T.W. Jax

Restenosis after elective coronary balloon angioplasty in patients with end stage renal disease: a case-control study using quantitative coronary angiography

Objective To assess the rate of angiographic restenosis in patients with end stage renal disease after elective coronary angioplasty. Design A retrospective case-control study of 20 patients with end stage renal disease and 20 sex and age matched controls without renal disease, who had undergone primarily successful coronary angioplasty. Control coronary angiography was performed regardless of worsening or renewed incidence of anginal symptoms. Main outcome measures Group comparison of coronary morphology, as evaluated by quantitative coronary angiography, and of cardiovascular risk factors. Results The rate of angiographic restenosis was 60% in patients with renal disease and 35% in controls. In patients with end stage renal disease the following differences (mean (SD) were found versus controls: raised plasma fibrinogen (483 (101)v 326 (62) mg/dl, p < 0.001); raised plasma triglyceride (269 (163) v 207 (176) mg/dl, p < 0.01); smaller diameter of the coronary reference segment (2.59 (0.87) v 2.90 (0.55) mm, p < 0.10); smaller minimum luminal diameter of the dilated stenosis (0.77 (0.46)v 0.97 (0.27) mm, p < 0.05). Discriminant analysis showed that minimum luminal diameter before angioplasty (r = −0.79) and fibrinogen (r = +0.34) had the highest statistical association with restenosis. Conclusions The high rate of angiographic restenosis in patients with end stage renal disease seems to be related to the size of the vessel dilated and to an increased prothrombotic risk, as indicated by higher fibrinogen concentrations.

Altered Blood Rheology in Obstructive Sleep Apnea as a Mediator of Cardiovascular Risk

Background: Cardiovascular complications are common in patients with obstructive sleep apnea (OSA). Blood rheology is a major determent of coagulation and an established risk factor for cardiovascular events. Since nocturnal hypoxemia could influence parameters of blood rheology, we hypothesized that OSA alters blood rheology independent of other cardiovascular risk factors. Methods: One hundred and ten consecutive patients admitted to the sleep laboratory were included. The association of plasma fibrinogen and viscosity (as parameters of blood rheology) with OSA was evaluated. Results: One hundred and ten patients aged 61.4 ± 10.1 years (body mass index 28.4 ± 4.1 kg/m2) were included. OSA was confirmed in 63 patients (57.2%) with an apnea-hypopnea index (AHI) of 28.7 ± 14.9 events/hour. Patients with OSA showed higher levels of plasma viscosity (1.36 ± 0.09 vs. 1.31 ± 0.08 mPas, p = 0.005). Nevertheless, hypertensive apneics have even higher levels of plasma viscosity than nonapneics (1.38 ± 0.091 vs. 1.32 ± 0.028 mPas, p = 0.018). Similar results were found in patients with coronary artery disease, where OSA was associated with elevated plasma viscosity (1.36 ± 0.076 vs. 1.31 ± 0.081 mPas, p = 0.007). Plasma fibrinogen was correlated with nocturnal minimal oxygen saturation (r = –0275, p = 0.0036) and AHI (r = 0.297, p = 0.001). OSA was associated with higher plasma fibrinogen (353 ± 83 vs. 317 ± 62 mg/dl, p = 0.015). These differences persist with control for cardiovascular risk factors. Conclusions: Patients with OSA have elevated morning fibrinogen levels and a higher plasma viscosity, which correlate positively with indices of sleep apnea severity. These changes in blood rheology are independent of cardiovascular risk factors, and therefore, might be specific mechanisms of OSA. This supports the pathophysiological concept that sleep apnea is a cardiovascular risk factor.

Incidence and clinical outcome of iatrogenic femoral arteriovenous fistulas: Implications for risk stratification and treatment

OBJECTIVES We sought to determine the incidence of arteriovenous fistulas (AVF), identify risk factors for AVF, and follow up the clinical outcome of femoral AVF. BACKGROUND Arteriovenous fistulas are a potential harmful complication of cardiac catheterization. Incidence and clinical outcome of iatrogenic AVF are unknown so far, although important for risk stratification and treatment. METHODS A total of 10,271 consecutive patients undergoing cardiac catheterization were followed up prospectively over a period of three years. Diagnosis of AVF was performed by duplex sonography. RESULTS The incidence of AVF was 0.86% (n = 88). The following significant and independent risk factors for AVF were identified: high heparin dosage (odds ratio [OR]) = 2.88), coumadin therapy (OR = 2.34), puncture of the left groin (OR = 2.21), arterial hypertension (OR = 1.86), and female gender (OR = 1.84). Within 12 months 38% of all AVF closed spontaneously. No signs of cardiac volume overload or limb damage were observed in patients with persisting AVF. None of the risk factors for AVF influenced the incidence or the rate of AVF closure. Only intensified anticoagulation showed a tendency to extend AVF persistence. CONCLUSIONS Almost 1% of patients undergoing cardiac catheterization acquire femoral AVF, for which patient- and procedure-related risk factors could be identified. One-third of iatrogenic AVF close spontaneously within one year. Cardiac volume overload and limb damage are highly unlikely with AVF persistence. Thus, a conservative management for at least one year seems to be justified.

Nitric oxide differentially regulates proliferation and mobilization of endothelial progenitor cells but not of hematopoietic stem cells

To investigate the role of nitric oxide in controlling endothelial progenitor (EPC) and hematopoietic stem cell (HSC) mobilization, wild-type mice, L-NAME treated WT and eNOS-/- mice received either PBS or G-CSF for 5 days. Under unstimulated conditions bone marrow of either L-NAME treated WT and eNOS-/- mice, representing acute and chronic NO-deficiency, showed higher CD34(+)Flk-I+ EPC numbers compared to their WT littermates. Furthermore, CD34(+)Flk-I+ progenitors under NO-deficient conditions showed a higher cell turn over since the proliferation and apoptosis activity under in vivo as well as in vitro conditions were enhanced. In line with this finding bone marrow derived EPC differentiation towards endothelial cells was modulated in an NO-dependent manner. Administration of G-CSF resulted in an increase of EPC within the bone marrow of WT animals with a consecutive release of these cells into the peripheral circulation. Under NO-deficient conditions G-CSF failed to increase EPC numbers. In contrast, the HSC population c-kit(+)Lin- was not influenced by nitric oxide. Thus, NO differentially supports the mobilization of the endothelial committed progenitor subpopulation in bone marrow but does not have an effect on HSC in vivo.

A prospective study on incidence and risk factors of arteriovenous fistulae following transfemoral cardiac catheterization

BACKGROUND A potentially harmful complication of cardiac catheterization is the arteriovenous fistula. Precise knowledge of possible factors predisposing for acquisition of iatrogenic AV-fistulae could enable cardiologists to perform a risk stratification for cardiac patients prior to catheterization. METHODS Over a period of 2 years, 10,271 consecutive patients who underwent cardiac catheterization were included in this study. Auscultation of a new femoral bruit was followed by a duplex scan to confirm the suspected diagnosis of an AVF. Every patient was investigated on the day after catheterization. RESULTS The incidence of iatrogenic AVF was 0.86%. A multivariate regression analysis revealed five significant and independent risk factors: (1) procedural heparin dosage >or=12,500 IU (Odds Ratio (OR)=2.88), (2) coumadin therapy (OR=2.34), (3) puncture of the left groin (OR=2.21), (4) arterial hypertension (OR=1.86) and (5) female gender (OR=1.84). Coronary angioplasty (instead of diagnostic procedure), size and number of sheaths, age and body mass index did not significantly affect the incidence of AVF. CONCLUSIONS The overall incidence of AV-fistulae following cardiac catheterization approximates 1%. Determination of significant risk factors will facilitate identification of patients at risk for iatrogenic arteriovenous fistulae prior to cardiac catheterization and thus help to develop strategies to reduce the incidence of AV-fistulae.

Refractory angina pectoris in end-stage coronary artery disease: Evolving therapeutic concepts ☆ ☆☆ ★

Refractory angina pectoris in coronary artery disease is defined as the persistence of severe anginal symptoms despite maximal conventional antianginal combination therapy. Further, the option to use an invasive revascularization procedure such as percutaneous coronary balloon angioplasty or aortocoronary bypass grafting must be excluded on the basis of a recent coronary angiogram. This coronary syndrome, which represents end-stage coronary artery disease, is characterized by severe coronary insufficiency but only moderately impaired left ventricular function. Almost all patients demonstrated severe coronary triple-vessel disease with diffuse coronary atherosclerosis, had had one or more myocardial infarctions, and had undergone aortocoronary bypass grafting (70% of cases). We present three new approaches with antiischemic properties: long-term intermittent urokinase therapy, transcutaneous and spinal cord electrical nerve stimulation, and transmyocardial laser revascularization.

Long-term intermittent urokinase therapy in patients with end-stage coronary artery disease and refractory angina pectoris: A randomized dose-response trial

OBJECTIVES This dose-response study was designed to test two low dose regimens of urokinase administered over a prolonged time period in patients with chronic refractory angina pectoris with respect to effects on clinical symptoms and objective variables of myocardial ischemia. BACKGROUND Patients with severe and chronic refractory angina pectoris in end-stage coronary artery disease represent an increasing clinical problem. Favorable therapeutic effects on myocardial ischemia have been reported for long-term application of low dose urokinase. METHODS Ninety-eight patients with chronic refractory and end-stage coronary artery disease were randomly assigned to two treatment groups: group A (49 patients) received 50,000 IU and group B (49 patients) 500,000 IU of urokinase as an intravenous bolus infection three times a week over a period of 12 weeks. Variables evaluated were number of weekly anginal events, data from ergometric exercise testing with simultaneous electrocardiographic registration, semiquantitative evaluation of Tc-99m 2-methoxy isobutyl isonitrile (MIBI) scans and rheologic variables. RESULTS After 12 weeks of treatment, anginal symptoms (events/week) were reduced significantly in group B by 70% compared with 24% in group A (p < 0.001). Fibrinogen decreased by 3% in group A and by 33% in group B (p < 0.001). Plasma viscosity and red blood cell aggregation were reduced by 6.4% (p < 0.001) and 19.9% (p < 0.001), respectively, in group B. Objective variables of myocardial ischemia were improved significantly in group B only. No cumulation of coronary ischemic events was observed in group B. CONCLUSIONS Long-term intermittent urokinase therapy in an applied dose of 3 X 500,000 IU/week represents an effective anti-ischemic and antianginal approach for patients with refractory angina pectoris and end-stage coronary artery disease. Apart from rheologic improvement, antithrombotic properties and plaque regression are likely anti-ischemic mechanisms.

Hemostatic risk factors in patients with coronary artery disease and type 2 diabetes - a two year follow-up of 243 patients

BackgoundThrombosis is regarded to be a key factor in the development of acute coronary syndromes in patients with coronary artery disease (CAD). We hypothesize, that hemostatic and rheological risk factors may be of major relevance for the incidence and the risk stratification of these patients.MethodsIn 243 patients with coronary artery disease and stable angina pectoris parameters of metabolism, hemostasis, blood rheology and endogenous fibrinolysis were assessed. Patients were prospectively followed for 2 years in respect to elective revascularizations and acute coronary syndromes.ResultsDuring follow-up 88 patients presented with cardiac events, 22 of those were admitted to the hospital because of acute events, 5 Patients were excluded due to non- cardiac death. Patients with clinical events were found to be more frequently diabetic and presented with a more progressed coronary atherosclerosis. Even though patients with diabetes mellitus demonstrated a comparable level of multivessel disease (71% vs. 70%) the rate of elective revascularization was higher (41% vs. 28%, p < 0.05). The results were also unfavorable for the incidence of acute cardiovascular events (18% vs. 8%, p < 0.01). In comparison to non-diabetic patients diabetics demonstrated significantly elevated levels of fibrinogen (352 ± 76 vs. 312 ± 64 mg/dl, p < 0.01), plasma viscosity (1.38 ± 0.23 vs. 1.31 ± 0.16 mPas, p < 0.01), red blood cell aggregation (13.2 ± 2.5 vs. 12.1 ± 3.1 E, p < 0.05) and plasmin-activator-inhibitor (6.11 ± 3.4 vs. 4.7 ± 2.7 U/l, p < 0.05).ConclusionPathological alterations of fibrinogen, blood rheology and plasminogen-activator-inhibtor as indicators of a procoagulant state are of major relevance for the short-term incidence of cardiac events, especially in patients with diabetes mellitus type 2, and may be used to stratify patients to specific therapies.

In vitro Bleeding Test with PFA-100TM—Aspects of Controlling Individual Acetylsalicylic Acid Induced Platelet Inhibition in Patients with Cardiovascular Disease

AbstractObjectives: This study investigated the usefulness and practicability of a platelet function analyzer (PFA-100TM, DADE-Behring, Germany) to determine individual platelet inhibition in patients treated with acetylsalicylic acid (ASA). Background: Patients with coronary artery disease (CAD) routinely and during angioplasty (PTCA) receive standard doses of ASA to avoid acute coronary syndromes and abrupt vessel closures without information of the individual efficacy of platelet inhibition. Methods: With the PFA-100TM a standardized bleeding time is measured. Whole-blood anticoagulated with 3.2% sodium citrate is aspirated through a capillary (⊘ 200μm) and through an aperture (⊘ 147μm). The time until occlusion of the aperture (closure time, CT) by a stable platelet plug induced by shear stress, collagen and epinephrine (COLL/EPI-CT) or shear stress, collagen and adenosine 5′-diphosphate (COLL/ADP-CT) is determined. To examine the usefulness of the PFA-100TM as a rapid bedside test and the individual effect of ASA, closure time was measured in healthy individuals (n=17), in patients with stable CAD (n=19) and in patients undergoing PTCA (n=8). Results: Patients with stable CAD and regular medication with 100mg ASA per day for at least 3 month showed shorter COLL/ADP-CT in comparison to healthy individuals who took only one single dose of 100mg ASA. Of the patients with CAD 63% had a COLL/EPI-CT within normal range suggesting a low or no response to ASA. Also only 50% of the patients undergoing PTCA reached the expected COLL/EPI-CT>300s after an additive single dose of 500mg ASA intravenously. Neither heparin, phenprocoumon, sex nor different blood sampling methods seem to influence the measurements relevantly. Conclusions: This pilot study indicates that with the PFA-100TM test device a simple and quick measurement of an in vitro bleeding time is possible. It is able to detect an increase in the bleeding time after a single dose of ASA 100mg in healthy subjects, reflecting a sensitive detection of ASA induced changes in platelet inhibition respective activation. Differences in the individual response to ASA could be observed in healthy subjects, patients with stable CAD and patients undergoing PTCA. Further studies should validate the PFA-100TM with standard methods to determine ASA response in patients with cardiovascular disease and investigate implications for treatment and outcome in this patient group.

Relevance of hemostatic risk factors on coronary morphology in patients with diabetes mellitus type 2.

ObjectiveThe influence hemostatitc parameters on the morphological extent and severity of coronary artery disease were studied in patients with and without DM type 2.BackgroundIt is known that patients with diabetes (DM) have abnormal metabolic and hemostatic parametersMethodsOf 150 consecutive patients with angiographically proven coronary artery disease 29 presented with DM. Additionally to parameters of lipid-metabolism fibrinogen, tissue-plasminogenactivator (t-PA), plasminogen-activator-inhibitor (PAI), plasmin-a-antiplasmin (PAP), prothrombin-fragment 1+2 (F1+2), thrombin-antithrombin (TAT), von-willebrand-factor (vWF), platelet factor 4 (PF4), glykomembranproteine 140 (GMP140) and the rheologic parameters plasma viscosity and red blood cell aggregation were evaluated. The extent and severity of CAD was evaluated according to the criteria of the American Heart Association.ResultsPatients with DM presented with a higher number of conventional risk factors as compared to non-diabetic patients. Additionally there were significant differences for F1+2, red blood cell aggregation and PAI. Diabetic patients showed a more severe extent of coronary arteriosclerosis, which also could be found more distally. A significant relationship between blood-glucose, thrombocyte-activation (vWF), endogenous fibrinolysis (PAI) and the severity of CAD and a more distal location of stenoses could be found (r = 0.6, p < 0.001).ConclusionPatients with coronary artery disease and DM type 2 showed marked alterations of metabolic, hemostatic, fibrinolytic and rheologic parameters, which can produce a prothrombogenic state. A direct association of thrombogenic factors on coronary morphology could be shown. This can be the pathophysiologic mechanism of more severe and distal pronounced coronary atherosclerosis in these patients.