significant between-group differences in the components of the primary outcome. The 6-year rates of any repeat revascularization were 16.5% in the group receiving drug-eluting stents and 19.8% in the group receiving bare-metal stents (hazard ratio, 0.76; 95% CI, 0.69 to 0.85; P<0.001); the rates of definite stent thrombosis were 0.8% and 1.2%, respectively (P=0.0498). Quality-of-life measures did not differ significantly between the two groups. CONCLUSIONS In patients undergoing PCI, there were no significant differences between those receiving drug-eluting stents and those receiving bare-metal stents in the composite outcome of death from any cause and nonfatal spontaneous myocardial infarction. Rates of repeat revascularization were lower in the group receiving drug-eluting stents. (Funded by the Norwegian Research Council and others; NORSTENT ClinicalTrials.gov number, NCT00811772 .).

Randomized Comparison of Coronary Bifurcation Stenting With the Crush Versus the Culotte Technique Using Sirolimus Eluting Stents The Nordic Stent Technique Study

Background—In a number of coronary bifurcation lesions, both the main vessel and the side branch need stent coverage. Using sirolimus eluting stents, we compared 2 dedicated bifurcation stent techniques, the crush and the culotte techniques in a randomized trial with separate clinical and angiographic end-points. Methods and Results—A total of 424 patients with a bifurcation lesion were randomized to crush (n=209) and culotte (n=215) stenting. The primary end point was major adverse cardiac events; cardiac death, myocardial infarction, target vessel revascularization, or stent thrombosis after 6 months. At 6 months there were no significant differences in major adverse cardiac event rates between the groups; crush 4.3%, culotte 3.7% (P=0.87). Procedure and fluoroscopy times and contrast volumes were similar in the 2 groups. The rates of procedure-related increase in biomarkers of myocardial injury were 15.5% in crush versus 8.8% in culotte group (P=0.08). A total of 324 patients had a quantitative coronary assessment at the index procedure and after 8 months. The angiographic end-points of in-segment and in-stent restenosis of main vessel and/or side branch after 8 months were found in 12.1% versus 6.6% (P=0.10) and in 10.5% versus 4.5% (P=0.046) in the crush and culotte groups, respectively. Conclusions—Both the crush and the culotte bifurcation stenting techniques were associated with similar and excellent clinical and angiographic results. Angiographically, there was a trend toward less in-segment restenosis and significantly reduced in-stent restenosis following culotte stenting.

Automated analysis of myocardial deformation at dobutamine stress echocardiography: an angiographic validation.

OBJECTIVES We investigated the accuracy of automated analysis of myocardial deformation during dobutamine stress echocardiography (DSE). BACKGROUND The time required for segmental measurement of strain rate imaging (SRI) limits its feasibility for quantification of DSE. METHODS Myocardial deformation was assessed at DSE in 197 patients, 76 with and 61 without coronary artery disease (CAD) at angiography, and 60 at low risk of CAD. Automated deformation analysis was based on velocity gradient and segment length methods of measuring longitudinal motion within a region of interest tracked through the cardiac cycle. Results were compared with independent wall motion scoring (WMS). Patients were randomly divided; group A (n = 69) established optimal cutoffs for the parameters and group B (n = 68) tested their accuracy. RESULTS The feasibility of WMS exceeded that of both SRI methods at rest and at peak stress. In group A, the area under the receiver-operating characteristics curve of the peak systolic strain rate was 0.90 by both methods, and the optimal cutoffs for detection of CAD were -1.3 (velocity gradient) and -1.2 s(-1) (segment length). The areas under the receiver-operating characteristics curves for end-systolic strain were less (0.87) by both methods, with respective cutoffs of 9% and 8%. In group B, the velocity and segment length methods had respective sensitivities of 87% and 84% for SR, and 87% and 88% for end-systolic strain. Both significantly exceeded that of WMS in the same group (75%). CONCLUSIONS Automated analysis of myocardial deformation at DSE is feasible and accurate, and may increase the sensitivity of expert conventional reading.

Secular decline in mortality from coronary heart disease in adults with diabetes mellitus: cohort study

Objective To examine trends in fatal coronary heart disease in adults with and without diabetes. Design Cohort study. Setting Two surveys of the Nord-Trøndelag health study (HUNT), a population based study in Norway. Participants 74 914 men and women from the first survey (1984-6) and 64 829 from the second survey (1995-7). Main outcome measure Age specific mortality from coronary heart disease among adults with and without diabetes during two consecutive nine year follow-up periods. Results A total of 2623 men and 1583 women died from coronary heart disease. Mortality rates were substantially lower during the most recent follow-up period: among men aged 70-79 without diabetes, deaths per 1000 person years declined from 16.38 to 8.79 (reduction 48%, 95% confidence interval 39% to 55%) and among women aged 70-79 from 6.84 to 2.68 (62%, 52% to 70%). Among the same age group with diabetes, deaths per 1000 person years in men declined from 38.97 to 17.89 (54%, 32% to 69%) and in women from 28.15 to 11.83 (59%, 37% to 73%). The reduction was more noticeable in age groups younger than 70 at baseline, and less pronounced among people aged 80 or more. Mortality from coronary heart disease was more than twofold higher in people with than without diabetes, with a slightly stronger association in women. The difference in mortality by diabetes status remained almost unchanged from the first to the second survey. Conclusion The strong general reduction in mortality rates from coronary heart disease from the first to the second follow-up period also benefited people with diabetes, but the more than twofold higher mortality from coronary heart disease associated with diabetes persisted over time.

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.

Safety in simple versus complex stenting of coronary artery bifurcation lesions. The Nordic Bifurcation Study 14-month follow-up results

AIMS The risk of stent thrombosis has been reported to increase with percutaneous coronary intervention (PCI) complexity. The present study reports the pre-specified secondary endpoint of a 14-month stent thrombosis and major adverse cardiac events in patients stented with a simple versus a complex bifurcation technique using sirolimus eluting stents (SES). METHODS AND RESULTS A total of 413 patients with a coronary bifurcation lesion were randomised to a simple treatment strategy; stenting of main vessel and optional stenting of side branch (MV group), or to a complex stenting strategy; stenting of both main vessel and side branch (MV+SB group). Mortality data were available in all patients and 14-month clinical follow-up data in 395 (96%) of the patients. After 14 months, the rates of definite, probable and possible stent thrombosis (ARC criteria) were 1.0% vs. 0.5%, 1.0% vs. 0% and 0.5% vs. 0% (ns) in the MV and in the MV+SB groups, respectively. Rates of MACE were 9.5% in the MV group and 8.2% in the MV+SB group (ns). Total death was seen in 2.4% vs. 1.0% and non-PCI related myocardial infarction in 2.0% vs. 1.0% in the MV and the MV+SB groups, respectively. CONCLUSIONS After 14 months, two months after recommended cessation of dual antiplatelet therapy, the rates of stent thrombosis and major adverse cardiac events were low and independent of treatment complexity in patients treated with SES for coronary artery bifurcation lesions.

Effect of a single dose of the interleukin-6 receptor antagonist tocilizumab on inflammation and troponin T release in patients with non-ST-elevation myocardial infarction: a double-blind, randomized, placebo-controlled phase 2 trial

AIMS Interleukin-6 (IL-6) contributes to atherosclerotic plaque destabilization and is involved in myocardial injury during ischaemia-reperfusion. Interleukin-6 is therefore a potential therapeutic target in myocardial infarction (MI). We hypothesized that the IL-6 receptor antagonist tocilizumab would attenuate inflammation, and secondarily reduce troponin T (TnT) release in non-ST-elevation MI (NSTEMI). METHODS AND RESULTS In a two-centre, double-blind, placebo-controlled trial, 117 patients with NSTEMI were randomized at a median of 2 days after symptom onset to receive placebo (n = 59) or tocilizumab (n = 58), administered as a single dose prior to coronary angiography. High sensitivity (hs) C-reactive protein and hsTnT were measured at seven consecutive timepoints between Days 1 and 3. The area under the curve (AUC) for high-sensitivity C-reactive protein was the primary endpoint. The median AUC for high-sensitivity C-reactive protein during hospitalization was 2.1 times higher in the placebo than in the tocilizumab group (4.2 vs. 2.0 mg/L/h, P < 0.001). Also, the median AUC for hsTnT during hospitalization was 1.5 times higher in the placebo group compared with the tocilizumab group (234 vs. 159 ng/L/h, P = 0.007). The differences between the two treatment groups were observed mainly in (i) patients included ≤2 days from symptom onset and (ii) patients treated with percutaneous coronary intervention (PCI). No safety issues in the tocilizumab group were detected during 6 months of follow-up. CONCLUSION Tocilizumab attenuated the inflammatory response and primarily PCI-related TnT release in NSTEMI patients.

Exercise hemodynamics in small (≤21 mm) aortic valve prostheses assessed by Doppler echocardiography☆

Exercise Doppler echocardiography was used to assess hemodynamics in 25 patients with a < or = 21 mm aortic valve prosthesis (14 with a Medtronic-Hall 21 mm valve, three with a Medtronic-Hall 20 mm valve, three with a Sorin 21 mm valve, one with a Duromedics 21 mm valve, and four with a Carpentier-Edwards 21 mm valve). A symptom-limited upright bicycle exercise test was performed, and Doppler gradients were recorded during exercise. Gradients increased with exercise from 30 +/- 8/16 +/- 4 mm Hg (peak/mean) at rest to 46 +/- 12/24 +/- 7 mm Hg during exercise; both p < 0.001. Mean exercise gradient exceeded 30 mm Hg in five patients, and the highest mean gradient recorded was 37 mm Hg. Within the group of mechanical valves, gradients at exercise were similar for different types of valves. A linear relationship was found between gradients at rest and during exercise (peak r = 0.75, mean r = 0.77; both p < 0.001). Additional findings were midventricular velocities exceeding 1.5 m/sec in late systole in 10 patients (40%) and intraventricular flow (> or = 0.2 m/sec) toward the apex during isovolumic relaxation in 11 patients (44%). The patients with these velocity patterns had significantly smaller left ventricular cavities (end-diastolic diameter 39.8 +/- 4.8 vs 46.5 +/- 4.2 mm, p < 0.01; end-systolic diameter 24.2 +/- 3.0 vs 28.5 +/- 4.5 mm, p = 0.013).(ABSTRACT TRUNCATED AT 250 WORDS)

The Additive Contribution from Inflammatory Genetic Markers on the Severity of Cardiovascular Disease

Inflammation plays a key role in the development of atherosclerosis. Genetic differences in molecules related to inflammation have therefore been linked to the susceptibility for and severity of atherosclerosis. We hypothesized that the additive contribution from different genes of importance for inflammation would enhance the severity of cardiovascular disease. Blood samples were collected from 230 adults admitted for elective coronary angiography. A total of 130 patients had significant (>50%) stenosis in at least one main coronary artery branch and 100 had not. Six polymorphisms in five different genes were analysed: myeloperoxidase (MPO) −129G/A and −463G/A, toll‐like receptor 4 (TLR4) Asp299Gly, interleukin‐6 (IL6) −174G/C, surfactant protein D (SFTPD) Met11Thr and regulated upon normal T‐cell expressed and secreted (CCL5) −403G/A. The IL6 polymorphism was significantly associated (P = 0.017) to angiographic significant coronary artery disease, and this relation remained after adjustment for age, gender, smoking and hypercholesterolaemia (P = 0.007). The TLR4 (P = 0.050) and SFTPD (P = 0.058) polymorphisms were also associated with the presence of coronary stenosis in univariate but not in multivariate analyses. For MPO and CCL5 no associations were found. There was a significant linear association between the number of high‐risk gene variants (IL6−174CC, SFTPD 11CC and TLR4 299AA) and the proportion of patients with coronary artery disease (P < 0.0005). Inherited factors related to inflammation may increase susceptibility for severe coronary artery disease. Furthermore, the additive contribution from different inflammatory genetic markers strongly enhances the individual severity of cardiovascular disease.