The future of drug eluting stents.

In-stent restenosis (ISR) is the major drawback of percutaneous coronary interventions, occurring in 10-40% of patients. Drug eluting stents (DES) are successful in a large majority of patients in preventing restenosis for the first year after implantation. Recently, new stents have emerged that are loaded with anti-inflammatory, antimigratory, antiproliferative, or pro-healing drugs. These drugs are supposed to inhibit inflammation and neointimal growth and subsequently ISR. The future of DES lies in the development of better stents with new stent designs, better polymers including biological polymers and biological biodissolvable stent coatings, and new, better drugs.

[Costs and cost-effectiveness of Eptifibatide in the treatment of coronary ischemic syndromes. An analysis based on the PURSUIT study]. / Kosten und Kosteneffektivität von Eptifibatid in der Behandlung des akuten Koronarsyndroms. Eine Analyse auf Basis der PURSUIT-Studie.

AIMS: We analyzed whether using Eptifibatide plus heparin compared to heparin alone in patients with acute coronary ischemic syndromes is cost saving and/or cost-effective from the perspective of German hospitals. Our analysis is based on the clinical results of the PURSUIT study. MATERIALS AND METHODS: We conducted an incremental cost-consequence and cost-effectiveness analysis from the perspective of the admitting hospital. Costs refer to the initial hospitalization following the event. Incremental drug costs are based on a 72 hour infusion of Eptifibatide. Additional costs are analyzed as resulting from the management of complicating myocardial infarctions, including incremental days on the general ward or intensive care unit as well as necessary revascularization procedures. All costs are expressed in EURO (EUR). The estimated costs of managing ischemic complications are based on typical patterns seen in German hospitals. Our estimation of the life-years saved by using Eptifibatide is based on the DEALE method. All calculations are standardized to a hypothetical cohort of 100 treated patients. RESULTS: There are 0.064 saved life-years per patient. Cost-effectiveness of Eptifibatide is EUR 14,464 per life-year saved. CONCLUSION: Eptifibatide is cost-effective compared to other therapies in the treatment of acute coronary ischemic syndromes. The additional costs of using this substance should be reimbursed to the hospitals.

Population need for coronary revascularisation: are national targets for England credible?

OBJECTIVE: To estimate the need for coronary revascularisation, by using an incidence of indications approach, among 45-84 year olds with stable angina, unstable angina, and acute myocardial infarction. DESIGN: Modelling exercise. Six key steps along the pathway of care from initial diagnosis in primary or secondary care to revascularisation were defined and the frequency of indications estimated using routine data from hospital admissions and data from studies in the general population, and primary and secondary care. SETTING AND PATIENTS: Mid-1998 population of England. INTERVENTION: Coronary revascularisation. MAIN OUTCOME MEASURE: Ability to benefit (need), defined by randomised trials, expert panel ratings from the ACRE (appropriateness of coronary revascularisation) study, or by informal consensus. RESULTS: The need for coronary revascularisation was estimated to be 92 000 procedures, equivalent to a rate of 1861 per million population. Overall, the model of need exceeded current provision by 3.3:1, although among people aged 75 years and over the ratio was 7.7:1. A plausible upper estimate of need--obtained by assuming that 90% of patients with stable angina were referred from primary care and that angiography would be performed in 65% of patients with acute myocardial infarction and 75% of patients with unstable angina--was 2626 per million population. CONCLUSIONS: The national target of 1500 revascularisation procedures per million population is credibly related to population need, although upper estimates of need are considerably higher. Better understanding is required of the benefits of referring patients with specific indications from primary care. The greatest relative increase in provision is required for those aged 75 and older, among whom trial evidence of benefit is scant.

Non-invasive coronary angiography with high resolution multidetector-row computed tomography. Results in 102 patients.

AIMS: A new generation of multidetector-row CT (MDCT) scanners allows complete coronary coverage using retrospective ECG gating and 1mm slices. The purpose of this study was to investigate the potential of high resolution MDCT angiography with retrospective gating for detection of coronary artery stenoses. METHODS AND RESULTS: A total of 102 patients underwent both conventional and MDCT coronary angiography. After intravenous injection of a non-ionic contrast medium the entire heart was scanned within a single breath hold using 1mm slices. All MDCT data sets were reconstructed with retrospective gating at 20% to 80% in increments of 10% relative to the cardiac cycle. Two blinded independent reviewers analysed image quality for segments 1-4 (right coronary artery), 5-8 (left main, left anterior descending), and 11, 12 (left circumflex). These segments were evaluated for the presence or absence of significant (>or=50%) stenoses. The results were compared with those of invasive coronary angiography in a blinded fashion. Overall sensitivity for the detection of significant stenoses (>or=50%) were 0.86 (reader 1) and 0.93 (reader 2), specificity 0.96 (reader 1) and 0.97 (reader 2), negative predictive value 0.98 (reader 1) and 0.99 (reader 2). CONCLUSIONS: High resolution MDCT angiography with retrospective gating permits the non-invasive detection of coronary artery stenoses with high accuracy if image quality is optimized for each of the three major coronary arteries.

Virtual coronary angioscopy using multislice computed tomography.

BACKGROUND: With faster image acquisition times and thinner slice widths, multislice detector computed tomography (MSCT) allows visualisation of human coronary arteries with diagnostic image quality. In addition to conventional axial slices, virtual coronary angioscopies (VCA) can be reconstructed using MSCT datasets. OBJECTIVE: To evaluate the feasibility of reconstructing VCA and to determine the clinical value of this new application in detecting atherosclerotic coronary artery lesions. METHODS: Datasets obtained by contrast enhanced non-invasive coronary angiography using MSCT (Somatom VZ) were analysed from 14 consecutive patients. VCA were simulated in 14 coronary arteries (left anterior descending, n = 7; right coronary, n = 7). Lesion detection was undertaken on conventional contrast enhanced axial slices, as well as by VCA. Intracoronary ultrasound (ICUS) was used as the gold standard for in vivo plaque detection. RESULTS: 38 lesions were detected both on ICUS and on axial slices: 14 severe target lesions of > 75% area stenosis (11 calcified, three non-calcified), and 24 intermediate lesions of < or = 75% area stenosis (seven calcified, 17 non-calcified). Using VCA, all severe lesions (n = 14) and all calcified intermediate plaques (n = 7) could clearly be identified. However, non-calcified intermediate lesions (n = 17) could not be accurately distinguished from the vessel wall; they were recognised as vessel wall alterations without significant luminal narrowing. CONCLUSIONS: Current MSCT technology allows reconstruction of VCA with good image quality. Despite a more anatomical view of heart and coronary vessels on three dimensional reconstruction, conventional axial slices were found to be superior for detecting coronary lesions. Thus further technical innovations are required before VCA can become a useful technique in clinical cardiology.

Patients with acute coronary syndromes without persistent ST elevation undergoing percutaneous coronary intervention benefit most from early intervention with protection by a glycoprotein IIb/IIIa receptor blocker.

BACKGROUND: Many patients with acute coronary syndromes are offered percutaneous coronary intervention. However, the appropriate indications for, and optimal timing of, such procedures are uncertain. We analysed timing of intervention and associated events (death and myocardial infarction) in the PURSUIT trial in which 9461 patients received a platelet glycoprotein IIb/IIIa inhibitor, eptifibatide, or placebo for 72 h. Other treatment was left to the investigators. 2430 patients underwent percutaneous coronary intervention within 30 days. Four groups were distinguished, who underwent percutaneous coronary intervention on day 1; on days 2 or 3; at 4 to 7 days; or between 8 until 30 days, for eptifibatide- and placebo-treated patients. RESULTS: The four groups treated with placebo demonstrated total 30-day events of 15.9% for day 1 percutaneous coronary intervention, 17.7%, 15.0% and 18.2%, respectively, for successive intervals of later intervention. Later intervention was associated with more pre-procedural events (2.2% to 13.7%, P=0.001) which was balanced by a decrease in procedure-related events (12.1 to 3.1%, P=0.001), while the overall 30-day event rates were similar. Eptifibatide-treated patients with percutaneous coronary intervention on day 1 had the lowest rate of 30-day events (9.2%, P<0.05 vs other groups). In this group, pre-procedural risk was only 0.3%, while percutaneous coronary intervention on eptifibatide treatment was associated with low procedural risk (7.2%). The total 30-day event rate for later percutaneous coronary intervention in patients receiving eptifibatide was 14.0 on days 2 and 3, 15.0% for days 4 to 7 and 17.4% for days 7 to 30, respectively. CONCLUSION: Patients treated with a platelet glycoprotein IIb/IIIa receptor blocker, and early percutaneous coronary intervention (within 24 h) had the lowest event rate in this post hoc analysis. Thus 'watchful waiting' may not be the optimal strategy. Rather an early invasive strategy with percutaneous coronary intervention under protection of a platelet glycoprotein IIb/IIIa receptor blocker should be considered in selected patients. Randomized trials are warranted to verify this issue.

Localized pericardial tamponade: difficult echocardiographic diagnosis of a rare complication after cardiac surgery.

We report 2 cases of localized pericardial tamponade occurring soon after cardiac surgery, in which the diagnosis could not be made with transthoracic echocardiography. Computed tomography and transesophageal echocardiography, respectively, were necessary, and this underlies the importance of alternative imaging modalities when this condition is suspected. A high index of suspicion is crucial for reaching the correct diagnosis.

Local delivery of paclitaxel using the double-balloon perfusion catheter before stenting in the porcine coronary artery.

Paclitaxel is a new cancer chemotherapeutic agent that has been approved for clinical use in patients with a variety of different cancers. Paclitaxel inhibits cell proliferation by an action on microtubules. The aim of this study was to evaluate the safety and efficacy of locally delivered paclitaxel after coronary stent implantation. A novel double-balloon perfusion catheter was used to deliver the drug locally in the pig coronary artery. Twenty-seven domestic pigs underwent stent implantation of the left anterior descending artery. In the treatment group (n = 11), paclitaxel (10 ml; 10 micromol/l) was delivered using the double-balloon perfusion catheter prior to stent implantation. The control group received stent implantation only (n = 16). The animals were sacrificed 4 weeks later. Vessels were perfusion-fixed and morphometric analysis was performed using conventional techniques. In addition, the extent of injury was determined at each stent-strut area. Correlation of local injury and neointimal thickness was evaluated by linear regression. Neointimal thickness (paclitaxel 1.0 +/- 0.4 vs. control 0.7 +/- 0.3 mm), neointimal area (paclitaxel 4.1 +/- 2.2 vs. control 2.4 +/- 1.1 mm(2)), and the lumen area (paclitaxel 2.1 +/- 1.9 vs. control 2.5 +/- 0.9 mm(2)) did not show significant differences between both groups. Medial area (3.3 +/- 2.3 vs. 1.6 +/- 0.4 mm(2)) was larger in the vessels treated with paclitaxel (P < 0.05). Linear regression failed to show any difference in the response to injury between the two groups. Local delivery of paclitaxel with the double-balloon-perfusion catheter did not reduce neointima formation following stent implantation in native pig coronary arteries.

Noninvasive detection of coronary lesions by multislice computed tomography: results of the New Age pilot trial.

The reliable noninvasive assessment of coronary artery disease would constitute an important step forward in clinical cardiology. The aim of the New Age pilot trial was to evaluate the diagnostic accuracy of multislice computed tomography (MSCT) in determining coronary lesions. As a gold standard for in vivo plaque detection, intracoronary ultrasound (ICUS) was used. Forty plaques were detected by ICUS in 15 target vessels (LAD, n = 8; RCA, n = 7) in patients assigned for ICUS-guided PTCA. Preinterventional MSCT was performed in all patients and the results were compared to ICUS with regard to lesion detection and quantification. According to ICUS results, the 40 plaques were divided into three groups: group I, mild lesions < 50% (n = 14; 44.36% +/- 5.77%); group II, intermediate lesions 50%-75% (n = 12; 59.18% +/- 9.39%); and group III, severe lesions > 75% (n = 14; 91.47% +/- 3.68%). All MSCT scans showed sufficient image quality for analysis. Thirty of 40 (75%) plaques were detected by MSCT in a first blinded session. After unblinding the ICUS results, the remaining 10 (25%) plaques could be identified. Lesion severity was classified correctly in 34 of 40 (85%) plaques. Plaque calcifications were diagnosed correctly in 16 of 19 (84.2%) plaques. Quantification of vessel size revealed a good correlation to the ICUS results (r(2) 0.68; P = 0.004). Noninvasive MSCT angiography showed good diagnostic accuracy with regard to lesion detection and quantification of vessel size. The overall good image quality, makes this new technology a promising modality, which might become an alternative diagnostic approach in patients with known or suspected coronary artery disease. Cathet Cardiovasc Intervent 2001;53:352-358.

Use of intravascular ultrasound to compare effects of different strategies of lipid-lowering therapy on plaque volume and composition in patients with coronary artery disease.

BACKGROUND: We studied whether lipid-lowering therapy with atorvastatin (target LDL cholesterol [LDL-C] <100 mg/dL) compared with a moderate treatment regimen that used other lipid-lowering drugs led to a lesser progression of atherosclerosis and to different changes in plaque echogenicity in patients with coronary artery disease. METHODS AND RESULTS: This study was a 12-month, open-label, randomized, multicenter trial, which used serial 3D intracoronary ultrasound to calculate plaque volume and plaque echogenicity. After transcatheter therapy, 131 patients were randomized (atorvastatin n=65, usual care n=66). The target plaque had to be a minor lesion (ie, a diameter stenosis of <50% on angiography). After 12 months, mean LDL-C was reduced from 155 to 86 mg/dL in the atorvastatin group and from 166 to 140 mg/dL in the usual care group. Mean absolute plaque volume showed a larger increase in the usual care group compared with the atorvastatin group (usual care 9.6+/-28.1 mm(3), atorvastatin 1.2+/-30.4 mm(3); P=0.191). The hyperechogenicity index of the plaque increased to a larger extent for the atorvastatin group than for the usual care group, with a significant treatment effect for the percent change (atorvastatin 42.2%, usual care 10.1%; P=0.021). CONCLUSIONS: One year of lipid-lowering therapy to <100 mg/dL LDL-C most likely led to a slowdown of plaque growth of minor lesions. The significantly larger increase in plaque hyperechogenicity is most likely due to a change in plaque composition.

Accuracy and reliability of quantitative measurements in coronary arteries by multi-slice computed tomography: experimental and initial clinical results.

AIM: To evaluate the accuracy of non-invasive measurements within coronary arteries by multi-slice computed tomography (MSCT). We present experimental as well as clinical data. MATERIALS AND METHODS: Silicon tubes simulating coronary arteries (outer diameter 6 mm, lumen diameter within stenotic area 2 mm) were used for experimental studies. Clinical data were derived from 15 patients in whom vessel diameters were assessed by MSCT, intracoronary ultrasound (ICUS) and quantitative coronary angiography (QCA). MSCT were performed in a Somatom Volume Zoom(trade mark)CT system (Siemens, Forchheim, Germany) at 2 collimated slice widths (2.5 mm, 1.0 mm). RESULTS: Outer silicon tube diameters were overestimated by MSCT (6.56 mm +/- 0.32 mm). All measurements revealed significantly better results on 1.0 collimation compared to 2.5 mm collimation (outer diameter: 6.36 mm +/- 0.22 mm vs 6.76 mm +/- 0.27 mm, P < 0.0001; lumen diameters: 1.83 mm +/- 0.14 mm vs 1.51 mm +/- 0.19 mm, P < 0.0001). The comparison of vessel diameters within human coronary arteries revealed comparable results between ICUS and MSCT (4.89 mm +/- 0.67 mm vs 4.91 mm +/- 0.71 mm, P = 0.79, r = 0.79, P < 0.0001). QCA-measurements showed significantly lower results (3.67 +/- 0.71, P < 0.0001, r = 0.62, P < 0.001). CONCLUSIONS: Experimental as well as initial clinical results indicate acceptable reliability and accuracy of quantitative measurements by MSCT, when using thin collimated slice widths. Partial volume effects lead to a systematic overestimation of vessel size. MSCT has the potential to become an important non-invasive diagnostic tool in patients with coronary artery disease.

Inhibition of smooth muscle cell proliferation after local drug delivery of the antimitotic drug paclitaxel using a porous balloon catheter.

Percutaneous transluminal coronary angioplasty is an accepted treatment for coronary artery disease. The major limitation, however, is the high incidence of restenosis which limits the long-term benefit of this intervention. Paclitaxel is a new antiproliferative agent that has generated considerable scientific interest since it was introduced in clinical trials in the early 1980s. Recent in vitro studies have shown that paclitaxel has considerable antiproliferative activity in human coculture systems. In the present study the efficacy of paclitaxel was investigated after development of an intimal plaque by electrical stimulation and additional cholesterol diet and subsequent balloon angioplasty in 63 New Zealand White rabbits. Local drug delivery of paclitaxel was accomplished in 30 rabbits with a porous balloon catheter (35 holes, hole diameter 75 microm, 2.5 mm catheter diameter). Paclitaxel was administered locally with 4 ml (solution 10(-5) mol/L) using an injection pressure of 2 atm. To study the extent of restenosis and morphological changes, the animals were sacrificed 7, 28 or 56 days after intervention. After staining procedures quantification of SMC proliferation, intimal macrophages and morphological analyses were performed. Paclitaxel plasma concentrations were measured using HPLC technique. One week after balloon angioplasty the arteries treated with local paclitaxel delivery showed an insignificant trend towards a reduction in intimal smooth muscle cell proliferation (untreated 8.4 +/- 4.9 % vs paclitaxel treated 2.4 +/- 2.4 %, p = NS). However, this resulted in a significant reduction of stenosis degree of 66 % 8 weeks after intervention compared to the untreated group (untreated 41 +/- 18 % vs paclitaxel treated 14 +/- 11 %, p = 0.005). In conclusion, locally delivered paclitaxel prevented neointimal thickening in the rabbit carotid artery after balloon angioplasty. Local paclitaxel treatment may therefore be a clinical option for the prevention of restenosis after coronary interventions. However, further preclinical studies have to prove long-term efficacy and safety.

Primary cardiac leiomyosarcoma originating from the pulmonary valve. Case report and review of the literature.

Primary cardiac tumours are rare findings (incidence 0.02% according to a recent meta-analysis) with dismal prognosis. Approximately 25% are malignant, mostly represented by sarcomas. Among these, leiomyosarcomas are exceptional. Treatment for primary cardiac leiomyosarcomas consists of radical surgical resection followed by adjuvant radiation therapy and/or chemotherapy. The mean survival after surgery and adjuvant therapies is 6.8 months. We present a rare case of a 40- year-old male patient with a primary cardiac leiomysarcoma originating from the pulmonary valve. This patient died after surgery and implantation of a homograft of the pulmonary trunk. Furthermore, the literature has been reviewed.

Loss of cyclin A and G1-cell cycle arrest are a prerequisite of ceramide-induced toxicity in human arterial endothelial cells.

BACKGROUND: Ceramide is an important messenger of TNF- and lipid-induced apoptosis. We previously demonstrated the adverse effect of TNF in the process of reendothelialization as well as the dependence of its effect on cell-cycle regulation. The current study was designed to investigate the linkage between ceramide induced toxicity and growth arrest in human endothelial cells. METHODS AND RESULTS: Cultured human arterial endothelial cells (HAEC) served as an in-vitro model to test the cellular effects of C2-ceramide (C2). C2-induced cell death in HAECs occurred time- and dose-dependently. The LD(50) in subconfluent cells was three times lower than in confluent cell layers (25 vs. 75 microM). C2 caused up to 70% inhibition of BrdU and [3H]thymidine incorporation at non-toxic concentrations as a result of G1 cell-cycle arrest. Downregulation of cyclin A and p21(Cip1/Waf1) protein expression was observed independently of C2-toxicity, while expression of other cell-cycle regulatory genes was not affected. Inhibition of cyclin A protein expression by sequence-specific antisense-oligonucleotides was paralleled by significant growth-inhibition. The protein phosphatase inhibitor okadaic acid induced endothelial cell proliferation, which was completely abrogated by C2. In contrast, aphidicolin-synchronized endothelial cells demonstrated elevated cyclin A levels along with 30% higher BrdU-incorporation and 70% less C2-toxicity. G1-arrested cells, however, showed significantly enhanced C2-toxicity, lack of cyclin A expression and induction of uncleaved caspase-3 (CPP32). CONCLUSIONS: Ceramide abrogates endothelial cell proliferation independently of apoptosis or necrosis at low concentrations (

Self-rated health and clinical status after PTCA: results of a 4-year follow-up in 500 patients.

Background: Data on the clinical long-term outcome of patients with coronary artery disease in the years following percutaneous interventions are rare. We therefore decided to conduct a study to: (1) analyze the efficiency of a retrospective inquiry using a questionnaire and (2) perform a clinical long-term follow-up of our patients. Methods and results: Some 45+/-7 months after PTCA, a questionnaire was sent to 549 patients who had been treated at our institution from July 1, 1989, to June 30, 1991. The response rate was 91.1%, with 49 patients (8.9%) lost to follow-up. A total of 115/500 patients (23%) had reinterventions due to severe angina (69 patients (13.8%) undergoing re-PTCA and 46 (9.2%) CABG). Sixteen patients (3.2%) had a myocardial infarction and 35 patients (7.0%) died. Multivariate analysis revealed that patients who were asymptomatic 3 months after PTCA were likely to have a good long-term outcome. This was not found when comparing the clinical status immediately after PTCA to follow-up. Medical therapy with beta-blockers/aspirin/lipid-lowering drugs decreased from 75.2/82.2/35.4% at hospital discharge to 54.6/76.7/25.2% at follow-up. Conclusions: The present study provided important quality data for our institution. The response rate to the questionnaire was surprisingly high (91.1%), indicating that retrospective inquiries may also be efficient. The rate of reinterventions during long-term follow-up (23%) was acceptably low. Good self-rated health 3 months after the intervention turned out to be a strong predictor for a good clinical long-term outcome. Furthermore, we observed an underuse of cardiac medication, something that will be the subject of further quality improvement measures.

Noninvasive detection and evaluation of atherosclerotic coronary plaques with multislice computed tomography.

OBJECTIVES: The aim of the present study was to evaluate the accuracy in determining coronary lesion configuration by multislice computed tomography (MSCT). The results were compared with the findings of intracoronary ultrasound (ICUS). BACKGROUND: The risk of acute coronary syndromes caused by plaque disruption and thrombosis depends on plaque composition rather than stenosis severity. Thus, the reliable noninvasive assessment of plaque configuration would constitute an important step forward for risk stratification in patients with known or suspected coronary artery disease. Just recently, MSCT scanners became available for general purpose scanning. Due to improved spatial and temporal resolution, this new technology holds promise to allow for differentiation of coronary lesion configuration. METHODS: The ICUS and MSCT scans (Somatom Volume Zoom, Siemens, Forchheim, Germany) were performed in 15 patients. Plaque composition was analyzed according to ICUS (plaque echogenity: soft, intermediate, calcified) and MSCT criteria (plaque density expressed by Hounsfield units [HU]). RESULTS: Thirty-four plaques were analyzed. With ICUS, the plaques were classified as soft (n = 12), intermediate (n = 5) and calcified (n = 17). Using MSCT, soft plaques had a density of 14 +/- 26 HU (range -42 to +47 HU), intermediate plaques of 91 +/- 21 HU (61 to 112 HU) and calcified plaques of 419 +/- 194 HU (126 to 736 HU). Nonparametric Kruskal-Wallis test revealed a significant difference of plaque density among the three groups (p < 0.0001). CONCLUSIONS: Our results indicate that coronary lesion configuration might be correctly differentiated by MSCT. Since also rupture-prone soft plaques can be detected by MSCT, this noninvasive method might become an important diagnostic tool for risk stratification in the near future.