Diabetes mellitus and platelet function after administration of aspirin and a single 600 mg dose of clopidogrel.
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Biomedical subjects
Publications and source records attributed to A Schömig.
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Drug-eluting stents (DES) are playing an increasingly important role in the treatment of coronary artery disease. These new devices work by releasing controlled amounts of pharmacological agents with anti-restenosis properties at the implantation site. Most of them use polymer coating as a drug carrier, but concerns about long-term negative effects of a permanent polymer coating have stimulated the development of non-polymer DES or DES based on bioabsorbable polymers. Several randomized studies with DES have demonstrated their superiority over bare metal stents mostly in selected patients and lesion subsets. Accumulating evidence is showing significant differences in performance between currently used DES. These differences are more pronounced in complex, high-risk subsets of patients and lesions and should be considered during the process of DES selection for the individual patient. Interventional cardiologists have learned that patients who receive DES require a more prolonged antiplatelet therapy, but the optimal length and regimen are still unclear and further investigations are needed. Major advances in interventional cardiology have caused a dramatic shift away from aorto-coronary bypass surgery and an increase in the complexity of percutaneous coronary interventions. Observational and specifically designed randomized studies are currently addressing the issue of the role of DES in complex situations including in-stent restenosis, ostial and bifurcation lesions, chronic occlusions, small vessels, long lesions, saphenous vein grafts, multivessel disease, left main disease, acute myocardial infarction and diabetes mellitus. Although definitive answers are still to come from ongoing research, available data support the use of DES in most of these situations.
Percutaneous coronary interventions with the use of stents have become the mainstay treatment of patients with various clinical manifestations of coronary artery disease. Despite their remarkable success, restenosis has remained the major drawback and its prevention has absorbed intensive experimental and clinical research work. After the failure of multiple efforts with systemic use of various drugs, local application of antiproliferative and anti-inflammatory agents released by specially designed coated stents led to considerable suppression of neointima and opened new prospects in the prevention of restenosis. An increasing body of evidence is showing the advantages provided by drug-eluting stents (DES) in almost all subsets of patients with coronary artery disease with a drastic decrease in the need for reintervention. To date, the most commonly used and the only US Food and Drug Administration (FDA) approved DES are a sirolimus-eluting stent (Cypher) and a paclitaxel-eluting stent (Taxus), both of which are polymer-based DES and will constitute the focus of this review. Recent data demonstrate that DES are not equal in their safety and efficacy. A less optimistic aspect of DES technology are the reiterated concerns about a more prolonged risk of stent thrombosis. Although all agree on the need of a longer duration of dual antiplatelet therapy in patients treated with DES, its optimal length is still to be defined. Because polymers used for stent coating are often seen at the origin of the compromised long-term safety of DES, new technologies able to avoid permanent polymers may offer a valuable alternative.
In a recent study, analysis of gene expression in atherectomy specimens derived from restenotic coronary lesions revealed 223 differentially expressed genes. Thirty-seven of these genes indicated activation of interferon- (IFN-) gamma signaling in neointimal smooth muscle cells. Moreover, genetic disruption of IFN-gamma signaling in a mouse model of restenosis significantly reduced the vascular proliferative response. Thus, IFN-gamma is assumed to play an important role in the control of tissue proliferation during neointima formation. We hypothesized that genetic variants of IFN-gamma and its receptor subunits are involved in upregulation of IFN-gamma related genes in neointimal tissue of patients that develop in-stent restenosis. Polymorphisms in the genes encoding for IFN-gamma (IFNG T874A) and its receptors 1 (IFNGR1 C-56T) and 2 (IFNGR2 A839G) were tested for their association with restenosis. IFNG T874A, IFNGR1 C-56T and IFNGR2 A839G genotypes were determined in a consecutive series of patients (n=2591) that had been treated with coronary stents. Follow-up angiography 6 months after stent implantation was performed in 76.8% of the patients. Genotyping was performed with PCR-based methods. IFNG T874A, IFNGR1 C-56T and IFNGR2 A839G genotypes were not associated with the incidence of angiographic and clinical restenosis (P>0.23). Moreover, there was no association between IFNG, IFNGR1 and IFNGR2 genotypes and the combined incidence of death form any cause and non-fatal myocardial infarction during the first 12 months following the intervention (P>0.61). Thus, this study does not support a clinically relevant role of the studied polymorphisms in the processes leading to in-stent restenosis.
The relationship between volume and outcome in medicine has been intensively investigated in the last few decades. The large amount of accumulated data demonstrates that for many surgical or non-surgical procedures and medical conditions, patients being treated in high-volume hospitals or by high-volume physicians have lower mortality rates and better quality of life compared to those treated by low-volume hospitals or by low-volume physicians. Although the degree of the relationship between high volume and better outcome varies, it is persistent across a wide range of procedures and conditions. Percutaneous coronary interventions (PCIs) have an important impact on public health, given the frequency of coronary heart disease for which these procedures are performed. Studies carried out before and after the advent of stents on the relationship between volume and outcome for PCIs have almost consistently reported that performance of PCIs in high-volume institutions or by high-volume operators is associated with improved outcomes for patients, regardless of the specific indication for PCI. For those procedures for which a relationship between high volume and better outcome has been clearly demonstrated, patients as well as their referring physicians should be informed that patients can benefit both in terms of reduced mortality and improved quality of life if they are treated by high-volume health care providers. Consequently, for these procedures, a health care policy aiming at their concentration in high-volume institutions should be strongly considered.
Emery-Dreifuss muscular dystrophy (EDMD) is a common form of muscular dystrophy frequently involving cardiac muscle, thus leading to dilated cardiomyopathy. Clinical outcome and prognosis is frequently determined by the involvement of the cardiac conduction system causing symptomatic bradyarrhythmias, as well as tachyarrhythmias and, if untreated, frequent sudden cardiac death. Typical features of the cardiac involvement of EDMD are presented, caused by a novel missense mutation in the splice receptor sequence of intron 6 of the LMNA gene on chromosome 1, encoding for the lamin A/C gene, consistent with the autosomal dominant form of EDMD.
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Within the course of an acute posterior wall myocardial infarction there may be involvement of the right ventricle leading to right ventricular infarction. The long-term prognosis of patients with right ventricular infarction is not meaningfully compromised provided that the left ventricular function is preserved. However, in the acute phase, there may be a threefold increase in mortality if the right ventricular infarction leads to substantial right ventricular dysfunction. Consequently, right ventricular involvement should be detected as early as possible. In addition to the clinical presentation, the ECG and echocardiogram can provide decisive information. In addition to reperfusion, specific measures are employed to address the hemodynamic derangement of right ventricular dysfunction. These include administration of fluids for volume expansion to increase filling pressure and avoidance of vasodilators and diuretics.
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OBJECTIVE: The objective of this randomized trial was to assess the antirestenotic effects of phosphorylcholine (PC)-coated stents as well as of abciximab in small coronary arteries when compared with percutaneous transluminal coronary angioplasty (PTCA) and placebo respectively. BACKGROUND: Stent coating with PC has been shown to reduce protein absorption and platelet activation which may reduce the risk of restenosis. Furthermore, on the basis of nondedicated studies abciximab is believed to reduce the risk of restenosis after coronary interventions. METHODS: A total of 502 patients with lesions situated in small coronary arteries (vessel diameter </=2.5 mm) were randomly assigned to be treated with either PC-coated stents (n = 253) or PTCA (n = 249) and with either abciximab (n = 251) or placebo (n = 251) with the use of a 2 x 2 factorial design. All patients were pretreated with 600 mg clopidogrel. The primary end-point was the incidence of angiographic restenosis (>/=50% diameter stenosis) at follow-up; death or myocardial infarction, and target vessel revascularization (TVR), were assessed as secondary end-points. RESULTS: Angiographic restenosis did not differ between patients treated with PC-coated stents or with PTCA (39.0% vs. 34.2%; P = 0.30) and between patients receiving abciximab or placebo (39.3% vs. 34.3%; P = 0.29). Similarly, the need for TVR at 1-year follow-up did not differ between patients receiving PC-coated stents or PTCA (20.2% vs. 20.5%; P = 0.98) as well as between patients treated with abciximab or placebo (18.7% vs. 21.9%; P = 0.44). CONCLUSIONS: PC-coated stents and abciximab failed to reduce the incidence of angiographic restenosis after percutaneous coronary intervention of small coronary arteries. These data strengthen the belief that future studies on prevention of restenosis in small coronary arteries should focus on drug-eluting stents.
BACKGROUND: It is unknown, whether direct guidance by ultrasound is essential for the safety and efficacy of ultrasound-guided compression repair (UGCR) of pseudoaneurysms. We therefore tested, whether clinically guided manual compression repair (MCR) without continuous ultrasound control may represent an equally effective alternative. METHODS: After ultrasound diagnosis of a pseudoaneurysm, direct manual compression was applied to the lesion until the characteristic clinical signs disappeared or for a maximum of 1 hour. Then a compression bandage was applied for 24 hours. If the pseudoaneurysm persisted, MCR was repeated up to a maximum of three times. RESULTS: Of 96 consecutive patients with pseudoaneurysms, ten patients were referred to primary surgery; one patient refused any therapy. The remaining 85 patients (89%) were treated by MCR. MCR was successful in 74 patients (87%). Of these, 74% were cured at the first attempt, while 16% resp. 10% required 2 resp. 3 compression manoeuvers for definite cure. The success rate tended to be somewhat lower in patients on anticoagulants (78%) than in those on aspirin (91%) or those without any antithrombotic medication (89%) (p = 0.14). No major complications were observed. Of the 11 patients in whom MCR was unsuccessful, five patients underwent surgical repair; in four patients the pseudoaneurysms thrombosed spontaneously within 1-3 months and 2 pseudoaneurysms persist without complications. CONCLUSIONS: Our results with MCR are comparable to those published for UGCR. Since MCR requires less technical equipment and seems to be less painful for the patient, a prospective comparison of both methods appears warranted.
BACKGROUND: Myocardial capillary perfusion is a prerequisite of myocellular viability after reperfusion of acute myocardial infarction. It was hypothesised that the magnitude of myocardial capillary perfusion, assessed by transmural signal intensity in venous contrast echocardiography as a corollary of the blood volume of myocardial capillaries, and the amount of viable myocardium, represented by differential levels of contractile function two weeks after reperfusion, are correlated. OBJECTIVES: To evaluate the role of venous contrast echocardiography for the identification of viable myocardium in patients with acute myocardial infarction early after successful mechanical reperfusion. METHODS: 60 patients with a first acute myocardial infarction underwent venous contrast echocardiography several hours after successful mechanical reperfusion (median time interval 190 min.). The relative transmural videointensity (median (25th, 75th percentiles)) of akinetic segments was determined. After two weeks, contractile function was re-evaluated at rest and during dobutamine infusion if segments without functional recovery were present. RESULTS: Relative videointensity early after reperfusion differed significantly between functional groups after two weeks: normokinesia (88% (77%, 100%)), hypokinesia (74% (54%, 99%)), and akinesia with (61% (48%, 76%)) and without contractile reserve (31% (22%, 46%)). Relative videointensity and contractile function were significantly correlated (r = -0.67). The diagnostic accuracy of relative videointensity > 50% for prediction of contractility of initially akinetic segments at rest or during dobutamine was 82% (chi2 = 76.2, p < 0.001). CONCLUSIONS: Early after successful mechanical reperfusion of acute myocardial infarction, the magnitude of capillary perfusion in the perfusion territory of an infarct related artery is correlated with the amount of viable myocardium. Quantitative venous contrast echocardiography can be used for accurate identification of viable myocardium.
Cardiac myocyte apoptosis has been demonstrated in end-stage failing human hearts. The therapeutic utility of blocking apoptosis in congestive heart failure (CHF) has not been elucidated. This study investigated the role of caspase activation in cardiac contractility and sarcomere organization in the development of CHF. In a rabbit model of heart failure obtained by rapid ventricular pacing, we demonstrate, using in vivo transcoronary adenovirus-mediated gene delivery of the potent caspase inhibitor p35, that caspase activation is associated with a reduction in contractile force of failing myocytes by destroying sarcomeric structure. In this animal model gene transfer of p35 prevented the rise in caspase 3 activity and DNA-histone formation. Genetically manipulated hearts expressing p35 had a significant improvement in left ventricular pressure rise (+dp/dt), decreased end-diastolic chamber pressure (LVEDP), and the development of heart failure was delayed. To better understand this benefit, we examined the effects of caspase 3 on cardiomyocyte dysfunction in vitro. Microinjection of activated caspase 3 into the cytoplasm of intact myocytes induced sarcomeric disorganization and reduced contractility of the cells. These results demonstrate a direct impact of caspases on cardiac function and may lead to novel therapeutic strategies via antiapoptotic regimens.
Inflammatory mechanisms play an important role in the process of restenosis after percutaneous coronary interventions, with cell adhesion molecules, including Mac-1 (CD11b/CD18), as key mediators. A single nucleotide polymorphism, 1323C/T, located in exon 11 of the CD18 gene has been previously described, but its functional and clinical significances have not yet been studied. We assessed whether an association exists between this polymorphism and restenosis after coronary stenting. Clinical and angiographic measures of restenosis were evaluated over 1 year after coronary stent placement in 1,207 consecutive patients. Angiographic restenosis was defined as a > or =50% diameter stenosis at follow-up angiography. Determination of the CD18 1323C/T genotype was based on the polymerase chain reaction technique. The frequency of the T allele was 0.34 and its presence reduced the 1-year risk of a major adverse cardiac event (death, myocardial infarction, target vessel revascularization) by 29% (p = 0.011). Carriers of the T allele had a significantly lower risk of angiographic restenosis compared with noncarriers (odds ratio 0.71, 95% confidence interval 0.55 to 0.92). The incidence of restenosis decreased as a function of the number of T alleles: 38.1% in patients with genotype CC, 31.7% in patients with genotype CT, and 26.0% in patients with genotype TT (p = 0.004). Thus, the 1323T allele of the CD18 gene is associated, in a gene dose-dependent manner, with a lower incidence of angiographic restenosis after coronary stenting. This finding suggests that Mac-1 is involved in the development of restenosis after coronary stent placement.
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BACKGROUND AND OBJECTIVE: The electrocardiographic diagnosis of posterior myocardial infarction is difficult. It was the objective of the present study to evaluate ST-segment changes in angiographically documented occlusion of the left RCX in the setting of an acute myocardial infarction and to analyse the value of the posterior chest leads V(7)-V(9). PATIENTS AND METHODS: Data of 120 patients (88 males, on average 61+/-13 years old) with an acute myocardial infarction and angiographically proven occlusion of the left circumflex artery were included in the study. Mean time of pain onset to ECG recording was 5.5 +/- 2.8 hours. The ECGs were analysed for ST-segment changes of > or = 1 mm in two contiguous leads in surface leads I-aVF, > or = 2 mm in the precordial leads V(1)-V(6), and > or = 1 mm in right precordial (V(3)R-V(6)R) and posterior (V(7)-V(9)) leads. These additional leads were recorded only in a subgroup of 36 patients. Maximal creatine kinase activity was determined as a measure of infarct size. RESULTS: Standard leads I-V(6) showed ST-segment elevation in 55 of 120 patients (46 %). In the subgroup of patients with extended chest leads 61 % (11/36) had significant ST-segment elevation, whereas isolated ST-segment elevation in the posterior leads occurred in 8 % (3/36). ST-segment depression in the standard leads was observed in 73 of the 120 patients (54 %), and isolated ST-segment depression was seen in 31 patients (26 %). No significant ST-segment changes in the standard leads were found in 34 patients (28 %). Maximum CK values were not significantly different among the three groups (1107 +/- 815 IU/l vs 953 +/- 651 IU/l vs 816 +/- 553 IU/l; (P = 0.447). CONCLUSION: These findings confirm that the sensitivity of the standard ECG leads is less than 50 % in angiographically documented occlusion of the left RCX. The extended posterior chest leads (V(7)-V(9)) improve sensitivity only marginally (by 8 %). Isolated ST-segment depression or no significant ST-segment depression in the standard leads was observed in 26 % and 28 % respectively. The infarct size - as measured by maximum CK-values - did not differ among the respective groups.