Frank C. Schoebel

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

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

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

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

Changes of hemostasis, endogenous fibrinolysis, platelet activation and endothelins after percutaneous transluminal coronary angioplasty in patients with stable angina.

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.

Vineberg graft: flow reserve of bilateral implantation after 27 years

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.

Konservative Therapieansätze bei terminaler koronarer Herzkrankheit

ZusammenfassungTrotz Fortschritten in der invasiven Revaskularisation und des unbestrittenen Erfolges der konventionellen antianginösen Therapie nimmt die Zahl von Patienten mit schwerer koronarer Herzkrankheit und einer therapierefraktären Beschwerdesymptomatik zu. Für die „therapierefraktären” Patienten wurde als eine antithrombotische Weiterentwicklung die chronisch-intermittierende Urokinasetherapie als ein neuartiges, mikrozirkulatorisch wirksames Therapieprinzip entwickelt, deren Wirkung auf einer Kombination aus rheologischen und fibrinolytischen Mechanismen sowie möglicherwiese auf einer Plaqueregression beruht.Das Koronarsyndrom der „therapierefraktären” Angina pectoris ist durch eine schwere, nicht revaskularisierbare koronare Herzkrankheit mit einer vergleichsweise nur gering eingeschränkten linksventrikulären Funktion gekennzeichnet. Vor der Indikationsstellung zur chronisch-intermittierenden Urokinasetherapie muß eine konsequente Ausschöpfung der konservativen Therapiemaßnahmen einschließlich zusätzlicher Therapiemaßnahmen wie der LDL-Cholesterinsenkung erfolgen, die nach aktuellen Daten eine antiischämische und somit potentiell antianginöse Wirksamkeit infolge einer Verbesserung der Endothelfunktion der epikardialen Leitungsgefäße aufweist.Neben einer in systematischen Untersuchungen objektivierbaren antiischämischen Wirksamkeit der chronisch-intermittiierenden Urokinasetherapie zeigen sich bei Patienten mit ischämischer Herzinsuffizienz darüber hinaus vielversprechende hämodynamische Therapieeffekte auf die diastolische und systolische Funktion unter Belastung. So konnten Ergebnisse der Radionuklidventrikulographie eine signifikante Steigerung der linksventrikulären Ejektionsfraktion unter Belastung aufzeigen. Eine Normalisierung diastolischer Funktionsparameter konnte ebeso nach zwölf Wochen chronisch-intermittierender Urokinasetherapie nachgewiesen werden. Diese antiischämischen und hämodynamischen Therapieeffekte führen zu einer eindrucksvollen Besserung der Lebensqualität dieser Patienten, so daß sich dieses aufwendige Therapieprinzip auch vor dem Hintergrund der in der Regel über zwölf Monate anhaltenden Wirkung rechtfertigt.SummaryDespite 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 longterm 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.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.

Fibrinogen: Pathogenetical and Therapeutical Implications in Atherosclerosis

In the pathogenesis of atherosclerosis, fibrinogen as the predominant clotting factor exerts its atherogenous effects through hemostatic and additional effects of blood flow. According to several epidemiologic studies fibrinogen has to be considered as a primary coronary risk factor comparable with other established risk factors, such as arterial hypertension and cho1estero1 .In patients with coronary artery disease, significantly elevated fibrinogen levels are found. Hyperfibrinogenemia can critically limit coronary blood flow in microcirculation due to fibrinogen-dependent increase in plasma viscosity and red-blood-cell aggregation- The importance of fibrinogen in microcirculatory blood flow can be demonstrated by the benefits of a reduction of plasma fibrinogen by fibrate therapy, e.g. fenofibrate treatment, LDL-cholesterol apheresis and a “chronically intermittent i/v urokinase therapy” in therapy-refractory patients with severe coronary artery disease.