[Anticoagulant and thrombolytic agents in acute coronary syndromes]. / Antithrombotische und thrombolytische. Therapie beim akuten Koronarsyndrom.

The term acute coronary syndrome (ACS) pertains to the instable and life-threatening forms of a clinically manifest coronary artery disease with biochemical and/or electro-cardiographic evidence of myocyte cell death. In detail, it includes the unstable angina pectoris, the non-ST segment elevation myocardial infarction (NSTEMI) the ST segment elevation myocardial infarction (STEMI) and as well the sudden cardiac death. As early reperfusion of ischaemic myocardium is the most effective way for limiting infarct size by restoring the balance between myocardial oxygen supply and demand, it is the most important therapeutic goal to achieve early and complete antegrade flow in the occluded or restricted vessel, related with a reduction of short and longtime complications as heart failure and severe arrhythmias. It is generally accepted, that the primary percutaneous coronary intervention (PCI) is the method of choice in acute myocardial infarction (STEMI) to restore TIMI-3 blood flow in occluded coronary arteries, if this can be performed within two hours of symptom onset and by a highly specialized team. Since these requirements are only met in 20% of hospitals caring for patients with STEMI in Germany, the therapy with thrombolytic and anticoagulant agents plays still an important role. Apart from a rapid and effective prehospital primary care, it depends furthermore on a differentiated anticoagulatory and antithrombotic therapy during coronary intervention to get optimal results.

[Anticoagulant and thrombolytic agents in acute coronary syndrome]. / Antikoagulanzien und Thrombolytika beim akuten Koronarsyndrom.

The term acute coronary syndrome (ACS) pertains to the instable and life-threatening forms of a clinically manifest coronary artery disease with biochemical and/or electrocardiographic evidence od myocyte cell death. In detail, it includes the unstable angina pectoris, the non-ST segment elevation myocardial infarction (NSTEMI) the ST segment elevation myocardial infarction (STEMI) and as well the sudden cardiac death. As early reperfusion of ischaemic myocardium is the most effective way for limiting infarct size by restoring the balance between myocardial oxygen supply and demand, it is the most important therapeutic goal to achieve early and complete antegrade flow in the occluded or restricted vessel, related with a reduction of short and longtime complications as heart failure and severe arrhythmias. It is generally accepted, that the primary percutaneous coronary intervention (PCI) is the method of choice in acute myocardial infarction (STEMI) to restore TIMI-3 blood flow in occluded coronary arteries, if this can be performed within two hours of symptom onset and by a highly specialized team. Since this requirements are only met in 20% of hospitals caring for patients with STEMI in Germany, the therapy with thrombolytic and anticoagulant agents plays still an important role. Apart from a rapid and effective prehospital primary care, it depends furthermore on a differentiated anticoagulatory and antithrombotic therapy during coronary intervention to get optimal results.

[Assessment of left ventricular function and volume by myocardial perfusion scintigraphy--comparison of two algorithms]. / Myokardperfusionsszintigraphie zur Bestimmung der linksventrikulären Funktion und Herzvolumina--zwei Auswerteverfahren im Vergleich.

AIM: Left ventricular volume and function can be computed from gated SPECT myocardial perfusion imaging using Emory Cardiac Toolbox (ECT) or Gated SPECT Quantification (GS-Quant). The aim of this study was to compare both programs with respect to their practical application, stability and precision on heart-models as well as in clinical use. METHODS: The volumes of five cardiac models were calculated by ECT and GS-Quant. 48 patients (13 female, 35 male) underwent a one day stress-rest protocol and gated SPECT. From these 96 gated SPECT images, left ventricular ejection fraction (LVEF), end-diastolic volume (EDV) and end-systolic volume (ESV) were estimated by ECT and GS-Quant. For 42 patients LVEF was also determined by echocardiography. RESULTS: For the cardiac models the computed volumes showed high correlation with the model-volumes as well as high correlation between ECT and GS-Quant (r > or = 0.99). Both programs underestimated the volume by approximately 20-30% independent of the ventricle-size. Calculating LVEF, EDV and ESV, GS-Quant and ECT correlated well to each other and to the LVEF estimated by echocardiography (r > or = 0.86). LVEF values determined with ECT were about 10% higher than values determined with GS-Quant or echocardiography. The incorrect surfaces calculated by the automatic algorithm of GS-Quant for three examinations could not be corrected manually. 34 of the ECT studies were optimized by the operator. CONCLUSION: GS-Quant and ECT are two reliable programs in estimating LVEF. Both seem to underestimate the cardiac volume. In practical application GS-Quant was faster and easier to use. ECT allows the user to define the contour of the ventricle and thus is less susceptible to artifacts.

Evaluation of transmyocardial laser revascularization by following objective parameters of perfusion and ventricular function.

BACKGROUND: Does transmyocardial laser revascularization (TMLR), a new surgical technique for treating patients with otherwise intractable angina pectoris, improve myocardial perfusion, metabolism, and, consequently, function? METHODS: Patients referred for TMLR, alone or with coronary artery bypass grafting (CABG), were preoperatively evaluated clinically and by treadmill stress testing, echocardiography, ventriculography, radionuclide assessment of perfusion and metabolism, and hemodynamic assessment. Intraoperatively it was decided that some patients only required CABG. Follow-up evaluations were repeated after 6 (n = 40) and 12 months (n = 23) and compared with preoperative values. RESULTS: CABG only was performed in 35 cases, TMLR + CABG in 17, TMLR only in 45. 1-year mortality was 11% in the TMLR, zero in the TMLR + CABG, and 11% in the CABG groups. In all groups a significantly improved CCS angina- and NYHA class was observed immediately after operation and after 6 and 12 months. In all study groups treadmill tolerance (p<0.05) improved, but regional and global function, perfusion at rest, and metabolism were not significantly changed at 6 and 12-months follow-ups. Perfusion studies under stress demonstrated an improvement only in the CABG group after 12 months (p<0.05), whereas in both TMLR groups the lasered ischemic segments remained unchanged. CONCLUSIONS: TMLR significantly improves long-term clinical status and treadmill stress tolerance, but appears to have little if any effect upon regional and global function, perfusion, and metabolism.

[Non-invasive diagnostic procedures for heart failure: echocardiography, myocardial perfusion scintigraphy and radionuclide ventriculography]. / Nicht-invasive Untersuchungen zur Diagnose der Herzinsuffizienz: Echokardiographie, Myokardszintigraphie und Radionuklidventrikulographie.

Even though the diagnosis of heart failure can often be made at bedside from the patient's history and a thorough physical examination, some mechanical examinations are needed to objectify the clinical symptoms. Due to the chronic and progressive character of heart failure with repeated periods of clinical treatment, non-invasive and reproducible methods are of great importance. Thanks to technical progress in data-acquisition and -processing, echocardiography has become one of the most important diagnostic tools in clinical cardiology. Many questions associated with the diagnosis and treatment of heart failure can be answered with the aid of the wide spectrum of echocardiography, including morphological description in conventional M- or B-Mode and functional analysis based on Dopplertechnique. On the other hand well-established nuclear techniques like myocardial perfusion scintigraphy and radionuclide ventriculography profit from recent technical development. In addition, the modification, specification and standardisation of examination protocols improve the diagnostic reliability of nuclear medical techniques. Performed by a specialist, both principles of examination--ultrasound and scintigraphy--are valid in the diagnosis of heart failure and in therapy-management.

[Treatment strategies in therapy refractory angina pectoris: transmyocardial laser revascularization]. / Behandlungsstrategien bei therapierefraktärer Angina pectoris: Transmyokardiale Laserrevaskularisation.

BACKGROUND: Does transmyocardial laser revascularization (TMLR) as a new surgical technique for treating patients with otherwise intractable angina pectoris improve myocardial perfusion or contractility? METHODS: Sixty-seven patients transferred for TMLR were evaluated by clinical evaluation, treadmill stress testing, echocardiography, ventriculography, and hybrid positron emission tomography preoperatively and in patients treated with TMLR at 6 and 12 month follow up. Hemodynamic assessment and clinical evaluation were performed perioperatively. RESULTS: In 28/67 cases (42%) CABG, in 9/67 patients (13%) CABG in combination with TMLR (combined group), and in 30/67 patients (45%) only TMLR (sole group) were performed. Perioperative mortality in the sole group was 13%, in the combined group zero, and in the CABG group 11%. In all groups a significantly improved clinical status (p < or = 0.01) 1 week postoperatively and in TMLR groups also at 6 and 12 months was observed. In the TMLR groups treadmill tolerance (p < 0.05) improved, although function, perfusion, and metabolism did not change significantly at the 6 and 12 month follow up. CONCLUSION: TMLR significantly improves clinical status and treadmill stress tolerance, but does not change function, perfusion, and metabolism.

[Bypass perforation by stent implantation: complication management. A case report]. / Bypass-Perforation durch Stentimplantation: Komplikationsmanagement. Ein Fallbericht.

We describe a case-report on an perforation of an aorto-coronary venous bypass graft, a complication induced by a stent-implantation. Perforations of coronary arteries are rare, however, for interventional cardiologists well-known complications. This case report is of special interest (1) because the perforation did not occur in a coronary artery but rather in an eight year old venous bypass graft and (2) because the perforation was induced by a stent-implantation. In addition, this case report describes in great detail the management of vessel perforation: several invasive methods contributed to minimize pericardial effusion and to stabilize the patient until surgical revision could be performed.

Transmyocardial laser revascularization (TMLR) in patients with unstable angina and low ejection fraction.

OBJECTIVE: Does perioperative use of the intraaortic balloon pump (IABP) improve the postsurgical outcome of patients presenting with endstage coronary artery disease, unstable angina and low ejection fraction transferred for transmyocardial laser revascularization (TMLR)? METHODS: TMLR, as sole therapy combined with the perioperative use of an intraaortic balloon pump has been assessed in seven patients with endstage coronary artery disease, unstable angina and low ejection fraction (EF < 35%). Six out of seven patients had signs of congestive heart failure. These patients are compared with 23 patients with endstage coronary artery disease, stable angina and EF > 35%, who were treated with TMLR as sole therapy without the use of IABP. The creation of transmural channels was performed by a CO2-laser. All patients were evaluated by hybrid positron emission tomography (perfusion SPECT and viability PET) and ventriculography preoperatively. Echocardiography, clinical status and hemodynamic assessment by Swan Ganz catheter were performed perioperatively. RESULTS: The perioperative mortality of this combined procedure (TMLR and IABP) was zero. Three out of seven patients had pneumonia with complete recovery. Swan Ganz catheter examinations showed deterioration of LV-function after TMLR intraoperatively and improvement after 2 h and further after 6 h on ICU (P < 0.05). In contrast, a decrease of LV-function in sole TMLR patients with an EF > 35%) has not been observed. Patients with EF < 35% needed the IABP for 2.3 days and moderate dose catecholamines for a mean of 3.0 days. The postoperative EF and resting wall motion score index (WMSI) of all analysed LV segments (evaluated by echocardiography) did not change compared to baseline (EF 31.3+/-2.6 preop. to 32.8+/-3.2 postop.; WMSI: 1.75+/-0.14 at baseline to 1.71+/-0.17 postop.). The average Canadian Angina Class at the time of discharge decreased from 4.0+/-0 (baseline) to 2.3+/-0.5 (P < 0.05) and the NYHA-Index from 3.9+/-0.3 to 2.7+/-0.5. No patient had signs of angina pectoris, whereas two patients still had signs of congestive heart failure. CONCLUSIONS: The reported data support our concept to start IABP preoperatively in patients with reduced LV contractile reserve in order to provide cardiac support during the postoperative phase of reversible decline of LV-function induced by TMLR.

["Myxoma syndrome"--a "benign" disease with "malignant" course]. / "Myxoma-Syndrom"--eine "benigne" Erkrankung mit "malignem" Krankheitsverlauf.

We are reporting on a 36 year-old woman who presented with recurrent cardiac myxomas over a period of nine years. Two of the tumors typically originated in the left atrium and one in the right atrium. Tumor embolization was the presenting symptom twice, leading to reversible cerebral ischemia and minor pulmonary embolism, respectively. The third tumor remained asymptomatic and was detected during routine echocardiographic examination. Based on a positive family history of cardiac tumors, a facially pronounced hyperpigmentation of the skin and the presence of a thyroid adenoma, the diagnosis of a "myxoma syndrome" was established. Patients with "myxoma syndrome" are generally younger than their counterparts with "sporadic myxoma" (mean age at diagnosis 25 vs. 56 years) and have a high frequency of unusual skin freckling (68%). Familial clustering of cardiac myxomas is also frequent (25%). The tumors may be located in any of the cardiac chambers (87% in the atrias, 13% in the ventricles, 50% at multiple sites simultaneously) and have relatively high (18%) 5-year recurrence rate after surgical excision. Since the clinical signs of cardiac tumors are non-specific, diagnosis essentially relies on cardiac imaging by echocardiography, computer tomography, or angiography. The superiority of transesophageal echocardiography is emphasized in this report.

Coronary atherosclerotic wall thickening and vascular reactivity in humans. Elevated high-density lipoprotein levels ameliorate abnormal vasoconstriction in early atherosclerosis.

BACKGROUND: Abnormal vascular reactivity represents a fundamental disturbance in vascular biology with the development of atherosclerosis. Because endothelial vasodilator function plays a pivotal role in controlling vasomotor tone, we hypothesized that atherosclerotic wall thickening might directly interfere with deficient endothelium-mediated dilation and thereby contribute to the abnormal reactivity of atherosclerotic arteries in vivo. METHODS AND RESULTS: In 26 patients without focal stenoses in the left anterior descending coronary artery, acetylcholine (0.036 to 3.6 micrograms/mL) was infused into the artery to evaluate endothelium-mediated vasodilation. Segmental vasomotor responses to acetylcholine were correlated with the local extent of atherosclerotic wall thickening quantitated by intracoronary ultrasound examination. Seventeen of the patients also underwent cold pressor testing to assess the vasoreactivity to sympathetic activation. The response of coronary artery segments to acetylcholine varied from 35% dilation to 52% constriction and demonstrated a segmental pattern, with dilation and constriction observed in different segments of the same artery. The vasomotor response to acetylcholine was closely correlated with the extent of local atherosclerotic wall thickening (r = -.82, P < .0001). Over the entire range of atherosclerotic wall thickening, segments from patients with elevated high-density lipoprotein (HDL) cholesterol serum levels (> 75th percentile) demonstrated a significantly blunted constrictor response to acetylcholine (P < .01 at the maximal acetylcholine concentration) compared with segments from patients with HDL cholesterol < 75th percentile. The degree of constriction or dilation in response to the acetylcholine infusion correlated with the response to cold pressor testing (r = .75, P < .0001). Again, the cold pressor test-induced constrictor response was significantly (P < .05) blunted in segments from patients with elevated HDL cholesterol serum levels compared with those from patients with HDL cholesterol < 75th percentile despite equal degrees of atherosclerotic wall thickening. CONCLUSIONS: Coronary vasomotor responses to the endothelium-dependent dilator acetylcholine and to sympathetic stimulation by cold pressor test correlate with local atherosclerotic wall thickening. Thus, the degree of abnormal local vascular reactivity is closely related to the extent of atherosclerotic "plaque load" in human epicardial arteries in vivo. Elevated HDL cholesterol serum levels ameliorate abnormal vasoconstriction at any given extent of atherosclerotic wall thickening, suggesting that HDL cholesterol exerts a beneficial effect on abnormal vascular reactivity, a fundamental functional disturbance associated with coronary atherosclerosis.

Assessment of endothelial modulation of coronary vasomotor tone: insights into a fundamental functional disturbance in vascular biology of atherosclerosis.

The endothelium plays a major role in modulating vascular smooth muscle tone by synthesizing and metabolizing a number of vasoactive substances. Since the endothelium is both a target for and a mediator of vascular disease, functional alterations in coronary vascular reactivity due to endothelial dysfunction might play an important integral part in the clinical presentation of coronary artery disease. Recent advances in interventional techniques including intracoronary instrumentation by Doppler catheters to measure blood flow velocities and 2-D-ultrasound catheters to evaluate arterial wall architecture during coronary angiography provided the diagnostic tools to assess endothelial vasodilator function and its relation to atherosclerotic disease. The current weight of evidence suggests that disturbances of vasomotor function of epicardial conductance vessels are fundamental to the development of atherosclerosis, and impaired endothelial vasodilation is the predominant mechanism underlying inappropriate vasoconstriction in atherosclerosis. However, endothelial vasodilator dysfunction is not only confined to atherosclerotic epicardial vessels, but may also extend into the coronary microcirculation, which does not develop overt atherosclerotic lesions, but determines coronary blood flow in the absence of hemodynamically significant stenoses. The most important factors associated with impaired endothelium-mediated dilation of the coronary microcirculation are hypercholesterolemia and advanced age. With respect to the clinical presentation of coronary artery disease, endothelial vasodilator dysfunction appears to play a causative role for triggering myocardial ischemia in stable angina pectoris, to aggravate the sequelae of acute ischemic syndromes, and might be the primary underlying mechanism in some patients with syndrome X, whereas variant angina appears to be related to a hyperreactivity of the vascular smooth muscle layer. Thus, the assessment of endothelium-mediated modulation of coronary vasomotor tone in the clinical setting offers unique and important insights into mechanisms leading to ischemic manifestations of coronary artery disease.

Endothelium-mediated coronary blood flow modulation in humans. Effects of age, atherosclerosis, hypercholesterolemia, and hypertension.

The effects of age, atherosclerosis, hypertension, and hypercholesterolemia on vascular function of the coronary circulation were studied by subselective intracoronary infusions of acetylcholine, which releases endothelium-derived relaxing factor, and papaverine, which directly relaxes vascular smooth muscle, in normal patients (n = 18; no risk factors for coronary artery disease), in patients with evidence of early atherosclerosis but normal cholesterol levels and normal blood pressure (n = 12), in patients with hypertension without left ventricular hypertrophy (n = 12), and in patients with hypercholesterolemia (n = 20). Papaverine-induced maximal increases in coronary blood flow were significantly greater in normals, but no differences were noted between the groups of patients with early atherosclerosis, with hypertension, and with hypercholesterolemia. The capacity of the coronary system to increase blood flow in response to acetylcholine was similar in normal and normocholesterolemic patients with epicardial atherosclerosis and/or hypertension but was significantly impaired in patients with hypercholesterolemia, irrespective of evidence of epicardial atherosclerotic lesions. Age (r = -0.62, P < 0.0001) and total serum cholesterol levels (r = -0.70; P < 0.0001) were the only significant independent predictors of a blunted coronary blood flow response to acetylcholine. Thus, hypercholesterolemia and advanced age selectively impair endothelium-mediated relaxation of the coronary microvasculature in response to acetylcholine, whereas endothelial dysfunction is restricted to epicardial arteries in age-matched normocholesterolemic patients with evidence of coronary atherosclerosis and/or hypertension.

Coronary vasomotion in response to sympathetic stimulation in humans: importance of the functional integrity of the endothelium.

The coronary vasomotor response to the cold pressor test was studied with use of quantitative coronary angiography in 32 patients without evidence of coronary artery disease and 55 patients with such disease; in a subset of 22 patients (9 with normal coronary arteries and 13 with coronary artery disease), the effects of the cold pressor test were compared with the effects of the endothelium-dependent vasodilator acetylcholine with simultaneous intracoronary Doppler flow velocity measurements to assess the influence of endothelial dysfunction. The cold pressor test induced vasodilation of 8.9 +/- 5.7% in all 77 analyzed vessel segments of the group with normal arteries (p less than 0.01). In contrast, in patients with coronary artery disease, the 52 analyzed stenotic segments were constricted by -12.1 +/- 9.5% (p less than 0.01), the 57 analyzed vessel segments with luminal irregularities were constricted by -8.9 +/- 5.2% (p less 0.01) and 40 (85%) of 47 angiographically normal segments also were constricted by -7.0 +/- 4.9% (p less than 0.05). Preserved vasodilating capability was demonstrated by intracoronary nitroglycerin in all analyzed segments. In nine patients with normal coronary arteries, the analyzed vessel segments were dilated in response to both the cold pressor test and intracoronary acetylcholine by 10.9 +/- 5.4% and 13.4 +/- 4.7%, respectively. In contrast, in all 13 patients with coronary artery disease, vasoconstriction of identical vessel segments by -9.1 +/- 3.7% and -23 +/- 10.4%, respectively, was observed after both the cold pressor test and intracoronary acetylcholine. Intracoronary propranolol did not significantly affect either the vasodilative response in 11 normal coronary arteries (11.3 +/- 4.4% before and 8.6 +/- 4.3% after beta-blockade) or the vasoconstrictor response in 8 atherosclerotic coronary arteries (-11.4 +/- 4.6% before and -14.6 +/- 5.3% after beta-blockade). The dilation of normal and the constriction of atherosclerotic coronary arteries with cold pressor testing exactly mirror the response to the endothelium-dependent dilator acetylcholine. Endothelial dysfunction in coronary atherosclerosis resulted in a loss of normal dilator function and permitted vasoconstrictor responses to sympathetic stimulation. Thus, coronary vasomotion of large epicardial arteries in response to sympathetic stimulation by the cold pressor test in humans is intimately related to the integrity of endothelial function.

[Effect of x-rays on changes in electrolytes and metabolism of the myocardium. VI. Radiation-induced changes of catecholamine content]. / Untersuchungen über den Einfluss von Röntgenstrahlen auf Elektrolytverschiebungen und Stoffwechsel des Herzmuskels. VI. Strahlenbedingte Veränderungen des Katecholamingehaltes

In the myocardium of guinea-pigs, the behaviour of the catecholamines noradrenalin and adrenalin as well as the monoamine oxidase activity was biochemically studied following a local irradiation with 250 up to 6000 R surface dose. The noradrenalin content is significantly reduced already after a surface dose of 250 R. This drop of the noradrenalin content is beginning 15 min after irradiation, and not till 72 hours later, a complete normalization of the noradrenalin content is to be shown. A fractionated irradiation with twice 250 R SD in an interval of 24 hours leads to a further reduction. The changes of the adrenalin content are uncharacteristic, the activity of the monoamine oxidase is unaffected.