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Background: Patients with refractory angina pectoris in end-stage coronary artery disease represent a severe condition with a higher reduction of life-expectancy and quality of life as compared to patients with stable coronary artery disease. It was the purpose of this study to invasively re-evaluate highly symptomatic patients with formerly diagnosed refractory angina pectoris in end-stage coronary artery disease for feasible options of myocardial revascularization.Methods: Thirty-four patients formerly characterized as having end stage coronary artery disease with refractory angina pectoris were retrospectively followed for coronary interventions.Results: Of those 34 patients 21 (61.8%) were eventually revascularized with percutaneous interventional revascularization (PCI). Due to complex coronary morphology (angulation, chronic total occlusion) PCI demanded an above-average amount of time (66 +/- 42 minutes, range 25-206 minutes) and materials (contrast media 247 +/- 209 ml, range 50-750 ml; PCI guiding wires 2.0 +/- 1.4, range 1-6 wires). Of PCI patients 7 (33.3%) showed a new lesion as a sign of progression of atherosclerosis. Clinical success rate with a reduction to angina class II or lower was 71.4% at 30 days. Surgery was performed in a total of8 (23.5%) patients with a clinical success rate of 62.5%. Based on an intention-to-treat 2 patients of originally 8 (25%) demonstrated clinical success. Mortality during follow-up (1-18 months) was 4.8% in patients who underwent PCI, 25% in patients treated surgically and 25% in those only treated medically.Conclusion: The majority of patients with end-stage coronary artery disease can be treated effectively with conventional invasive treatment modalities. Therefore even though it is challenging and demanding PCI should be considered as a first choice before experimental interventions are considered. [ABSTRACT FROM AUTHOR]

Background: Thrombosis 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., Methods: In 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., Results: During 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)., Conclusion: Pathological alterations of fibrinogen, blood rheology and plasminogen-activator-inhibitor 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.

Objective: The influence hemostatitc parameters on the morphological extent and severity of coronary artery disease were studied in patients with and without DM type 2., Background: It is known that patients with diabetes (DM) have abnormal metabolic and hemostatic parameters, Methods: Of 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., Results: Patients 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)., Conclusion: Patients 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.

Background: Secondary coronary thrombus formation is considered to be co-factor in the pathogenesis of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Therefore systemic factors indicating a hypercoagulable disease state may be relevant for the process of coronary renarrowing. Even though experimental data suggest that in particular thrombin may be of major relevance for restenosis induced by mechanical injury, only little clinical data has been presented so far., Methods and Results: In 60 consecutive patients, who had been clinical stable for at least 2 months, and who underwent elective and primarily successful PTCA, follow-up films were evaluated by means of quantitative coronary angiography in respect to a categorical and a continuous definition of restenosis, luminal narrowing >50% and late luminal loss respectively. Of the chosen laboratory variables prothrombin fragment 1+2 (1.3+/-0.5 vs. 0.9+/-0.4 mmol/l, p<0.001) red blood cell aggregation at low shear stress (13.5+/-2.9 vs. 11.6+/-2.8 units, p<0.05), and plasminogen-activator inhibitor (3.7+/-1.8 vs. 5.3+/-3.2 U/ml p<0.05) differentiated between patients with (n=18) and without restenosis (n=42). Late luminal loss correlated positively with prothrombin fragment 1+2 (r=0.41, p<0.001), plasminogen-activator inhibitor (r= -0.28, p<0.05) and plasmin-alpha2-antiplasmin complex (r=0.39, p<0.01)., Conclusions: A hypercoagulable disease state and in particular thrombin generation characterize a high-risk group prone for restenosis in clinically stable coronary artery disease.

History and Clinical Findings: A 69-year-old female patient was admitted to a hospital for severe dyspnoea. It was conspicuous that shortness of breath and cyanosis only occurred in upright and completely disappeared in the supine position. This finding was objectified by pulse oximetry which demonstrated a decrease of arterial oyxgen saturation from 96 % in the supine to 86 % in the upright position., Investigations: After exclusion of other diseases the diagnosis of platypnoe- orthodeoxia syndrome as a result of a patent foramen ovale (PFO) was established., Treatment and Course: Cardiac catheterization in the upright and the supine position documented a high-grade right-to-left shunt of 31 % proportionally to systemic circulatory volume in the upright position with subsequent critical reduction of pulmonary perfusion to 1.4 l/min/m (2) (reference value > 2.2 l/min/m (2)) as the cause of dyspnoea. Catheter-based occlusion of the PFO was chosen as causal treatment modality. After that arterial oxygen saturation remained constant at 95 % in the supine and upright position and symptoms improved., Conclusions: Platypnoe-othodeoxia syndrome is a very rare syndrome but it can be substantiated by pathognomonic case history, clinical examination and simple machine-aided examinations. With a causative PFO a causal and save therapy is available.

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.

Objectives: This study investigated the usefulness and practicability of a platelet function analyzer (PFA-100(TM), 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-100(TM) a standardized bleeding time is measured. Whole-blood anticoagulated with 3.2% sodium citrate is aspirated through a capillary ( solidus in circle 200 microm) and through an aperture ( solidus in circle 147 microm). 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-100(TM) 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 100 mg 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 100 mg 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>300 s after an additive single dose of 500 mg 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-100(TM) 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 100 mg 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-100(TM) with standard methods to determine ASA response in patients with cardiovascular disease and investigate implications for treatment and outcome in this patient group.

Unlabelled: This study was designed to determine the effect of successful coronary revascularisation on left ventricular diastolic function., Methods: We consecutively studied the time course of diastolic function by Doppler echocardiography in 100 patients with one-vessel disease before and 48 hours after elective coronary angioplasty. Three abrupt vessel closures occurred within 24 hours after intervention. These three patients were excluded from the study. 58 patients were initially successful treated with coronary angioplasty (residual stenosis < 40%). In 39 patients stents were used to improve an inadequate result after coronary angioplasty. The following parameters of left ventricular diastolic function were evaluated before and 48 hours after coronary intervention: peak early (VE, m/s) and peak late diastolic (VA, m/s) flow velocity, E/A ratio, acceleration time (AT, ms), deceleration time (DT, ms) and isovolumetric relaxation time (IVRT, ms). Ejection fraction (EF; %) was determined and used to characterise systolic left ventricular function., Results: Both patient groups (58 patients with coronary angioplasty and 39 patients with combined coronary angioplasty and stent implantation) showed no relevant differences concerning sex, age, atherosclerotic risk factors, exercise capacity and results of exercise electrocardiography. All patients who underwent stent implantation showed an early improvement of left ventricular diastolic function 48 hours after revascularisation. Surprisingly there was no significant short-term improvement (48 hours) of diastolic function in patients with initially successful angioplasty., Conclusion: We suppose that stent implantation faster normalises coronary blood flow than coronary angioplasty.

Background: Patients with end-stage renal disease have an increased risk of developing coronary artery disease (CAD). The cardiovascular mortality of dialysis patients is 10-15 times higher compared with the general population. The aim of our study was to evaluate the morphological progression of coronary arteriosclerosis in this cardiovascular high-risk group by visual assessment and quantitative coronary angiography. Methods and results. In 26 patients with chronic renal failure (age, 47+/-11 years; 15 male; duration of dialysis, 23+/-25 months) the severity of CAD and degree of coronary stenoses were assessed in two coronary angiograms after a mean follow-up interval of 30+/-15 months (12-60). Baseline angiography revealed CAD in 13/22 patients (59%). The second angiography was performed as screening procedure prior to renal transplantation (n=20) and/or as follow-up angiography after coronary angioplasty (n=10). Visual assessment showed a progression defined by the development of haemodynamically relevant stenosis of >50% luminal diameter in 13 patients. Quantitative angiographic evaluation was performed in a total of 45 segments showing >25% narrowing at the second angiogram. A progression (>15% luminal reduction) was found in 17 of 45 segments, a new lesion (initial luminal diameter <20%) was detected in nine segments, resulting in progression or new lesion in 16 patients (62%). Patients with or without progression did not differ in age, duration of dialysis treatment, number of cardiovascular risk factors, or serum total cholesterol and fibrinogen levels. After percutaneous transluminal coronary angioplasty (PTCA) a restenosis was seen in seven of 16 primarily successfully dilated segments. After the second angiography, myocardial revascularization was performed in eight patients (1 PTCA, 7 coronary artery bypass graft)., Conclusions: Patients with end-stage renal disease have a high prevalence of CAD. In line with the clinical course, CAD patients on maintenance dialysis undergo rapid angiographic progression of CAD, which results in a high rate of subsequent myocardial revascularizations.

Introduction: During pregnancy eminent cardiovascular changes occur. The aim of the following study was to investigate the course of hemodynamic parameters under increased volume load during pregnancy in women suffering from mild arterial hypertension., Methods: Altogether 47 women (age: 25 +/- 4 years) with mild arterial hypertension detected during pregnancy underwent echocardiography at the 9th, 24th and 33rd week of gestation. Furthermore echocardiography was performed postpartum at weeks 1 and 8. The control group comprised 45 healthy pregnant women. In all patients left ventricular muscle mass index and systolic shortening fraction were measured. The following Doppler echocardiographic parameters were ascertained: peak early diastolic and peak late diastolic flow, VE/VA ratio, acceleration time, deceleration time and isovolumetric relaxation time., Results: During pregnancy all patients had an increase of left ventricular muscle mass index and a decrease of fractional shortening. All patients developed a relevant diastolic dysfunction. While the control group developed signs of disturbed relaxation as reduction of peak early diastolic flow (0.89 +/- 0.07 versus 0.82 +/- 0.08 m/s*), VE/VA ratio and an increase of isovolumetric relaxation time (72 +/- 12 versus 123 +/- 7*) at the 33rd week of gestation (* p < 0.01), all pregnant women with mild arterial hypertension developed a diastolic dysfunction with signs of delayed relaxation already at the beginning of gestation. 26 pregnant women with arterial hypertension developed a restrictive diastolic filling pattern at 24 weeks of gestation. The other 21 pregnant women only showed restriction for a short time at the end of gestation. In healthy pregnant women, volume load results in a reversible physiologic left ventricular hypertrophia, a significant alteration of diastolic left ventricular function in terms of a disturbed relaxation pattern and a temporary decrease of systolic function. In comparison hypertensive pregnant women show a delayed relaxation at the beginning of pregnancy and 50% developed early signs of restrictive cardiomyopathy. These changes may predispose to critical complications during pregnancy.

Patients with dilated cardiomyopathy (DCM) generally have an impaired functional capacity and poor long-term out-comes. A mortality of 5-15% per year has been described actually. Aim of this study was to verify the prognostic relevance of invasive and non-invasive parameters of diastolic function in patients with DCM. In 33 patients with DCM, cardiac catheterization was performed and left ventricular systolic (ejection fraction (EF; %)); left ventricular enddiastolic pressure (LVEDP; mmHg) and diastolic function (time constant of relaxation (T, ms); the constant of myocardial stiffness (b) were derived from biplane laevocardiography and simultaneous micromanometric registration of pressure-volume curves. For evaluation of clinical out-come, the follow-up period was defined as beginning on the day after cardiac catheterization and ending on the most recent date or with a cardiac event (death or cardiac transplantation). All patients were reevaluated for NYHA functional class and completed a standard questionnaire. The following hemodynamic parameters were evaluated: invasive parameters of left ventricular diastolic function (constant of relaxation: tau (ms), constant of myocardial stiffness: b)), as well as parameters of systolic function (ejection fraction (EF; %)), left ventricular pressure (LVEDP; mmHg), left ventricular muscle mass index (LVMMI; g/m2), left ventricular enddiastolic volume index (LVEDVI; ml/m2) and non-invasive parameters of morphological data, left ventricular systolic (fractional shortening (FS, %) and ejection fraction) and diastolic parameters with echocardiography. During the follow-up period of 36 months, 11 of 33 patients experienced a major cardiac event (cardiac death n = 8, heart transplantation n = 3). The major cause of death was progressive pump failure. The remaining 22 patients were further classified with respect to changes in functional status. While clinical symptoms could be improved medically in patients with moderate increase of myocardial stiffness, patients with severe increase of myocardial stiffness (b: 76.1 +/- 12.1 vs 17.9 +/- +8.1, p < 0.001) could not be improved and suffered more cardiac events. Doppler echocardiographic measurements in these patients showed a restrictive filling pattern (VE 0.91 +/- 0.21 vs 0.64 +/- 0.18 m/s; p < 0.01; VA 0.52 +/- 0.23 vs 0.57 +/- 0.24 m/s; p < 0.01, deceleration time 129 +/- 17 vs 211 +/- 14 ms; p < 0.01). The medical heart failure therapy was comparable in both groups. In patients with cardiac events, the diastolic left ventricular variables did not significantly differ between patients who underwent heart transplantation and those who died. Patients who demonstrated a sole impairment of relaxation (tau: > 50 ms) suffered no cardiac events. Impaired diastolic function contributes to the clinical picture of congestive heart failure. Parameters of left ventricular diastolic function are powerful and important predictors of major cardiac events in patients with DCM, like heart transplantation and non-sudden death, and may indicate future clinical success of medical treatment. Invasive and non-invasive parameters of diastolic function reveal comparable information for the estimation of prognosis of patients with DCM in order to initiate early therapy.

Background: Ischemic heart disease is the major cause of death in patients with end-stage renal disease. The high prevalence of coronary artery disease results in a rising number of dialysis patients requiring myocardial revascularisation., Objective: The objective of this study was to compare the outcomes of recurrent angina, myocardial infarction, rate of reinterventions and cardiovascular death following percutaneous coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) in patients with end-stage renal disease., Patients and Methods: In a retrospective investigation 40 patients with chronic renal failure undergoing primarily PTCA and 65 patients undergoing CABG were included. Both groups were comparable for gender, duration on dialysis and the number of cardiovascular risk factors per patient. Patients undergoing PTCA were younger (53 +/- 12 years vs. 57 + 8 years; p < 0.05) and more often diabetics (30% vs. 14%; p < 0.05)., Results: Most patients in both groups had a multi-vessel disease (95% in the CABG group vs. 74% in the PTCA group), in the CABG group there were significantly more patients with a triple-vessel disease (62% with vs. 40% in the PTCA group; p < 0.01), PTCA was primarily successful in 95% of the patients while complete revascularization was achieved in 88% of patients undergoing CABG. The perioperative mortality after CABG was 4.8% as compared to none after interventional revascularisation. The cumulative freedom of angina after 6, 12 and 24 months after intervention was significantly lower after PTCA (54%, 40%, 29%) than after bypass grafting (97%, 94%, 90%, p < 0.001). The frequency of reinterventions following PTCA was significantly higher compared to patients following CABG (p < 0.001). After PTCA 15 patients needed further revascularisations, 8 of them underwent CABG, whereas after CABG only two patients required additional myocardial revascularisation. There was no significant difference in the overall mortality between both groups; the survival rate after 12 and 24 months was 95% and 82% after PTCA and 93% and 86% after CABG, respectively., Condition: Although patients receiving CABG had a more severe coronary artery disease the overall mortality was comparable and clinical and functional outcome was improved compared to patients after coronary angioplasty.

We report a patient who underwent bilateral internal thoracic artery implantation into the myocardium known as a Vineberg procedure 27 years ago. Coronary angiography and Doppler echocardiography revealed patent grafts with total occlusion of all native coronary arteries. We measured flow velocities at rest and under stress conditions with noninvasive ultrasonic Doppler echocardiography. The flow patterns in both grafts were biphasic as in native coronary arteries. Under stress conditions no increase in flow was detectable as a marker of end-stage coronary artery disease with refractory angina pectoris.

Background and Objective: Although coronary heart disease (CHD) is a major cause of morbidity and mortality, it is still being underestimated in women. This prospective study was undertaken to ascertain special features of the symptoms and in the initial diagnosis of CHD in women., Patients and Methods: Between January 1996 and August 1998, a total of 5000 patients (2500 women, 2500 men; mean age 61 [39-83]) were admitted for their initial invasive investigation of suspected CHD. All data relating to history, laboratory tests, resting and exercise ECG, and coronary angiography were recorded and analysed., Results: Typical angina pectoris as initial symptom was recorded in 40% of women, 57% of men, atypical symptoms in 48% vs. 24%. Typical angina pectoris in the presence of demonstrated CHD were found in 32% of women, compared with 69% in men. The interval from initial symptoms to established diagnosis was 68 months in women and 9 months in men, 71% of women but only 5% of men having consulted at least two specialists. Both women and men with CHD had comparable risk factors. Anginal symptoms prematurely ended an exercise ECG test in 49% of women and 44% of men. Significant S-T segment changes were noted in 19% of women, 30% of men with CHD. The positive predictive value of clinical symptoms and ergometric results with regard to CHD was much lower in women than in men: 33% vs 85%., Conclusions: Clinical symptoms and the exercise ECG are much less diagnostically reliable in women than in men and had a very low predictive value. Women often have typical anginal symptoms even in the absence of CHD. They, therefore, require more sensitive methods than the exercise ECG for the initial diagnosis of CHD, especially in the face of prolonged symptom-to-diagnosis intervals.

Background and Objective: During pregnancy many substantial changes occur in the cardiovascular system. Aim of this study was to examine how physiological preload alterations influence left ventricular haemodynamic parameters., Patients and Methods: During the 9th, 24th and 33rd weeks of pregnancy and 8 weeks after childbirth 36 patients underwent echocardiographic studies. 36 young not pregnant women (25 +/- 7 years) served as controls. The following Doppler echocardiographic parameters were measured: peak early diastolic flow velocity (VE, ms); acceleration (AT; ms) and deceleration time (DT; ms) of flow velocity in early diastole; peak late diastolic flow velocity (VA; m/s) and isovolumetric relaxation time (IVRT; ms). In all women the left ventricular muscle mass index (LVMMI), fractional shorting (FS; %) and the ratio between septum and posterior ventricular wall were calculated., Results: During pregnancy all women showed an elevation of the left ventricular muscle mass index (LVMMI: from 66 +/- 6 to 100 +/- 9 g/m2; p < 0.01) and a decrease of fractional shortening (FS: from 38 +/- 4 to 31 +/- 3%). All patients developed a relevant diastolic dysfunction: reduced early diastolic flow velocity (VE: from 0.89 +/- 0.11 to 0.83 +/- 0.19 m/s; P < 0.01), reduced E/A ratio (1.7 +/- 0.4 to 1.2 +/- 0.4; P < 0.01), prolonged IVRT (72 +/- 12 to 114 +/- 12 ms; P < 0.01) and deceleration time (DT: to 189 +/- 17 to 227 +/- 18 ms; P < 0.01). Eight weeks after childbirth all parameters of left ventricular systolic and diastolic functions were normal., Conclusion: Preload alterations during normal pregnancy lead to reversible physiological left ventricular hypertrophy. Furthermore, we found a short-time reduction of systolic function just before childbirth and a significant alteration of the left ventricular diastolic filling pattern (abnormal relaxation pattern). While left ventricular systolic function was normal in all patients one week after childbirth, left ventricular hypertrophy and left ventricular diastolic dysfunction persisted for nearly two months.

Percutaneous transluminal coronary angioplasty (PTCA) of a native coronary artery via internal thoracic artery (ITA) graft after bypass surgery is a relatively rare procedure. Our current study evaluates the flow velocity patterns of the graft before and after PTCA. After intervention the mean diastolic flow velocity increased under rest and stress conditions. In addition, the graft patency was proved not before control angiography after 6 months. It could be verified that the measurement of flow velocity patterns under rest and stress conditions is a useful non-invasive procedure for monitoring long-term patency and PTCA-results of this vessel.

Continuous venovenous hemofiltration (CVVH) is the most widely used renal replacement therapy for the treatment of critically ill patients with acute renal failure on the intensive care unit. Whether or not congestive heart failure is an indication for CVVH is controversial and needs to be discussed. Therefore, we present a patient with congestive heart failure who was treated successfully with CVVH.

The report presents a transluminal angioplasty (PTCA) of a severe stenosis of the left anterior descending artery (LAD) behind the anastomosis; the internal thoracic artery (ITA) graft was used as a conduit. Before and after the PTCA the changing of velocity flow patterns under rest and stress conditions with a handgrip-maneuver were measured with a noninvasive transthoracic ultrasound Doppler system. The mean diastolic velocity, which represent coronary perfusion through the ITA graft, increased after successful PTCA at rest and under stress conditions. An additional increasing of the mean diastolic velocity at rest and under stress conditions was seen after six months before the catheterization proposing no signs of restenosis. For this reason the vessel could be classified prospectively patient. This could be confirmed during coronary angiography. We also present a review of the published reports concerning PTCA of ITA grafts and PTCA of the native vessel using the ITA as a conduit. In this review 286 cardiac interventions on 273 patients with a primary rate of success of 87% could be counted, the documented rate of restenosis was 30%, and the rate of complication was approximately 1%. The PTCA in ITA grafts or of the native vessel via ITA grafts, respectively, represent an alternative to reoperation. The ultrasound-duplex measurements are gaining an increasing significance for the noninvasive patency rate and post-interventional monitoring of the long-term PTCA result. With the augmentation of the ITA as a coronary bypass and expected increase of post-operative interventions, a noninvasive tool is necessary.

Objectives: This study investigated parameters of endogenous fibrinolysis, activation of coagulation and platelets, and endothelin levels before and after elective percutaneous transluminal coronary angioplasty (PTCA) in patients with stable coronary artery disease (CAD)., Background: Abrupt vessel closure is a serious short-term complication after PTCA and is often unforeseeable. Detailed insight into the effect of PTCA on hemostasis, platelets and the release of vasoconstrictive substances, which are among the mainly discussed mechanisms of abrupt vessel closure, is needed to enhance the safety of coronary intervention., Methods: Plasma levels of markers of platelet activity, coagulation, endogenous fibrinolysis and endothelins were determined in 20 patients with stable CAD undergoing elective PTCA. The blood specimens were drawn before, immediately after, 1 h after intervention and on the next morning., Results: All patients showed an initially uncomplicated PTCA. Regarding the efficacy of anticoagulation after receiving 15.000 IU heparin during PTCA, two groups were compared. In eight patients with ineffective anticoagulation production of thrombin and platelet activation directly after and 1 h after PTCA was significantly higher compared with 12 patients with effective anticoagulation. Despite the strong activation of coagulation, only a low fibrinolytic response could be observed. Endothelins rose significantly after PTCA in both groups but stayed longer on higher levels in patients with distinct thrombin generation. Three of the eight patients without sufficient heparin treatment suffered abrupt vessel closure., Conclusions: Initially uncomplicated dilation of coronary arteries leads to systemically measurable activation of coagulation and platelets in patients with ineffective doses of heparin and release of endothelins in all patients. Therefore, individual adjustment of anticoagulation and platelet inhibition in combination with effective antivasospastic substances are needed in every patient before, during and after initially uncomplicated PTCA to prevent this serious complication.

Introduction: The early determination of the myocardial manifestation is of considerable importance, since the prognosis of patients (P) with insulin dependent diabetes mellitus (IDDM) is generally masked by secondary cardiac complications. The aim of this study was to investigate whether young, asymptomatic P with IDDM and persisting normal systolic left ventricular (LV) function already show a diastolic LV dysfunction., Methods: An echocardiographical examination of 92 IDDM patients (age: 25 +/- 4 years) without known cardiac disease and of 50 control persons (C) of similar ages was carried out. P with a cardiac disease or long-term diabetic syndrome were excluded. Using M-mode echocardiography, morphological parameters and systolic time-intervals (fractional shortening; ejection fraction) were determined. Doppler indices were then measured: maximal early and late diastolic flow velocity (VE; VA), E/A ratio, acceleration and deceleration time (DT), isovolumetric relaxation time (IVRT)., Results: Although the left atrial and left ventricular dimensions, as well as the systolic functional parameters of all P with IDDM were normal, they showed a diastolic dysfunction with a reduction of the early diastolic filling (VE; 0.54 +/- 0.07 m/s vs 0.72 +/- 0.04 m/s; p < 0.01) and the E/A ratio (0.9 +/- 0.15 vs 1.99 +/- 0.22; p < 0.01), an increase in the atrial filling (VA; 0.76 +/- 0.05 m/s vs 0.39 +/- 0.04 m/s, p < 0.01), an extension of the IVRT (129 +/- 23 ms vs 78 +/- 6 ms, p < 0.01), and an increased DT (248 +/- 27 ms vs 188 +/- 8 ms, p < 0.01)., Conclusion: Even young P with IDDM, with a normal systolic ventricular function, suffer a diastolic dysfunction which serves as a marker of a diabetic cardiomyopathy. Therefore, echocardiography with measurements of systolic and diastolic functional parameters appears to be a sensible method for evaluating the course of diabetic cardiomyopathy.

Antiischemic effectiveness of long-term urokinase therapy and isovolemic hemodilution therapy has been reported in patients with symptomatic coronary artery disease, but both interventions have never been compared. In patients with refractory angina pectoris and end-stage coronary artery disease (clinical functional class III), isovolemic hemodilution (n = 9) (hydroxyethyl starch solution 6%, 1-2 times/week), and urokinase therapy (n = 11) (500,000 U urokinase per i.v. injection, 3 times a week) were performed over a period of 12 weeks, each additionally to maximal conventional treatment. Apart from the assessment of clinical symptoms and rheologic parameters, invasive hemodynamic measurements were carried out at rest and during exercise testing before and after treatment. After treatment with urokinase, patients showed a significant reduction of clinical symptoms (from 19.8 +/- 6.5 to 5.0 +/- 4.3 anginal events/week, p < 0.001), fibrinogen (from 410 +/- 88 to 238 +/- 40 mg/dl, p < 0.001), plasma viscosity (from 1.45 +/- 0.10 to 1.33 +/- 0.03 mPa x s-1, p < 0.01), and no changes of hematocrit (from 0.45 +/- 0.02 to 0.45 +/- 0.02) and whole blood viscosity (from 4.7 +/- 0.5 to 4.4 +/- 0.7 mPa x s-1); however, hemodilution resulted in a decrease of hematocrit (from 0.46 +/- 0.01 to 0.39 +/- 0.01, p < 0.001) and whole blood viscosity (from 4.7 +/- 0.5 to 4.0 +/- 0.3 mPa x s-1, p < 0.001) and no changes of initially comparable levels of clinical symptoms, fibrinogen, and plasma viscosity. Hemodynamic parameters at rest improved after urokinase therapy with a reduction of pulmonary capillary wedge pressure (from 9.1 +/- 5.1 to 5.5 +/- 2.8 mmHg, p < 0.05) at comparable levels of systemic vascular resistance (from 1510 +/- 340 to 1420 +/- 510 dyn x s x cm-5). Hemodilution did not result in any significant hemodynamic changes. Apart from clinical symptoms, long-term intermittent urokinase therapy reduces pulmonary capillary wedge pressure at rest. This may reflect an improved diastolic function due to a rheological enhancement of myocardial perfusion at the level of the coronary microcirculation. Isovolemic hemodilution seems to be of no benefit.

History and Clinical Findings: A 55-year-old female patient reported left-sided chest pain at rest as well as during exercise, which recurred during the last three years before admission. Cardiovascular risk factors included hypercholesterolemia and smoking. The physical examination of the patient was unremarkable., Investigations: The ECG at rest showed T-wave inversions in leads I, aVL, V3-V6 and ergometric exercise testing resulted in angina pectoris and descending ST-segments in leads V3-V6. Stress thallium 201 scintigraphy demonstrated a reversible perfusion deficit of the the anterior wall at peak exercise. The left ventricular angiogram and echocardiogram revealed normal end-diastolic dimensions and regular systolic contractions without signs of left ventricular hypertrophy. Selective coronary arteriography excluded hemodynamically relevant stenosis of the coronary arteries. A coronary artery fistula originating from a large, ectatic first diagonal branch with drainage into the left ventricle was observed., Treatment and Course: Because the patient rejected interventional therapy she was treated conservatively and follow-up investigations 3 and 4 years after arteriography revealed unchanged clinical symptomatology., Conclusion: In this case a "coronary steal" phenomenon caused by the coronary fistula induced myocardial ischemia. Therefore if present congenital coronary anomalies have to be considered in patients with chest pain and normal coronary angiogram.

Objective: To investigate in patients with arterial hypertension (HT) the extent of left ventricular (LV) hypertrophy and diastolic function in relation to atrial arrhythmias., Patients and Methods: In 112 hypertensive patients (40 women, 72 men; mean age 50 +/- 6.6 years) with a mean systolic blood pressure for the cohort of 170 +/- 5 mmHg, their first invasive coronary angiography was performed between July 1995 and October 1997 because of angina pectoris and/or an abnormal stress electrocardiogram. After excluding coronary heart disease LV dimensions and diastolic function were measured by echocardiography; in 59 of the 112 patients LV hypertrophy was demonstrated. In addition, long-term blood pressure monitoring, exercise and long-term electrocardiography, late-potential analysis and measurement of heart rate variability were undertaken. The control group consisted of 51 patients without arterial hypertension after exclusion of coronary heart disease., Results: Even in the hypertensive patients without LV hypertrophy diastolic LV function and ergometric exercise capacity were reduced. The risk of LV arrhythmias was significantly higher in patients with LV hypertrophy than those without and in the control group, as measured by the complexity of atrial arrhythmias (P < 0.001), the incidence of abnormal late potentials (P < 0.001) and reduction in heart rate variability (29.3 +/- 5.3 ms vs 47.8 +/- 12.1 ms vs 60.7 +/- 6.6 ms; P < 0.001). There were similar results regarding severe complex atrial arrhythmias (38.5 vs 15.0 vs 0%; P < 0.001). The incidence of atrial arrhythmias correlated with the LV diameter (r = 0.68, P < 0.001), LV morphological dimensions and diastolic function (isovolumetric relaxation time r = 0.44, P < 0.001) and the ratio of early to late diastolic inflow (r = 0.46; P < 0.001)., Conclusions: Hypertensive patients have a higher risk of atrial and ventricular arrhythmias, depending on the degree of LV hypertrophy. But atrial arrhythmias, in contrary to ventricular arrhythmias, are also closely related to abnormalities in LV diastolic function.

Antithrombotic therapy is a basic part in the treatment of acute as well as chronic coronary syndromes. The rationale is an enhanced platelet activity with predomination of procoagulatory mechanisms in coronary artery disease. The current status of antiplatelet drugs, anticoagulation, and chronic thrombolysis used in the treatment of chronic coronary syndromes is discussed. It is concluded that low-dose aspirin is the current drug of choice for long term oral treatment in patients with stable chronic coronary artery disease. In contrast, oral anticoagulation with coumadin should be considered in patients with higher risk for atrial or ventricular thrombosis. The impact of long-term intermittent urokinase therapy in patients with end-stage coronary artery disease and refractory angina pectoris leads to a marked improvement of clinical symptoms. Oral blockade of platelet membrane glycoprotein IIb/IIIa receptor and clinical trials regarding antiischemic effects of low-molecular weight heparins in chronic coronary syndromes are expected for the future.

During the last 25 years the internal thoracic artery has become a well established conduit for coronary revascularization. Next to angiography, duplex-sonography is increasingly used as a non-invasive imaging procedure for the evaluation of this graft vessel. Preoperative investigation in 117 patients has yielded a high level of agreement between angiography and duplex-sonography. While the preoperative flow-pattern is dominated by systolic flow as it is typical for vessels supplying skeletal muscle, the postoperative findings show an adaptation to the coronary vascular bed as the diastolic flow increases. These non-invasive measurements are well matched with invasive intravascular recordings. Coronary angiography and duplex-sonography of the internal thoracic artery yielded comparable findings in respect to the procedural result. Considering the increasing use of the internal thoracic artery in coronary artery bypass surgery, this non-invasive method should gain increasing relevance.

Patients with refractory angina pectoris and end-stage coronary artery disease represent an increasing clinical problem. Numbers of these patients will increase in the future for improved survival due to effective secondary prevention of coronary artery disease. Next to the evaluation of clinical symptoms non-invasive objective parameters of myocardial ischemia are of major relevance before initiation of alternative treatment modalities and for verification of antiischemic effectiveness. Based on our own experience it can be shown that in these patients testing which is mainly based on the patients physical exercise capacity is only of limited value due to the early occurrence of clinical symptoms. Furthermore diffuse perfusion abnormalities reduce the sensitivity of electrocardiographic and scintigraphic detection of ischemic changes. In contrast indirect measures of ischemia relating to the systolic or diastolic function of the left ventricle like doppler-echocardiography and radionuclide ventriculography seem to be promising approaches. This is confirmed by the results from the application of long-term intermittent urokinase therapy. Long-term intermittent urokinase therapy leads to an absolute enhancement of myocardial perfusion, which makes this approach superior to other medical interventions which are mainly based on a reduction of cardiac work-load.

Despite progress in the invasive revascularization procedures and even though conventional antianginal treatment has improved the quality of life in patients with symptomatic coronary artery disease considerably, an increasing number of patients suffers from end-stage coronary artery disease and refractory angina pectoris. For these refractory patients long-term intermittent urokinase therapy was developed as an antithrombotic intervention, which is based on its capacity to enhance thrombolysis and blood rheology, and may possibly lead to plaque regression. The coronary syndrome of refractory angina pectoris is characterized by a mismatch of severe coronary insufficiency and a relatively large amount of viable myocardium as indicated by an only moderately impaired left ventricular function. Prior to initiation of long-term intermittent urokinase therapy all potential measures to improve myocardial perfusion have to be considered in each patient. These supportive measures include rigorous reduction of LDL-cholesterol, which has proven antiischemic properties due to an improved endothelial function of epicardial conductance vessels possibly resulting in an antianginal effect. Apart from the proven antiischemic properties of long-term intermittent urokinase therapy in patients with refractory angina pectoris, objective signs of ischemic myocardial heart failure improve. Follow-up studies demonstrated a significant increase of left ventricular ejection fraction as evaluated with multi-gated blood pool analysis. Furthermore, left ventricular diastolic function normalized after a treatment period of 12 weeks. As the clinical effects last well beyond the actual treatment period and as they are accompanied by a remarkable increase in the quality of life, a complex approach as this one is justified in this highly symptomatic patient group.

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.

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.

The aim of the study was to evaluate whether a causal antiischemic intervention as percutaneous transluminal coronary angioplasty (PTCA) leads to a reduction of ventricular late potentials in the chronic post myocardial infarction period. In 24 patients, signal-averaged electrocardiograms (SAECG) for two groups were recorded for the analysis of ventricular late potentials (LP) before and after 6.0+/-4.2 months (group A, with PTCA) and 6.2+/-5.2 months, respectively (group B, conservative therapy). All patients presented prior myocardial infarction. LP were defined present if two of the three time domain criteria were met. In the whole study group, LP were positive in 73%. In group A, a PTCA was performed one month after the initial SAECG measurement. In group A, the presence of ventricular late potentials was significantly reduced (64% vs. 18%), whereas in group B only a slight decline of late potentials could be observed (85% vs. 62%). The parameters of the signal averaged ECG varied significantly in group A before and after PTCA (QRS 113.04+/-13.65 vs. 100.55+/-6.97 ms (p<0.05), RMS 24.04+/-24.13 vs. 35.39+/-16.89 muV (p=n.s.), LAS 41.23+/-13.27 vs. 29.68+/-6.47 ms (p<0.05)). The results in group B were not altered significantly.In conclusion, these results show that a PTCA of the infarct-related artery can lead to a reduction in ventricular late potentials in patients with significant coronary artery disease, who are also in the chronic post myocardial infarction period. Whether it is possible to improve the prognosis of these patients has also to be shown in future studies.

Objective: As pseudoaneurysm of the femoral artery after catheter introduction is a frequent complication, its causes and therapeutic options were investigated in a large patient collective., Patients and Methods: In a prospective study with colour-Doppler duplex sonography of 6928 patients after diagnostic and of 3764 after interventional cardiac catheterisation, pseudoaneurysms were diagnosed in 80 patients (0.75%), 46 after diagnostic (0.66%) and 34 after interventional (0.9%) catheterisation., Results: The incidence was higher in women than men (1.33% vs 0.58%; P < 0.05). Anticoagulation after sheath removal was the leading risk factor (n = 55, 68.8%), especially after interventional coronary intervention 85.3 vs 56.5%, P < 0.05). Local compression under duplex sonography monitoring was undertaken in 69 patients (86.3%), achieving aneurysmal obliteration in 53 (76.8%). Spontaneous thrombosis occurred in 15 of the remaining 27 patients, and surgical closure became necessary in 12., Conclusions: These data indicate a risk profile for the occurrence of pseudoaneurysm after cardiac catheterisation which can be dealt with by preventive measures. Local compression under duplex sonographic monitoring was the treatment of choice with a high success rate and low incidence of complications.

Background: Diabetic patients undergoing renal replacement therapy have a high cardiovascular mortality. As the rate of patients with diabetic nephropathy rises, adequate risk stratification subsequent to renal transplantation is warranted. It was the aim of our study to elucidate whether conventional risk factors are valid predictors of coronary artery disease in this group of patients with chronic renal failure subsequent to transplantation., Methods and Results: Between 1989 and 1993, 105 consecutive diabetic patients (70 men, 35 women, 77 type I and 28 type II diabetics, mean age 43 +/- 12 years) were examined during the first six months of dialysis treatment. Coronary angiography was performed in all patients regardless of clinical symptoms of coronary artery disease (CAD). In 38 patients (36%) CAD was documented (single-vessel disease: 17 patients, double-vessel disease: 6 patients, triple-vessel disease: 15 patients). Manifestations of coronary atherosclerosis were seen in 49 patients (47%). Angina pectoris was present in 9 out of 38 patients (24%), the sensitivity to detect CAD was 43% and 52% for ST-segment depression assessed at rest. Risk factors for atherosclerosis like hypertension, smoking, cholesterol (total cholesterol, HDL-,LDL-cholesterol), triglycerides as well as concentrations of lipoprotein (a) and fibrinogen were not significantly different in patients with or without coronary artery disease. Atherosclerotic manifestations of cerebral and peripheral arteries as well as manifestations of diabetic microangiopathy like retinopathy did not correlate with the prevalence of CAD. In 11 out of 38 patients (29%) cardiac interventions (3 x CA BG, 8 x PTCA) were performed. All of them were defined as transplantable after myocardial revascularisation., Conclusions: Clinical symptoms as well as the cardiovascular risk profile are not valid predictors of CAD in diabetic patients with chronic renal failure. Therefore coronary angiography should be performed in all diabetic patients prior to renal transplantation.

Patients with end-stage renal disease (ESRD) have a high incidence of coronary artery disease. In 30-60% of these patients coronary artery disease can be demonstrated by coronary angiography often prompting myocardial revascularization. Previous studies on PTCA in patients with ESRD have suggested a high rate of procedural complications and restenosis. We studied the rate of restenosis after PTCA in 23 patients with chronic renal failure (17 males, 6 females, age: 52.5 +/- 18.3 years). After primarily successful PTCA all patients were restudied angiographically within 6-12 months. Using quantitative coronary angiography 13 patients (56%) demonstrated restenosis (stenosis > 50% luminal diameter). In 11 of these patients further revascularization therapy was indicated (6 x PTCA, 5 x CABG). Before follow-up angiography 12 patients demonstrated recurrence of angina pectoris, the sensitivity of clinical symptoms for angiographic restenosis was 69%. High concentrations of triglycerides (265 +/- 160 mg/dl), total cholesterol (258 +/- 53 mg/dl) with low HDL-levels (34 +/- 14 mg/dl) as well as elevated plasma levels of fibrinogen (481 +/- 114 mg/dl) were measured before PTCA. The mechanisms contributing to the high rate of coronary restenosis in patients with ESRD remain unclear, influence of lipid abnormalities, hemostatic factors and fibrinolytic state as well as primarily uremic factors have to be discussed. Prospective interventional studies are needed to address the relevance of PTCA for myocardial revascularization in this patient group.

Elevated fibrinogen levels as well as an impaired activity of the fibrinolytic system are regarded as important cardiovascular risk factors. To elucidate a potential interrelation between fibrinogen as an indicator of a hypercoagulable state and the endogenous fibrinolytic function hemostatic and rheological as well as lipid parameters were determined in 224 consecutive patients, who underwent elective coronary angiography. In the selected study population of 81 men and 19 women with fibrinogen concentration either > or = 3.5 g/l (n = 70) or < or = 2.5 g/l (n = 30) hyperfibrinogenemia was found to be significantly associated with increased concentrations of plasmin-alpha 2-antiplasmin complex [PAP [median (25.-75. percentile)], 534 (361-680) micrograms/l vs. 289 (243-440) micrograms/l; p < 0.001] and tissue plasminogen activator (t-PA) antigen [9 (6-11) micrograms/l vs 8 (5-9) micrograms/l; p < 0.05] while this association was lost in the subgroup of patients with angiographically normal coronary arteries (n = 26). In addition to these findings fibrinogen was significantly correlated with PAP (r = 0.40, p < 0.001; n = 224) and t-PA antigen (r = 0.2, p < 0.01; n = 224) after adjustment for age, diabetes mellitus, lipid parameters and leucocyte counts. It can be argued that elevated fibrinogen levels in patients with coronary artery disease are concomitant with an activation of the fibrinolytic system.

We analyzed the incidence and management of major vascular complications at the arterial puncture site following diagnostic or interventional cardiac catheterization. 27387 cardiac catheterization procedures were performed for diagnostic (n = 19581) or interventional (n = 7806) purposes at our institution during a 7-year study period. A total number of 114 major vascular complications (0.42%) were identified. In 36 (0.13%) patients an arterial occlusion at the puncture site was detected, 34 patients (0.12%) had severe hematoma (blood transfusion or surgical repair necessary), 32 patients (0.12%) developed false aneurysms, 9 patients (0.03%) with av-fistulas and 3 patients (0.01%) had other complications. The following factors were predictive for a significant increase in the incidence of major vascular complications: Female gender, interventional catheterization using larger introducer sheaths and necessitating effective perioperative doses of heparine, and peripheral vascular disease. Operative repair was necessary in 62 patients (54%), 34 patients (30%) were treated conservatively. In 18 patients (17%) acute vascular occlusion could be managed by percutaneous transluminal balloon dilatation and intravascular thrombolysis of the obstruction, in 3 patients additional stent-implantation was necessary in the presence of a large occlusive dissection. Overall the rate of clinically significant major vascular complications is low. In the future a greater number of vascular complications at the entry site for cardiac catheterization will be treated with nonoperative methods (e.g. manual compression of pseudoaneurysms or catheter-based techniques for recanalization of acutely occluded vessels.

Under normal conditions the coronary system of the human heart is not hermetically isolated from the surrounding structures nor the ventricles, but is in various ways connected to the adjacent arteries and the cardiac chambers. These natural connections have been models for most surgical efforts to revascularize the myocardium. Numerous anastomoses between the aorta and the coronary branches functionally resemble aorto-coronary bypass grafts. Coronaro-ventricular anastomoses do also exist in the myocardium and therefore transmyocardial laser revascularization should allow blood to penetrate from the ventricle into the myocardium. This process should not be called "reptilization" of the human heart, as in large reptilian hearts the nutrition of an extensive amount of myocardium only by diffusion is highly unlikely. Transmyocardial laser revascularization results in a relevant reduction of clinical symptoms and an increase of exercise capacity in approximately two thirds of the patients treated. Objective data of enhanced myocardial perfusion as assessed by positron emission tomography and stress echocardiography has up to now only been presented by smaller studies. Open laser channels are rarely visualized by conventional ventriculography for the limited resolution of the technique. Possibly contrast-echocardiography may offer a more appropriate option to proof the systolic filling of the laser channels, as recently reported in patients. This would allow a correlation between clinically successful revascularization and functioning channels in contrast to an early or late failure due to the closure of the channels. As to the current opinion, transmyocardial laser revascularization is no alternative to established medical, interventional or surgical therapies but may in conjunction with bypass surgery or as a sole procedure offer a new option for those patients, who were recently considered to be refractory to conventional treatment. Experimental studies in particular should contribute to the understanding of therapeutic mechanisms and lead to standardized indications in the surgical treatment of end-stage coronary heart disease. Even though in transmyocardial laser revascularization the perioperative risk depends mainly on the degree of cardiac disease and the overall state of the patient, and impaired left ventricular function is per se no exclusion criterium, if viable myocardium is detectable. Many questions concerning indications, long-term prognosis and pathophysiological mechanisms are still open to discussion and have to be answered in order to find standardized applications for treatment of end-stage coronary artery disease.

Long-term intermittent urokinase therapy has been developed for patients with severe coronary artery disease and refractory angina pectoris. This therapeutic approach is predominantly effective at the microcirculatory level based on a combination of rheologic and fibrinolytic effects; furthermore, plaque regression seems to be a possible mechanism. Patients with refractory angina pectoris are characterized by severe coronary artery disease without a therapeutic option for conventional revascularization procedures, only slight impairment of left ventricular systolic function and hyperfibrinogenemia, which results in further enhancement of myocardial ischemia due to microcirculatory impairment of blood flow. In this article data on the anti-ischemic effectiveness as well as first results on the impact of this therapeutic approach on hemodynamics are described. A dose-response study, which compared 3 x 50,000 IU with 3 x 500,000 IU urokinase three times a week over a treatment period of 12 weeks demonstrated subjective as well as objective antiischemic effectiveness. Only patients who were treated with 500,000 IU per injection achieved marked increases in exercise capacity, while some patients in the low-dose group presented even with a deterioration of exercise performance. First hemodynamic studies could not show marked changes of systolic parameters, either at rest or during exercise. But a decrease of pulmonary capillary wedge pressure at rest after treatment with 500,000 IU per injection indicates an improvement of diastolic function as a result of enhanced myocardial perfusion. Echocardiographic measurements of transmitral Doppler flow in 21 patients with end-stage coronary artery disease demonstrated normalization of early and late diastolic filling rates in most cases. These changes were accompanied by a reduction of clinical signs of heart failure. Long-term intermittent urokinase therapy is a valuable approach as it not only improves quality of life during the actual treatment period but by the persistence of therapeutic effects following the cessation of therapy.

Interventions that modify lipid metabolism and blood coagulation have been shown to favourably influence the natural course of coronary artery disease in terms of the primary prevention and treatment of acute cardiovascular events. Various findings suggest that such interventions may also preserve and enhance myocardial perfusion in the chronic stage of the disease. Long-term intermittent urokinase therapy was developed for patients with end-stage coronary artery disease and refractory angina pectoris. A dose of 500,000 IU of urokinase given intravenously as a bolus three times a week for of 12 weeks reduced symptoms by 70% and was accompanied by objective improvements in myocardial perfusion and an increase of ergometric exercise capacity. The possible therapeutic mechanisms of long-term intermittent urokinase therapy-improvement of rheological blood properties mediated by fibrinogen reduction, thrombolysis of non-occlusive subclinical thrombi, and regression of atherosclerotic plaques-are discussed in the context of other antithrombotic approaches.

The most important function of the coronary vasculature is the effective regulation of coronary blood flow according to the metabolic needs of the myocardium. Under physiological conditions, coronary blood flow is regulated by a balance of vasoconstricting and -dilating components which can be differentiated with regard to the site (macro- vs. microcirculation), compartment (endothelium vs. vascular smooth muscle), and mechanism of action (receptor dependent vs. independent). This balance includes on the one hand the ability of the coronary circulation to maintain a relatively constant blood flow at any given oxygen demand irrespective of perfusion pressure (coronary autoregulation). On the other hand, coronary blood flow can be increased rapidly and effectively several-fold when myocardial oxygen demand increases. Previous investigations have demonstrated that the coronary endothelium plays a key role in the development of arteriosclerotic vascular lesions. In the time course of arteriosclerosis, functional alterations in endothelium dependent vasodilatation alterations are already present before angiographically demonstrable morphologic lesions. In the present manuscript, the diagnostic methods used to assess clinically the coronary macro- and microcirculation with regard to endothelium and smooth muscle dependent vasomotion are reviewed. In addition, present pharmacotherapeutic strategies to improve myocardial perfusion in coronary artery disease are discussed.

Symptomatic end-stage arterial disease in coronary artery or peripheral arterial occlusive disease represents an increasing clinical problem as cardiovascular mortality in these patient groups has declined due to improved secondary prevention. While in peripheral arterial occlusive disease amputation with subsequent life-long physical disability is the major problem, patients with end-stage coronary artery disease and refractory angina pectoris repeatedly report to the emergency ward with the clinical symptoms of unstable coronary syndromes, but myocardial infarction is generally ruled out. For these patients long-term intermittent urokinase therapy has been developed as an alternative treatment modality. Potential mechanisms for clinical effectiveness include improvement of rheological blood properties, thrombolysis of non-occluding arterial thrombi and possibly plaque regression. In coronary artery disease urokinase is applied as an intravenous bolus injection of 500,000 IU urokinase three times a week over a period of 12 weeks. This leads to a marked reduction of fibrinogen by about 35% and of clinical symptoms by around 70% accompanied by a reduction of exercise-induced myocardial ischemia. In observational studies in patients with peripheral arterial occlusive disease injections of 500,000 IU of urokinase were usually given daily for a shorter time period of three to four weeks with a clinical success rate, defined as a cessation or marked reduction of rest pain and/or salvage of a limb, of around 50%. Given the state of critical ischemia in both entities of atherosclerotic disease, long-term intermittent urokinase therapy represents a promising antiischemic approach. In particular in patients with peripheral arterial occlusive disease randomized controlled trials with prolonged treatment periods, which are likely to improve clinical results, are warranted.

Apart from the relevance of disorders of lipid metabolism for the clinical and morphological progression of coronary artery disease, coronary thrombosis has received increasing attention in recent years. It is undoubtedly the decisive factor in the pathogenesis of acute coronary syndromes, which is underlined by the therapeutic success of various antithrombotic interventions. Furthermore coronary thrombosis is regarded to be a key factor for morphological disease progression also in stable coronary syndromes, which eventually may lead to critical limitation of myocardial perfusion. This is caused by the formation of subclinical coronary thrombi, which either undergo endogenous lysis or become morphologically fixed as they are incorporated into the plaque. Besides local factors, systemic disturbances of hemostasis and endogenous thrombolysis are of relevance. The concept of thrombotic progression of coronary thrombosis is supported by data on the reduction of morphological disease progression or antiischemic effectiveness of anti-thrombotic interventions like aspirin, low-molecular weight heparin and low-dose intermittent urokinase therapy. Percutaneous transluminal coronary angioplasty results in deep mechanical injury of the vessel wall, which is accompanied by secondary coronary thrombosis in the majority of the cases, not necessarily leading to abrupt vessel closure. Particularly, dilatation of primary thrombus as it has been described as the substrate of the culprit lesion in unstable coronary syndromes, promotes release of thrombin and activation of platelets, which in turn furthers the proliferative processes in the pathogenesis of restenosis. Even though data on the reduction of the rate of restenosis by the use of platelet aggregation inhibitors like aspirin, ticlopidin and dipyridamole have not consistently supported this concept, the EPIC. Study has shown that even in patients with stable angina pectoris clinical restenosis rate may be reduced by a platelet-IIb/IIIa-antagonist.

Endothelin (ET), the most potent endogenous vasoconstrictor with mitogenic potency, is generated from its precursor big-endothelin (BET) in a proteolytic process and discussed as a pathogenetic factor in coronary artery disease and in the acute coronary syndromes. Several studies documented elevated plasma endothelin concentrations in acute myocardial infarction, but conflicting results were reported in patients with stable and unstable angina. Only few studies determined big endothelin, although it half-life and plasma concentrations are higher in comparison to endothelin. ET and BET levels (Radioimmunoassay, Biomedica GmbH, Vienna) were determined in patients with stable angina (SAP, n = 20), unstable angina (IAP, n = 12), acute myocardial infarction (AMI, n = 12) and healthy subjects (NP, n = 11). The concentrations of ET and BET (median (minimum-maximum) in fmol/ml) of the patients with stable angina (SAP: ET 0.7 (0.3-1.1); BET 1.7 (0.7-2.9)), unstable angina (IAP: ET 1.0(0.5-1.7); BET 2.5 (1.3-4.1)) and acute myocardial infarction (AMI: ET 1.2 (0.6-2.3); BET 3.6 (3.2-5.3)) showed a significant difference compared to controls (NP: ET 0.5 (0.4-0.7); BET 1.4 (1.1-1.7)) (SAP vs. NP: ET p < 0.01; BET p < 0.05; IAP and AMI vs. NP: ET and BET p < 0.001). Also, the concentrations of the peptides differed significantly dependent on the clinical severity of coronary artery disease (AMI vs. SAP: ET and BET p < 0.001; AMI vs. IAP: BET p < 0.05; IAP vs. SAP: ET p < 0.05; BET p < 0.01). Twelve of 15 patients with big endothelin concentrations over 3 fmol/ml suffered acute myocardial infarction. Seven of 12 patients with AMI showed elevated ET and BET concentrations before the increase of creatinecinase. There was no correlation between number of risk factors per patient, cholesterin and subfractions, severity of CAD classified in one-two-three-vessel disease or coronary score according to modified criteria of the American Heart Association (AHA). We conclude that in patients with coronary artery disease endothelin and big endothelin levels are elevated and related to the clinical and not to the morphological severity of coronary artery disease. Big endothelin is the more sensitive parameter in comparison to endothelin and indicates a severe course of myocardial ischemia in patients with unstable angina. The development of assays with the possibility of a quick determination of the peptides may be valuable for risk stratification of acute coronary events.