Polypharmacy and excessive polypharmacy in octogenarians and older acutely hospitalized patients.

AIM: The aim of this study was to assess the occurrence of polypharmacy and excessive polypharmacy in very old hospitalized patients based on their comorbidities. METHODS: The documentation of patients aged 80 years or older admitted to our department in the year 2010 was analyzed. Based on the Charlson index of comorbidity, a multiple logistic regression model with stepwise backward elimination was performed. Patients were stratified by gender and four age-groups, and factors of a change in the number of medications during the hospital stay were assessed. RESULTS: Chronic pulmonary disease [odds ratio (OR): 2.40], diabetes mellitus with (OR: 4.65) or without (OR: 1.65) microvascular complications, congestive heart failure (OR: 2.37), connective tissue disease (OR: 3.02), and peripheral vascular disease (OR: 2.30) were statistically significantly associated with polypharmacy, while some of these diseases were also associated with excessive polypharmacy. The number of medications showed a gradual decrease with age, which was concordant with a decrease in total Charlson index score. "Admission for myocardial infarction" was associated with an increase in pharmaceuticals during hospital stay, whereas a known diagnosis of dementia or metastatic malignant disease was protective against a further increase in medications. CONCLUSIONS: Several medical conditions seem to predispose to polypharmacy in very old patients. To attain old age seems to be associated with few comorbidities, which reduces the need for a high number of pharmaceuticals. Physicians should pay attention to the identified predictors in very old patients, as polypharmacy may lead to adverse events and unnecessary hospitalization.

Comparison of short- and long-term results of drug-eluting vs. bare metal stenting in the porcine internal carotid artery.

PURPOSE: To evaluate the development of neointimal hyperplasia after implantation of drug-eluting stents (paclitaxel) compared to bare metal stents in porcine internal carotid arteries (ICAs). METHODS: While drug-eluting stents have effectively reduced neointimal proliferation in porcine external carotid arteries, the porcine internal carotid artery (ICA) is more sensitive to shear stress and altered flow conditions. Thus, a study was conducted to evaluate bare vs. drug-eluting stents in porcine ICAs. Under general anesthesia, 18 domestic pigs were implanted with paclitaxel-eluting (n = 18) and bare (n = 18) stents in the left and right ICAs, respectively. After 1 and 3 months, control carotid angiography was performed, followed by histopathological and histomorphometric analyses of the stented ICA. RESULTS: Histopathological results (fibrin deposition, necrosis, inflammation) were similar in the groups at 1 and 3 months. Moreover, the injury score and rate of endothelialization did not differ between the groups. Histomorphometric analysis after 1 month revealed significantly (p<0.05) less neointimal hyperplasia after implantation of paclitaxel-eluting stents. The antiproliferative effect of paclitaxel-eluting stents were maintained during the 3-month follow-up: the neointimal area was 0.7 ± 0.5 vs. 1.2 ± 0.6 mm(2) (p<0.01), the area stenosis was 23.5% ± 13.9% vs. 37.8% ± 14.4% (p<0.01), the maximal neointimal thickness was 0.2 ± 0.1 vs. 0.2 ± 0.9 mm (p<0.05) in paclitaxel-eluting vs. bare stents, respectively. Implantation of paclitaxel-eluting and bare stents did not lead to edge restenosis or vessel remodeling in porcine ICAs at 1 or 3 months. CONCLUSION: Compared to bare metal stents, drug-eluting stents implanted in the porcine ICA produced significantly less neointimal hyperplasia.

The effects of strength and endurance training in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) suffer from muscle loss, causing reduced muscle strength and endurance. The current study aimed to: (1) evaluate the effects of combined strength and endurance training (CT) on disease activity and functional ability in patients with RA and (2) investigate the benefits of a 6-month supervised CT program on muscle strength, cardio-respiratory fitness, and body composition of RA patients. Forty patients with RA, aged 41-73 years, were recruited for the current study. Twenty of these patients (19 females, one male) were randomly assigned to a 6-month supervised CT program; 20 patients (17 females, three males) served as controls. Within the CT program, strength training consisted of sets of weight bearing exercises for all major muscle groups. In addition to strength training, systematic endurance training was performed on a cycle ergometer two times per week. For RA patients involved in CT, disease activity (p = 0.06) and pain (p = 0.05) were reduced after the 6-month training period while general health (p = 0.04) and functional ability (p = 0.06) improved. Cardio-respiratory endurance was found to have improved significantly (by 10%) after 6 months of CT (p < 0.001). The overall strength of patients undertaking CT increased by an average of 14%. Lean body mass increased, and the percentage of body fat was found to decrease significantly (p < 0.05). A combination of strength and endurance training resulted in considerable improvements in RA patients' muscle strength and cardio-respiratory endurance, accompanied by positive changes in body composition and functional ability. Long-term training appears to be effective in reducing disease activity and associated pain and was found to have no deleterious effects.

[Rehabilitation in ankylosing spondylitis]. / Rehabilitation bei Morbus Bechterew.

Modern treatment of patients with ankylosing spondylitis consists of therapies according to the ASAS criteria. Rehabilitation is a necessary process for enabling persons with disabilities caused by inflammatory destructions. The goal is to reach optimal physical, sensory, psychiatric and social health to reach higher levels of independence. It includes a wide range of measures and activities for changing the behaviour and increases activity, participation, strength, stability and coordination.

Observational study of switching anti-TNF agents in ankylosing spondylitis and psoriatic arthritis versus rheumatoid arthritis.

Anti-TNF agents like infliximab, etanercept and adalimumab are efficacious in the treatment of ankylosing spondylitis (AS), psoriatic arthritis (PsA) and rheumatoid arthritis (RA). Lack of efficacy, side effects and loss of efficacy over time may be reasons for switching to a second anti-TNF agent and sometimes switching to a third anti-TNF agent may be useful. Effects of switching may be different in patients with AS, PsA and RA. We analysed data of 301 patients with rheumatic diseases treated with anti-TNF agents. Forty-six patients had AS, 63 PsA and 192 RA. Totally 38% of these patients received more than one anti-TNF agent. Switching to a second anti-TNF agent was necessary in 115 (38%) of our patients, in detail in 11 of our AS patients, in 21 of PsA patients and in 83 of RA patients. Patient with PsA showed the best response rate to the second anti-TNF agent. Finally, 46 patients, 5 with SPA, 3 with PsA and 38 with RA received a third anti-TNF agent. We conclude that anti-TNF switching in AS and PsA is less frequent than in RA patients. Survival of anti-TNF agents in AS (p = 0.025) and also in PsA (n.s., p = 0.215) seems to be better than in RA. Switching anti-TNF agents for loss of efficacy over time may have the best effect in patients with AS, PsA and predominantly in RA. Our data suggest that switching for lack of efficacy in RA patients cannot be recommended, but may be an alternative in patients with AS and PsA. Switching to a second anti-TNF agent for side effects may be reasonable, switching to a third anti-TNF agent again for side effects cannot be recommended.

Comparison of different biologic agents in patients with rheumatoid arthritis after failure of the first biologic therapy.

Switching between different biologic agents for the treatment of rheumatoid arthritis has become a common practice even within similar substance groups. This longitudinal observational study was performed to follow the therapeutic management of patients with rheumatoid arthritis who were switched from one biologic therapy to another. We found no differences between the different biologic agents in regard to drug survival respectively efficacy, neither in the first nor in the second course of therapy. The reason to switch (side effect, lack of efficacy or loss of efficacy) did not influence the following treatment, although a lack of efficacy showed the shortest drug survival in the subsequent therapy. In conclusion, while switching between different biologic substances in rheumatoid arthritis is feasible and reasonable, the choice of substance has to be made on an individual basis.

Effects of progressive strength training on muscle mass in type 2 diabetes mellitus patients determined by computed tomography.

OBJECTIVE: To examine the effect of a 4-month progressive strength training program on muscle and fat mass assessed by computed tomography (CT) in type 2 diabetes mellitus (T2DM) patients, and to assess the relationships of changes in muscle cross-section area (CSA) with glycaemic control. METHODS: Twenty adults (mean age +/- SE: 56.4 +/- 0.9 a) with T2DM participated in a supervised strength training program for 4 months 3 days/week. Muscle and fat areas of the quadriceps muscle were estimated by CT volumetry before and immediately after the training. Glycaemic (HbA1c) and anthropometric (BMI, skinfolds) measurements were assessed at 0 and 4 months, respectively. RESULTS: After strength training, muscle strength increased significantly in all measured muscle groups. Quadriceps size (CSA of the muscle) was increased by 2.4% (from 7.99 +/- 0.3 cm(3) to 8.18 +/- 0.3 cm(3), p = 0.003) for the right extremity, 3.9% (from 8.1 +/- 0.4 cm(3) to 8.41 +/- 0.5 cm(3), p = 0.04) for the left side. Fat tissue CSA reduced from 0.66 +/- 0.1 cm(3) to 0.56 +/- 0.12 cm(3) for the right leg (15.3% reduction) and from 0.58 +/- 0.12 cm(3) to 0.37 +/- 0.13 cm(3) for the left leg (35.8% reduction), resulting in a mean fat CSA reduction of 24.8%. Fat mass assessed by skin folds was significantly reduced and lean body mass was significantly increased. The change in muscle CSA was not correlated with the changes in HbA1c or muscle strength. CONCLUSIONS: Strength training significantly improves both muscle mass and the muscle to fat ratio in T2DM. However, changes in muscle observed with computed tomography were not related to changes observed in HbA1c with training.

Implantation of paclitaxel-eluting stent impairs the vascular compliance of arteries in porcine coronary stenting model.

BACKGROUND: The impaired compliance of large and medium-sized muscular arteries has been shown to correlate with the risk of adverse cardiovascular events. We assessed coronary artery distensibility using simultaneous intracoronary ultrasound and pressure wire measurements in porcine coronary arteries after implantation of paclitaxel-eluting (PES) and bare metal stents (BMS) and compared this with the histopathology of the arterial wall injury. METHODS: PES and BMS were implanted into porcine left coronary arteries under general anesthesia. At 1-month follow-up (FUP) the endothelium-dependent and endothelium-independent vascular compliances were measured after intracoronary infusion of 10(-6)M acetylcholine for 2.5min, and intracoronary bolus of 100microg nitroglycerine, respectively. The arterial stiffness index, distensibility and reflexion index were calculated in stented arteries (n=25 PES and n=25 BMS), and correlated with histopathologic and histomorphometric changes of the vessel wall. RESULTS: In spite of smaller neointimal area, the fibrin deposition, medial thickening, vascular wall inflammation scores and arterial remodeling index were elevated and endothelialization was impaired in arteries with PES. Arteries with PES exhibited significantly worse endothelium-dependent vascular compliance: the stiffness (p<0.001) and reflexion index (p<0.001) were significantly higher and the distensibility index (p<0.001) lower as compared with the arteries with BMS. The endothelium-independent vascular reaction was similarly impaired in arteries with PES, as the stiffness index (p<0.001) and the distensibility index (p<0.001) differed significantly between the PES and BMS groups. Incomplete endothelialization (r=0.617, p<0.001) was significantly associated with the endothelium-dependent increased vascular stiffness. The increased fibrin score (r=0.646, p<0.001), vessel wall inflammation (r=0.657, p<0.001) and medial thickening (r=0.672, p<0.001) correlated significantly with the endothelium-independent stiffness index. CONCLUSIONS: Implantation of PES impairs the coronary artery wall structure and the endothelium-dependent and independent vessel wall dynamics more than does the implantation of BMS.

Association between the efficacy of dual antiplatelet therapy and the development of in-stent neointimal hyperplasia in porcine coronary arteries.

OBJECTIVE: We set out to compare the effectiveness of platelet aggregation therapy in association with the development of in-stent neointimal hyperplasia in porcine coronary arteries. METHODS: Thirty-two pigs underwent coronary stenting with bare-metal stents under general anaesthesia. One hundred milligrams of aspirin and loading doses of either 300 mg clopidogrel (group C, n=13) or 2 x 500 mg ticlopidine (group T, n=19) were administered before intervention. During the follow-up, the animals received a daily dose of 100 mg aspirin and 75 mg clopidogrel or 2 x 250 mg ticlopidine, respectively. After 4 weeks, the histopathological and histomorphometric parameters of the explanted stented coronaries were assessed. Levels of circulating cytokines and platelet activation factors were measured. ADP-induced and collagen-induced aggregation was measured immediately before stenting and then every 3rd day. The aggregation profiles were calculated and correlated with the histological parameters. RESULTS: The fibrin deposition scores and inflammation scores were higher in group T than in group C, with similar injury scores. Endothelialization was complete in both groups. A significantly lower neointimal area (1.08+/-0.36 vs. 1.58+/-0.5, group C vs. T, P=0.026) and percentage of area stenosis (29.8+/-12.1 vs. 44.3+/-16.3, group C vs. T, P=0.032) were observed in group C. The loading dose of clopidogrel significantly reduced the platelet activation parameters before the first angiography as compared with ticlopidone. Clopidogrel treatment resulted in a significantly better aggregation profile relative to ticlopidine (mean ADP-induced aggregation: 28.4+/-9.1 vs. 52.5+/-12.0%, P<0.001). Significant (P<0.05) positive linear correlations were observed between the ADP-induced aggregation profile and the neointimal area (r=0.584), percentage of area stenosis (r=0.666), inflammation (r=0.476) and fibrin deposition (r=0.496). CONCLUSION: The effectiveness of dual antiplatelet therapy plays an important role in the inhibition of in-stent neointimal hyperplasia.

The benefit of strength training on arterial blood pressure in patients with type 2 diabetes mellitus measured with ambulatory 24-hour blood pressure systems.

BACKGROUND: An ambulatory 24-hour BP-monitoring (ABPM) is of paramount importance, while patients are engaged in their usual activities, for a better representation of blood pressure (BP). ABPM provides not only automated measurements of brachial-artery pressure over a 24-hour period but also a highly reproducible circadian profile. The purpose of this investigation was to evaluate the effect of strength training (ST) on BP in patients with type 2 diabetes mellitus (T2D) and to obtain new and important information on BP profiles over 24-hour by using an ABPM. MATERIAL AND METHODS: We recruited ten patients (mean age: 59.7 +/- 7.3) from our Diabetes Department who participated in a 4-month systematic ST program on three non-consecutive days of the week. The ST program consisted of exercises for all major muscle groups. The numbers of sets for each muscle group were systematically increased from 3 at the beginning of the program to 4, 5 and finally 6 sets per week at the end of the program. The ABPM equipment (oscillometric Model Mobil-O-Graph CE 0434) was applied before and after 4-month training period. Routine HbA1C levels were measured using standard techniques. All subjects took a cycling test to measure maximum oxygen uptake (VO2peak) and maximum workload (Wmax) before and after the training period. Maximal strength was determined by one repetition maximum (1RM) in kp for the bench press, bench pull and leg press exercises, using the Concept 2 Dyno. RESULTS: Analysis of the pooled daytime and night-time data showed a significant reduction of mean arterial BP (from 93.8 +/- 19.2 to 90.6 +/- 14.3 mmHg; p > 0.01) after a 4-month ST (-3.4% mmHg). VO2peak (p < 0.05), Wmax (p < 0.05), 1RM for all muscle groups (p < 0.01), lean body mass (p < 0.05) and percent body fat (p < 0.05) improved significantly after a 4-month of ST. HbA1C showed a significant reduction by 14.5% (from 8.3 +/- 1.7 to 7.1 +/- 0.9%; p < 0.01). CONCLUSION: We found a significant reduction of mean arterial BP after a 4-month ST, measured by the ABPM system. These results demonstrate that ST may not only increase muscle strength but also decrease BP and perhaps the risk of future CVD development.

Time course of prothrombotic and proinflammatory substance release after intracoronary stent implantation.

We hypothesized that restenosis after coronary stenting is predicted by elevated levels of markers of thrombus formation and inflammation. Plasma levels of representative markers of inflammation, the thrombin and plasmin activation systems and adhesion molecules were measured in 59 patients with stable angina pectoris before, immediately after and 6 hours (h), 12 h, 24 h, one month and six months after elective stent implantation (radioactive phosphorus-32 stents/RSs/ n = 16, bare-metal stents/BMSs/ n = 43). All patients underwent clinical and angiographic follow-up (FUP) six months after stenting. RSs had significantly higher angiographic severity of restenosis than BMSs (47.1 +/- 20.1% vs. 27.6 +/- 22.0%, p = 0.003). Repeated measures ANOVA revealed significant differences between the BMS and RS groups as regards the increases in plasma levels of vascular cell adhesion molecule-1 (VCAM-1, p = 0.022), plasminogen activator inhibitor-1 (PAI-1, p = 0.047), tissue-type plasminogen activator (tPA, p = 0.047) and CD40 ligand (CD40L, p = 0.038). tPA levels tended to increase immediately after stenting in both groups, whereas the PAI-1 level one month after stenting was elevated significantly only in the RS group. In the RS group, the plasma levels of CD40L were increased at 24 h and six months after stenting, and the VCAM-1 level rose immediately after stenting and remained high during the FUP. Multivariate analysis on pooled laboratory data of both groups revealed elevated levels of VCAM-1 at 12 h and at six months as significant predictors of the severity of stent restenosis. In conclusion, the process of inflammation and thrombosis occurring after coronary interventions seems to be prolonged and enhanced in patients with high-grade restenosis at the follow up.

Small vessel stenting with cobalt-chromium stents (Arthos Pico) in a real world setting.

BACKGROUND: In current clinical practice, 35-67% of significant coronary artery lesions are located in small (<3.0 mm) vessels, a setting with poor short- and long-term results after percutaneous coronary interventions. OBJECTIVES: The aim of the present Arthos Pico Austria Multicenter Registry is to demonstrate the safety and efficacy of the Arthos Pico (cobalt-chromium alloy) stent implantation in small coronary arteries in a real world setting. METHODS: Two hundred and three patients (mean age, 67+/-12 years; 63% male) were included in the Registry; 199 patients (98%) were controlled clinically (including noninvasive stress tests) 6 and 12 months after stent implantation. Clinically driven angiographic controls were performed in 37 patients (18.2%) at mean 6 months after stenting. The primary endpoint of the study was the 6-month rate of major adverse cardiac events (as target vessel revascularization, all cause death, and acute myocardial infarction), the secondary endpoints were the intervention complications, and the occurrence of acute and subacute stent thrombosis. RESULTS: The procedural success was 99%. The rates of acute and subacute stent thrombosis were 0.5 and 1.5%, respectively. During the 6-month clinical follow-up, primary endpoint events (major adverse cardiac events) were recorded in 13% of the clinically controlled patients: four patients (2%) with acute myocardial infarction; 12 patients (6%) with target vessel revascularization; and 10 patients died (5%), resulting in an event-free survival rate of 87%. Between the 6- and 12-month follow-up, additional target vessel revascularization was performed in three patients, acute myocardial infarction and death occurred in one patient each, respectively. Thus, the 12-month major adverse cardiac event-free survival rate was 85%. Patients who died had older age (76+/-7 years) and a high proportion of type C lesions (50%) at the initial angiography. Multivariate analysis revealed older age (P=0.026) and type C lesions (P=0.016) as significant predictors for all causes of death. CONCLUSION: In conclusion, stenting of small arteries with Arthos Pico is safe and effective in the prevention of major adverse cardiac events during 6- and 12-month follow-up.

Effect of timing of clopidogrel administration on 30-day clinical outcomes: 300-mg loading dose immediately after coronary stenting versus pretreatment 6 to 24 hours before stenting in a large unselected patient cohort.

BACKGROUND: The aim of our prospective multicenter Clopidogrel Registry was to evaluate the efficacy and safety of a 300-mg loading dose of clopidogrel at the time of ad hoc stenting in patients with suspected coronary artery disease who were not pretreated with clopidogrel for any reason, and to compare the 30-day clinical event rates with the outcome of patients pretreated with a loading dose of clopidogrel 6 to 24 hours before stenting. METHODS: Between March 2002 and February 2004, 4160 consecutively included patients received a 300-mg loading dose of clopidogrel immediately after (group 1, n = 2679) or 6 to 24 hours before stenting (group 2, n = 1481). RESULTS: The primary end point (triple composite end point of acute myocardial infarction, all-cause death, and urgent repeat target vessel revascularization) at 30 days occurred in 4.74% versus 2.77% in groups 1 and 2, respectively (P = .002). The secondary end point events, the stent thrombosis, occurred significantly more frequently in group 1, with a trend toward increase in incidence of death, target vessel revascularization, or need for glycoprotein IIb/IIIa antagonists during percutaneous coronary intervention. Pretreatment with clopidogrel was associated with more major bleeding (secondary safety end point) (0.41% vs 1.35% in groups 1 and 2, respectively; P = .001). CONCLUSIONS: The results of our multicenter prospective Clopidogrel Registry demonstrate lower efficacy of a 300-mg loading dose of clopidogrel at the time of stenting compared with pretreatment 6 to 24 hours before percutaneous coronary intervention on the 30-day composite clinical end point in the large unselected patient cohort, which suggests the benefit of clopidogrel pretreatment in all incoming patients with suspected significant coronary artery disease scheduled for coronary angiography.

Platelet activation and high tissue factor level predict acute stent thrombosis in pig coronary arteries: prothrombogenic response of drug-eluting or bare stent implantation within the first 24 hours.

Increased thrombogenicity of drug-eluting stents (DESs) has recently been reported. The aim of the present study was to investigate the prothrombogenic effect of DESs and Bare stents, and determine factors predictive of acute stent thrombosis (AST) in preclinical experiments using new stent design or coating. Circulating pre- and post-stenting parameters of platelet activation (mean platelet volume, MPV; platelet distribution width, platelet large cell ratio), thrombin activation (thrombin-antithrombin complex, TAT and prothrombin fragments, F1+2), tissue factor antigen (TF-ag) and -activity (TF-act) and plasminogen activator inhibitor-1 (PAI-1) were measured in 141 consecutive pigs. Stent implantations were performed after pretreatment with aspirin and clopidogrel with unfractionated heparin anticoagulation. Nineteen pigs (groups AST-DES, n = 12; and AST-Bare, n = 7) died mean 6.3 +/- 2.9 h after stent implantation from AST. The remaining 122 control (C) pigs (groups C-DES, n = 76, and C-Bare, n = 46) survived the 1-month follow-up. Non-significantly elevated levels of post-stent F1+2 and TAT were measured in AST groups. Post-stenting MPV was increased significantly in the groups ASTDES and AST-Bare as compared with the groups C-DES and C-Bare (11.73 +/- 1.12 and 11.6 +/- 0.68 vs. 8.85 +/- 0.78 and 9.04 +/- 0.81 fL; p < 0.001), similarly to TF-ag (189.1 +/- 87.5 and 127 +/- 34.9 vs. 42.5 +/- 24.6 and 35.3 +/- 37.6 pg/ml; p < 0.001, respectively), Tfact (3.23 +/- 0.95 and 2.73 +/- 1.68 vs. 1.43 +/- 1.12 and 1.61 +/- 1.31 pM; p < 0.01, respectively) and PAI-1 (99.1 +/- 15.8 and 99 +/- 14.7 vs.53.4 +/- 40.2 and 46.9 +/- 42.4 ng/ml;p < 0.01, respectively). Multivariate analysis revealed elevated post-stenting plasma levels of TF-ag (p = 0.016) and MPV (p = 0.001) as independent risk factors for developing AST within the first 24 h in a porcine coronary stent model.

Paradoxical effects of aurintricarboxylic acid and RG-13577: acute thrombosis and in-stent stenosis in a passive-coated stent.

PURPOSE: To investigate if a platelet inhibitor (aurintricarboxylic acid [ATA]) and a heparin-mimicking antagonist (RG-13577) of basic fibroblast growth factor 2 (bFGF2) could be combined as a stable compound and attached to conventional bare metal stents to hinder thrombus formation and inflammatory reactions of stenting. METHODS: Fifteen domestic pigs were stented with RG-13577/ATA-coated (n=6), ATA-coated (n=12), and bare metal stents (n=12) in the left anterior descending (LAD) and left circumflex (LCX) coronary arteries. All surviving pigs were evaluated with contrast angiography and intravascular ultrasonography (IVUS) after 4 weeks. Histological analysis of the stented arteries was performed after hematoxylin-eosin staining. Tissue factor (TF) staining and scanning electron microscopy (SEM) were performed in animals with acute stent thrombosis. RESULTS: Five of the 6 animals receiving an RG-13577/ATA-coated stent experienced acute stent thrombosis, while no adverse events occurred in the animals of the other 2 groups. Follow-up angiography did not show significant in-stent stenosis in either bare or ATA-coated stents. However, histomorphometry revealed larger neointimal area (3.54+/-0.69 mm2 versus 1.82+/-0.27 mm2, p<0.05) and outward plaque area (1.56+/-0.34 mm2 versus 0.61+/-0.12 mm2, p<0.05) in ATA-coated stents. Three-dimensional IVUS analysis showed analogous results, with significantly larger neointimal volume and outward plaque volume in ATA-coated stents. There was a slight increase in TF staining around the stent struts, while SEM showed increased platelet adhesion and activity in RG-13577/ATA-coated stents versus the ATA-coated and bare metal stents. CONCLUSION: RG-13577/ATA-coated stents lead to acute stent thrombosis. The ATA coating alone did not lead to acute events, but resulted in higher neointimal hyperplasia and expansive remodeling. These results underline the importance of preclinical studies before using new coated stents in human arteries.

NOGA-guided analysis of regional myocardial perfusion abnormalities treated with intramyocardial injections of plasmid encoding vascular endothelial growth factor A-165 in patients with chronic myocardial ischemia: subanalysis of the EUROINJECT-ONE multicenter double-blind randomized study.

BACKGROUND: The aim of this substudy of the EUROINJECT-ONE double-blind randomized trial was to analyze changes in myocardial perfusion in NOGA-defined regions with intramyocardial injections of plasmid encoding plasmid human (ph)VEGF-A(165) using an elaborated transformation algorithm. METHODS AND RESULTS: After randomization, 80 no-option patients received either active, phVEGF-A165 (n=40), or placebo plasmid (n=40) percutaneously via NOGA-Myostar injections. The injected area (region of interest, ROI) was delineated as a best polygon by connecting of the injection points marked on NOGA polar maps. The ROI was projected onto the baseline and follow-up rest and stress polar maps of the 99m-Tc-sestamibi/tetrofosmin single-photon emission computed tomography scintigraphy calculating the extent and severity (expressed as the mean normalized tracer uptake) of the ROI automatically. The extents of the ROI were similar in the VEGF and placebo groups (19.4+/-4.2% versus 21.5+/-5.4% of entire myocardium). No differences were found between VEGF and placebo groups at baseline with regard to the perfusion defect severity (rest: 69+/-11.7% versus 68.7+/-13.3%; stress: 63+/-13.3% versus 62.6+/-13.6%; and reversibility: 6.0+/-7.7% versus 6.7+/-9.0%). At follow-up, a trend toward improvement in perfusion defect severity at stress was observed in VEGF group as compared with placebo (68.5+/-11.9% versus 62.5+/-13.5%, P=0.072) without reaching normal values. The reversibility of the ROI decreased significantly at follow-up in VEGF group as compared with the placebo group (1.2+/-9.0% versus 7.1+/-9.0%, P=0.016). Twenty-one patients in VEGF and 8 patients in placebo group (P<0.01) exhibited an improvement in tracer uptake during stress, defined as a >or =5% increase in the normalized tracer uptake of the ROI. CONCLUSIONS: Projection of the NOGA-guided injection area onto the single-photon emission computed tomography polar maps permits quantitative evaluation of myocardial perfusion in regions treated with angiogenic substances. Injections of phVEGF A165 plasmid improve, but do not normalize, the stress-induced perfusion abnormalities.

Characterization of hibernating myocardium with NOGA electroanatomic endocardial mapping.

Because the terms "hibernation" and "viability" are not interchangeable, the recognition of hibernating myocardium within viable segments remained elusive for NOGA electroanatomic endocardial mapping. The aim of the present study was to determine the characteristics of hibernating myocardium in NOGA mapping. Baseline and follow-up endocardial mapping, thallium-201 myocardial perfusion scintigraphy at rest, and contrast ventriculography were performed in 28 patients who had proved viable myocardium before and 7.3 +/- 2.5 months after percutaneous coronary intervention. Significantly improved regional wall motion in the revascularized territory (region of interest) was confirmed in 9 patients (group 1) at follow-up (from -2.11 +/- 0.87 to -1.48 +/- 0.43 SD/chord, p <0.05), whereas no change in regional wall motion was observed in 19 patients (group 2; from -2.56 +/- 0.88 to -2.79 +/- 0.91 SD/chord). Average normalized thallium uptake at rest increased significantly in groups 1 and 2 after revascularization. A trend toward increased unipolar voltages in the region of interest was observed in group 1 at follow-up (from 10.6 +/- 3.5 to 11.7 +/- 4.0 mV, p = 0.073), whereas no change was observed in group 2 (from 8.7 +/- 4.4 to 8.9 +/- 3.8 mV). A significant increase in local linear shortening was measured only in group 1 (from 7.5 +/- 5.2% to 10.3 +/- 3.9%, p <0.05). Hibernating myocardial segments exhibited significantly higher unipolar voltages and late thallium uptake at rest at baseline. Receiver-operator characteristic analysis showed a mean unipolar voltage of 9.0 mV (predictive accuracy 0.708, common sensitivity and specificity 72%) in the region of interest for prediction of functional recovery. In conclusion, for characterizing the hibernating myocardium within viable segments, NOGA endocardial mapping offers on-line guidance for percutaneous coronary and noncoronary myocardial revascularization.

Vascular remodeling in atherosclerotic femoral arteries: three-dimensional US analysis.

PURPOSE: To investigate the various modes of vascular remodeling of atherosclerotic femoral arteries and determine the associations between type of arterial remodeling and clinical data (age, sex, and medical history) and inflammatory parameters. MATERIALS AND METHODS: Intravascular ultrasonography (US) of the femoral arteries was performed in 50 patients with clinical symptoms of peripheral vascular disease. To determine the arterial remodeling mode (expansive remodeling [ER], involving compensatory enlargement of the artery, or constrictive remodeling [CR], involving vessel constriction during progression of atherosclerosis), the cross-sectional areas (CSAs) of the external elastic membrane (EEM), lumen, and plaque-plus-media were measured every 0.1 mm by using three-dimensional reconstruction. Clinical, laboratory, and intravascular US data were compared in the different remodeling groups (dominant ER, dominant CR, or mixed remodeling) by using analysis of variance supplemented by Tukey-Kramer tests. Multivariate analysis was performed to test independent variables predicting dominant ER. RESULTS: Intravascular US revealed the parallel existence of ER and CR in all patients: Increases and decreases in EEM in response to plaque growth could be observed within the same artery. ER dominated in 13 (26%) patients, and CR dominated in 11 (22%) patients: At least 80% of EEM CSAs were higher or lower than the mean of the EEM CSAs of the segments proximal and distal to the lesion. Patients with dominant ER had higher levels of serum C-reactive protein (CRP) compared with levels in patients with dominant CR and patients with mixed remodeling (1.62 mg/dL +/- 2.05 [standard deviation] vs 0.19 mg/dL +/- 0.33 and 0.21 mg/dL +/- 0.39, respectively, P < .005). Multivariate analysis revealed high CRP level to be a significant independent predictor for dominant ER (P < .01). CONCLUSION: The parallel existence of ER and CR was found in all patients with peripheral atherosclerosis, with a dominance of vessel expansion in 26% of patients. Higher plasma CRP level was associated with dominant ER.

Short- and long-term clinical outcome after various stent implantation: overview of the results of uni- and multicenter stent registries.

The present study reports the results of the short- and long-term outcomes of prospective uni- and multicenter stent registries: Palmaz-Schatz (n = 140 patients), Ave-Micro and GFX (n = 280), Multilink Duet (n = 340), Multilink Tetra (n = 192), and Carbo (n = 140) Stent Registries, as well as the predictors and angiographic cutoff points predicting major adverse cardiac events (MACE) after different stent implantations. Significant decrease in subacute stent thrombosis (from 2.9% to 0) and MACE (from 35% to 8.3%) occurred as the improved stents, optimized stent implantation technique, and new postintervention drug therapy were introduced. The changes of angiographic cutoff values (postintervention minimal lumen diameter and preintervention reference diameter: from 2.9 and 3.1 mm for Palmaz-Schatz to 2.5 and 2.8 mm for Multilink Duet, Multilink Tetra, and Carbo stents) and clinical and angiographic factors predicting MACE indicated the change of traditional restenosis paradigm and that progress in clinical practice might be able to counterbalance unfavorable lesion and intervention-related characteristics.

[Long-term results of percutaneous transmyocardial laser revascularization therapy at the University of Vienna Medical Center]. / Langzeitergebnisse der "Perkutanen transmyokardialen Laser-Revaskularisations-Therapie" am AKH Wien.

INTRODUCTION: Percutaneous transmyocardial laser revascularization (PTMR) was used for treating patients with therapy refractory angina pectoris who are not amenable for angioplasty or bypass surgery ("no-option patients"). The aim of this study was to evaluate the short- and long-term results of PTMR-interventions performed at the University of Vienna between February 1999 and May 2000. PATIENTS AND METHODS: Twenty-four "no-option" patients underwent PTMR. The chronically ischemic myocardial areas were determined by perfusion scintigraphy; after coronary angiography and contrast ventriculography 10 patients were treated with the Biosense laser using 3D-NOGA-mapping guidance and 14 patients with the Eclipse laser using biplane fluoroscopic guidance. After an average follow-up period (FUP) of 7.7 +/- 4.2 months, all patients underwent perfusion scintigraphy, coronary angiography and contrast ventriculography. Global and regional left ventricular (LV) function were calculated by the area-length method. RESULTS: The ischemic myocardial areas of the patients were treated with an average of 16 laser points. In one patient, an intramural hematoma caused by the Biosense laser catheter was observed, in another patient the ventricular wall was perforated by the Eclipse laser (both events were resolved conservatively); during the in-hospital stay 2 patients suffered from severe angina pectoris and in one patient a pacemaker was implanted. During the 7-month-FUP one patient had a myocardial infarction; in one patient a stent implantation, in another one coronary bypass surgery had to be performed (in not-lasered areas), 2 patients died. Thus, the composite MACE rate was 33.3%. Angina class improved significantly during the FUP, but a trend to deterioration of global ejection fraction was observed. The rest and late rest myocardial perfusion remained unchanged. CONCLUSION: While the angina class of the patients improved significantly, no significant change of myocardial perfusion but a trend to deterioration of LV function after the FUP were observed.