Per Albertsson

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.

Continued benefit of coronary stenting versus balloon angioplasty: five-year clinical follow-up of Benestent-I trial.

OBJECTIVES This study sought to establish whether the early favorable results in the Benestent-I randomized trial comparing elective Palmaz-Schatz stent implantation with balloon angioplasty in 516 patients with stable angina pectoris are maintained at 5 years. BACKGROUND The size of the required sample was based on a 40% reduction in clinical events in the stent group. Seven months and one-year follow-up in this trial showed a decreased incidence of restenosis and clinical events in patients randomized to stent implantation. METHODS Data at five years were collected by outpatient visit, via telephone and via the referring cardiologist. Three patients in the stent group and one in the percutaneous transluminal coronary angioplasty (PTCA) group were lost to follow-up at five years. Major clinical events, anginal status and use of cardiac medication were recorded according to the intention to treat principle. RESULTS No significant differences were found in anginal status and use of cardiac medication between the two groups. In the PTCA group, 27.3% of patients underwent target lesion revascularization (TLR) versus 17.2% of patients in the stent group (p = 0.008). No significant differences in mortality (5.9% vs. 3.1%), cerebrovascular accident (0.8% vs. 1.2%), myocardial infarction (9.4% vs. 6.3%) or coronary bypass surgery (11.7% vs. 9.8%) were found between the stent and PTCA groups, respectively. At five years, the event-free survival rate (59.8% vs. 65.6%; p = 0.20) between the stent and PTCA groups no longer achieved statistical significance. CONCLUSIONS The original 10% absolute difference in TLR in favor of the stent group has remained unchanged at five years, emphasizing the long-term stability of the stented target site.

Mortality and Morbidity in Diabetic and Nondiabetic Patients During a 2-Year Period After Coronary Artery Bypass Grafting

OBJECTIVE To describe mortality and morbidity during a 2-year period after coronary artery bypass grafting (CABG) among diabetic and nondiabetic patients. RESEARCH DESIGN AND METHODS All the patients in western Sweden in whom CABG was undertaken between June 1988 and June 1991 and in whom concomitant procedures were not performed were registered prospectively. The study was a prospective follow-up. RESULTS Diabetic patients (n = 268) differed from nondiabetic patients (n = 1,859) in that more women were included, and the patients more frequently had a previous history of myocardial infarction (MI), hypertension, congestive heart failure, intermittent claudication, and obesity. Diabetic patients more frequently required reoperation and had a higher incidence of peri- and postoperative neurological complications. Mortality during the 30 days after CABG was 6.7% in diabetic patients versus 3.0% in nondiabetic patients (P < 0.01). Mortality between day 30 and 2 years was 7.8 and 3.6%, respectively (P < 0.01). During 2 years of follow-up, a history of diabetes appeared to be a significant independent predictor of death. Whereas the development of MI after discharge from the hospital did not significantly differ between the two groups; 6.3% of diabetic patients developed stroke versus 2.5% in nondiabetic patients (P < 0.001). CONCLUSIONS Diabetic patients have a mortality rate during the 2-year period after CABG that is about twice that of nondiabetic patients during both the early and late phase after the operation.

Evidence for obesity paradox in patients with acute coronary syndromes: a report from the Swedish Coronary Angiography and Angioplasty Registry.

AIMS The obesity paradox refers to the epidemiological evidence that obesity compared with normal weight is associated with counter-intuitive improved health in a variety of disease conditions. The aim of this study was to investigate the relationship between body mass index (BMI) and mortality in patients with acute coronary syndromes (ACSs). METHODS AND RESULTS We extracted data from the Swedish Coronary Angiography and Angioplasty Registry and identified 64 436 patients who underwent coronary angiography due to ACSs. In 54 419 (84.4%) patients, a significant coronary stenosis was identified, whereas 10 017 (15.6%) patients had no significant stenosis. Patients were divided into nine different BMI categories. The patients with significant stenosis were further subdivided according to treatment received such as medical therapy, percutaneous coronary intervention (PCI), or coronary artery by-pass grafting. Mortality for the different subgroups during a maximum of 3 years was compared using Cox proportional hazards regression with the lean BMI category (21.0 to <23.5 kg/m(2)) as the reference group. Regardless of angiographic findings [significant or no significant coronary artery disease (CAD)] and treatment decision, the underweight group (BMI <18.5 kg/m(2)) had the greatest risk for mortality. Medical therapy and PCI-treated patients with modest overweight (BMI category 26.5-<28 kg/m(2)) had the lowest risk of mortality [hazard ratio (HR) 0.52; 95% CI 0.34-0.80 and HR 0.64; 95% CI 0.50-0.81, respectively]. When studying BMI as a continuous variable in patients with significant CAD, the adjusted risk for mortality decreased with increasing BMI up to ~35 kg/m(2) and then increased. In patients with significant CAD undergoing coronary artery by-pass grafting and in patients with no significant CAD, there was no difference in mortality risk in the overweight groups compared with the normal weight group. CONCLUSION In this large and unselected group of patients with ACSs, the relation between BMI and mortality was U-shaped, with the nadir among overweight or obese patients and underweight and normal-weight patients having the highest risk. These data strengthen the concept of the obesity paradox substantially.

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.

The anti-tumour effect of low-dose continuous chemotherapy may partly be mediated by thrombospondin

Background: Tumour growth is dependent on angiogenesis. Antiangiogenic chemotherapy, i.e. continuous or metronomic low-dose chemotherapy, is a method for administrating cytostatics at a low and well-tolerated concentration without prolonged breaks. The target is the genetically stable endothelial cells playing a pivotal role in angiogenesis within the tumour. Different mediators could mediate the antiangiogenic effect of metronomic chemotherapy. One of these mediators could be thrombospondin (TSP). TSP is a potent inhibitor of angiogenesis and might therefore be important in controlling tumour growth. This study was designed to evaluate the effects of low-dose continuous or moderate-dose bolus chemotherapy on tumour growth and on tumour expression of TSP. Materials and methods: Rats bearing a malignant prostate tumour (Dunning AT-1) not expressing TSP were treated systemically with cyclophosphamide, doxorubicin or paclitaxel and the combination of cyclophosphamide and doxorubicin. Tumour growth and body weight were measured during the treatment. CD36, one of TSP’s main receptors, was also analysed. The expression pattern of TSP-1, TSP-2 and CD36 was investigated using immunohistochemistry and Western blot analyses. Q-PCR was used to analyse TSP-1 mRNA expression. Results: Low-dose cyclophosphamide and paclitaxel re-induced the expression of TSP in the tumours. However, following a bolus dose of doxorubicin, tumours showed no expression of TSP. Both cyclophosphamide and doxorubicin treatments decreased the tumour weight by more than 60% compared with vehicle controls. When cyclophosphamide and doxorubicin were combined the tumour weight was reduced by 47%, while paclitaxel reduced the tumour weight by 18% compared to the vehicle controls. Conclusions: Systemic low-dose continuous treatment of a rat prostate cancer model with cyclophosphamide and paclitaxel induced the expression of TSP in tumour tissue and inhibited tumour growth. These findings support the hypothesis that the anti-tumour effect of low-dose metronomic chemotherapy, at least with certain chemotherapeutics, is partly mediated by induction of endogenous antiangiogenic factors.

Mortality in takotsubo syndrome is similar to mortality in myocardial infarction — A report from the SWEDEHEART1 registry

BACKGROUND Takotsubo syndrome is an acute cardiovascular condition that predominantly affects women. In this study, we compared patients with takotsubo syndrome and those with acute myocardial infarction with respect to patient characteristics, angiographic findings, and short- and long-term mortality. METHODS From the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA), we obtained and merged data on patients undergoing coronary angiography in Västra Götaland County in western Sweden between January 2005 and May 2013. Short- and long-term mortality in patients with takotsubo (n=302) and patients with ST-elevation myocardial infarction (STEMI, n=6595) and non-ST-elevation myocardial infarction (NSTEMI, n=8207) were compared by modeling unadjusted and propensity score-adjusted logistic and Cox proportional-hazards regression. RESULTS The proportion of the patients diagnosed with takotsubo increased from 0.16% in 2005 to 2.2% in 2012 (P<0.05); 14% of these patients also had significant coronary artery disease. Cardiogenic shock developed more frequently in patients with takotsubo than NSTEMI (adjusted OR 3.08, 95% CI 1.80-5.28, P<0.001). Thirty-day mortality was 4.1% and was comparable to STEMI and NSTEMI. The long-term risk of dying from takotsubo (median follow-up 25 months) was also comparable to NSTEMI (adjusted HR 1.01, 95% CI 0.70-1.46, P=0.955) STEMI (adjusted HR 0.83, 95% CI 0.57-1.20, P=0.328). CONCLUSIONS The proportion of acute coronary syndromes attributed to takotsubo syndrome in Western Sweden has increased over the last decade. The prognosis of takotsubo syndrome is poor, with similar early and late mortality as STEMI and NSTEMI.

Spinal cord stimulation in angina pectoris with normal coronary arteriograms

BackgroundPatients with angina pectoris with normal coronary arteriograms, also known as Syndrome X (typical exercise-induced angina pectoris, positive exercise testing, and normal coronary arteriograms), are often difficult to treat with conventional forms of medical therapy. Spinal cord stimulation has been used in recent years for the treatment of severe angina pectoris refractory to conventional medical and surgical therapy in coronary artery disease. The aim of this study was to investigate the effects of spinal cord stimulation on angina pectoris with normal coronary arteriograms. MethodsTwelve patients underwent five bicycle exercise tests, three tests without (control), and two tests with spinal cord stimulation treatment. ResultsThe exercise tolerance of the patients increased (108± 22 W versus 96±21W; P< 0.001), the magnitude of ST-segment depression at comparable work load decreased (1.0± 0.6mm versus 1.5± 0.9mm; P< 0.01), time to angina increased (5.4 ± 2.2 min versus 2.7 ± 1.9 min; P< 0.01), and time to the appearance of ST-segment depression increased (3.5± 1.9 min versus 2.4 ± 1.6 min; P< 0.01).The rate-pressure product at maximum work load during treatment increased, compared with the maximum work load during the control session (28 038 ± 6124mmHg x bpm versus 25 222 ± 4519mmHgx bpm; P< 0.05 ) and the comparable work load during treatment (28 038 ± th6124mmHg x bpm versus 24 795 ± 5022mmHg x bpm; P< 0.01). ConclusionsSpinal cord stimulation has beneficial effects in angina pectoris with normal coronary arteriograms in terms of relief of symptoms of angina pectoris and improvement of exercise tolerance. These effects may be associated with a reduction in myocardial ischemia.

Secreted and Membrane-Associated Matrix Metalloproteinases of IL-2-Activated NK Cells and Their Inhibitors

We have previously documented that rat IL-2-activated NK (A-NK) cells produce matrix metalloproteinase-2 (MMP-2) and MMP-9. In this study, we describe mouse A-NK cell-derived MMPs, including MT-MMPs, and also TIMPs. RT-PCR analysis from cDNA of mouse A-NK cells revealed mRNA for MMP-2, MMP-9, MMP-11, MMP-13, MT1-MMP, MT2-MMP, TIMP-1, and TIMP-2. MMP-2 and MMP-9 expression was confirmed by gelatin zymography. Moreover, we report for the first time that MT-MMPs are expressed by NK cells, i.e., large granular lymphocytes as determined by both RT-PCR and Western blots. TIMP-1 expression was detected as a 29-kDa protein in Western blots. It is intriguing that TIMP-2 protein from A-NK cells was also detected as a 29-kDa protein, which is clearly different from the previously reported molecular mass of 21 kDa in mouse and human cells. In addition, inhibition of MMPs by BB-94, a selective inhibitor of MMP, significantly inhibited the ability of mouse A-NK cells to migrate through Matrigel, a model basement membrane. Taken together, these findings suggest that A-NK cells may therefore use multiple MMPs in various cellular functions, including degradation of various extracellular matrix molecules as they extravasate from blood vessels and accumulate within cancer metastases following their adoptive transfer.

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.