Significance of left-sided heart disease for the detection of patent foramen ovale by transesophageal contrast echocardiography.

Detection of patent foramen ovale by contrast echocardiography is based on transient inversion (right atrial pressure higher than left atrial pressure) of the interatrial pressure gradient. Therefore, the presence of left-sided heart disease with potential elevation of left atrial pressure might obscure the diagnosis of patent foramen ovale. Accordingly, 150 patients (88 men, 62 women; mean age 51.7 +/- 15.2 years) were evaluated for a patent foramen ovale by transesophageal contrast echocardiography. Additionally, atrial septal motion during normal respiration and during the Valsalva maneuver was analyzed. Patency of the foramen ovale was observed in 20 (27%) of 74 patients without left-sided heart disease and with previous arterial embolism, in none (0%) of 25 patients with left-sided heart disease and embolism, in 7 (39%) of 18 patients without left-sided heart disease and without embolism and in 3 (9%) of 33 patients with left-sided heart disease and without embolism. The detection rate of patent foramen ovale was lower in patients with than without left-sided heart disease (5% vs. 29%, p = 0.0007) but was similar in patients with and without embolism (20% vs. 19.5%, p = NS). Abnormal atrial septal motion was more frequently observed in patients with left-sided heart disease (p = 0.0003) and was inversely correlated to detection of patent foramen ovale (p = 0.0003). Multivariate analysis revealed an independent association between the absence of left-sided heart disease and the detection of patent foramen ovale (p = 0.0003). These data suggest that in patients with left-sided heart disease, patency of the foramen ovale may be missed even by transesophageal contrast echocardiography.

Elevated lipoprotein(a) and increased incidence of restenosis after femoropopliteal PTA. Rationale for the higher risk of recurrence in females?

It has been shown that the incidence of recurrent stenosis following successful percutaneous transluminal coronary angioplasty (PTCA) is correlated with serum Lipoprotein(a) [Lp(a)] levels. The aim of the present study was to examine the influence of Lp(a) on restenosis after primary successful femoropopliteal PTA. One hundred and thirty nine consecutive patients with peripheral arterial occlusive disease (PAOD) and successful femoropopliteal PTA were studied. Follow-up included clinical examination and non-invasive laboratory testing (pulse volume recordings, ankle-brachial arterial pressure measurement) in every patient before and after 1, 3, 6 and 12 months following intervention. Duplex sonography was performed 1 year after PTA. Suspicion of restenosis (> or = 50% diameter reduction) was verified by angiography. Lp(a) was determined using ELISA technique (mg/dl). Twelve months after successful PTA no restenosis was found in 82 patients (59%: group A). The one-year recurrence rate of 41% (group B) was due to significant restenosis in 35 patients (25%) and reocclusion in 22 patients (16%). The corresponding mean values +/- S.E.M. for Lp(a) were as follows: group A, 28 +/- 5.3; group B 59 +/- 11 (P < 0.01). Women showed a higher frequency of recurrences (55%) versus men (30%, P < 0.01) also corresponding with a high Lp(a) level (51.8 +/- 8 versus 32.7 +/- 5; P < 0.05). Furthermore Lp(a) aggravated the well known increased risk for recurrence in multiple stenoses or occlusions of > or = 5 cm in length. There were no significant differences between groups A and B with respect to age, diabetes, hyperlipidaemia, obesity and cigarette smoking. The results support the view that Lp(a) is an independent risk factor for recurrence after PTA in the femoropopliteal area. It might also be a causal basis for the higher incidence of recurrences in female PAOD patients.

D-dimer and TAT measurement in patients with deep venous thrombosis: utility in diagnosis and judgement of anticoagulant treatment effectiveness.

The plasma levels of thrombin-antithrombin III-complexes (TAT) and the fibrin split product D-Dimer were measured in 39 patients with phlebographically proven acute DVT: 34 patients had proximal DVT, 5 had calf DVT. The sensitivity of D-Dimer and TAT measurements in the diagnosis of proximal DVT was found to be dependent on the duration of symptoms: 0 to 7 days (n = 27): elevated D-Dimer levels (greater than 120 ng/ml) = 1, D-Dimer Latex test positive (greater than 500 ng/ml) = 1, elevated TAT levels (greater than 6 ng/ml) = 0.88. Eight to 14 days (n = 7): elevated D-Dimer levels = 1, D-Dimer Latex test positive = 0.33, elevated TAT levels = 0.66; specificity: elevated D-Dimer: 0.48, D-Dimer Latex test: 1, elevated TAT: 0.76. Calf DVT patients (n = 5) had elevated D-Dimer levels, negative Latex tests and 3 of them had normal TAT values. Hemostatic and fibrinolytic parameters were also determined in 13 patients during heparin treatment of proximal DVT. Elevated D-Dimer and TAT levels rapidly decreased after initiation of anticoagulant therapy. In 2 of 13 patients a marked increase in D-Dimer and TAT levels was observed in periods of ineffective heparinization, documented by normal or only slightly prolonged thrombin clotting times. We conclude from our results that 1) D-Dimer EIA measurement, in contrast to TAT measurement, shows a very high sensitivity in the diagnosis of DVT, 2) due to low specificity this test can only be used to exclude thrombosis in patients with suspected DVT, and 3) the determination of the plasma levels of D-Dimer and TAT may be useful for judging the effect of anticoagulant treatment on thrombotic processes.

Levels of prothrombin fragment F1+2 in patients with hyperhomocysteinemia and a history of venous thromboembolism.

Increased thrombin generation occurs in many individuals with inherited defects in the antithrombin or protein C anticoagulant pathways and is also seen in patients with thrombosis without a defined clotting abnormality. Hyperhomocysteinemia (H-HC) is an important risk factor of venous thromboembolism (VTE). We prospectively followed 48 patients with H-HC (median age 62 years, range 26-83; 18 males) and 183 patients (median age 50 years, range 18-85; 83 males) without H-HC for a period of up to one year. Prothrombin fragment F1+2 (F1+2) was determined in the patient's plasma as a measure of thrombin generation during and at several time points after discontinuation of secondary thromboprophylaxis with oral anticoagulants. While on anticoagulants, patients with H-HC had significantly higher F1+2 levels than patients without H-HC (mean 0.52 +/- 0.49 nmol/l, median 0.4, range 0.2-2.8, versus 0.36 +/- 0.2 nmol/l, median 0.3, range 0.1-2.1; p = 0.02). Three weeks and 3, 6, 9 and 12 months after discontinuation of oral anticoagulants, up to 20% of the patients with H-HC and 5 to 6% without H-HC had higher F1+2 levels than a corresponding age- and sex-matched control group. 16% of the patients with H-HC and 4% of the patients without H-HC had either F1+2 levels above the upper limit of normal controls at least at 2 occasions or (an) elevated F1+2 level(s) followed by recurrent VTE. No statistical significant difference in the F1+2 levels was seen between patients with and without H-HC. We conclude that a permanent hemostatic system activation is detectable in a proportion of patients with H-HC after discontinuation of oral anticoagulant therapy following VTE. Furthermore, secondary thromboprophylaxis with conventional doses of oral anticoagulants may not be sufficient to suppress hemostatic system activation in patients with H-HC.

Hyperhomocysteinemia is a risk factor of recurrent venous thromboembolism.

Hyperhomocysteinemia is a risk factor of venous thromboembolism. The risk of recurrence in patients with hyperhomocysteinemia is unknown, and the optimal therapy for these patients after acute venous thromboembolism is uncertain. In a multicenter study, 264 patients with an objectively documented single episode of idiopathic venous thromboembolism were prospectively followed after discontinuation of oral anticoagulants. Patients were classified as hyperhomocysteinemic if their homocysteine levels exceeded the 95th percentile of the controls. The outcome events studied were objectively confirmed deep-vein thrombosis and/or pulmonary embolism. Homocysteine levels were elevated in 66 patients (25%) and normal in 198 patients (75%). Recurrent venous thromboembolism occurred in 12 of 66 patients with hyperhomocysteinemia (18.2%) and in 16 of 198 patients without hyperhomocysteinemia (8.1%). The cumulative probability of recurrence 24 months after discontinuation of oral anticoagulants was 19.2 percent (95 percent confidence interval 8.7-27) in patients with hyperhomocysteinemia and was 6.3 percent (95 percent confidence interval 2.4-10.1; p = 0.001) in those without hyperhomocysteinemia. The relative risk of recurrent thrombosis was higher in patients with hyperhomocysteinemia [RR 2.7 (1.3-5.8), p = 0.009]. Patients with hyperhomocysteinemia are at high risk of recurrent venous thromboembolism. The high prevalence of hyperhomocysteinemia in thrombosis patients together with the increased risk of recurrence warrants extended patient screening. The impact on the risk of recurrence of prolonged anticoagulation, supplementation of folate and vitamin B12, or both have to be investigated.

The risk of early recurrent venous thromboembolism after oral anticoagulant therapy in patients with the G20210A transition in the prothrombin gene.

A G20210A transition in the prothrombin gene is a common risk factor of venous thrombosis. The risk of recurrent venous thromboembolism in carriers of the 20210A allele is unknown and guidelines for secondary thromboprophylaxis in these patients are not available. In a prospective multicenter trial, 492 patients with a history of objectively documented venous thromboembolism were followed for a mean observation time of 24+/-16 months after discontinuation of oral anticoagulants. Forty-two patients (8.5%) were carriers of the 20210A allele. Three of the 42 patients with the G20210A mutation (7%) and 54 of 450 patients without the mutation (12%) experienced recurrent venous thrombosis. At 24 months, the probability of recurrence was 8% (95% CI 0-16.7) in patients with the mutation and was 12.2% (95% CI 8.8-15.6) in patients without the mutation. In conclusion, the risk of early recurrent venous thromboembolism is not higher in patients with the G20210A mutation than in those without the mutation. Therefore, long-term secondary thromboprophylaxis with oral anticoagulants in heterozygous carriers of the 20210A allele is not justified.

The risk of recurrent venous thromboembolism in patients with and without factor V Leiden.

Thromboprophylaxis with oral anticoagulants up to six months is established in patients after a first venous thromboembolic event (VTE). The risk of recurrent VTE is still considerable thereafter, and it is uncertain whether some patients might benefit from extended anti-coagulation. We performed a prospective, multicenter trial (4 thrombosis centers) and evaluated in 380 patients with a first or recurrent VTE (patients with a deficiency of antithrombin, protein C, protein S or plasminogen; cancer; or an antiphospholipid antibody syndrome were excluded) the risk of recurrence after discontinuation of secondary thromboprophylaxis with oral anticoagulants. It was the aim of the study to evaluate whether patients, with factor V Leiden are at an increased risk of recurrent VTE. 112 (29.5%) patients were carriers of factor V Leiden (26.9% heterozygous, 2.6% homozygous). After a median observation time of 19.3 months the overall recurrence rate of VTE was 9.9%. Recurrent deep vein thrombosis and/or pulmonary embolism occurred in 26 of 268 patients without factor V Leiden (9.7%) and in 10 of 112 patients with factor V Leiden (8.9%). The probability of recurrent VTE two years after discontinuation of oral anticoagulants was 12.4% (95% CI 7.8-17) in patients without factor V Leiden and was 10.6% (95% CI 3.8-17.4) in carriers of the mutation. This difference was statistically not significant. Patients with factor V Leiden are not at a higher risk of recurrent VTE within two years after discontinuation of oral anticoagulants than patients without factor V Leiden. Balancing the risk of recurrent VTE and bleeding from oral anticoagulants, patients with factor V Leiden are not likely to benefit from oral anticoagulant therapy extended beyond six months.

Prothrombin fragment F1+2 is not predictive for recurrent venous thromboembolism.

It would be important to estimate in advance the risk of recurrent thrombosis. Deficiencies of antithrombin, protein C or protein S, or resistance to activated protein C are associated with a biochemically detectable prethrombotic state. It is thus far unknown whether in patients with a history of thromboembolism but without a defined clotting abnormality a heightened coagulation activation is detectable. We investigated the value of prothrombin fragment F1+2 (F1+2) as a predictor of recurrent venous thromboembolism. Furthermore, we compared the F1+2 levels of thrombosis patients without a defined clotting defect to those of Factor V Leiden patients with a history of venous thrombosis and to those of healthy controls. 180 patients without a defined clotting abnormality and 73 patients with Factor V Leiden were prospectively followed after discontinuation of oral anticoagulants for venous thrombosis and F1+2 was measured at regular intervals. Recurrent venous thromboembolism occurred in 23 (9%) of the 253 patients. Before or at several time points after oral anticoagulants, no significant difference in F1+2 levels was found in patients with and without recurrent thrombosis. F1+2 levels at 3 weeks and prior to recurrence were not significantly different in both patient groups. Over a one-year observation period, F1+2 levels of both patients with and without Factor V Leiden were higher than those of the controls. No difference in F1+2 was seen between patients with and without Factor V Leiden. We conclude that monitoring of F1+2 is not suitable for identification of individuals at risk of recurrent venous thrombosis. Permanent hemostatic system activation is detectable both in patients with a defined abnormality of the clotting system and in patients in whom a particular defect has not (yet) been identified.

Lack of influence of low-dose acetylsalicylic acid (100 mg daily) on platelet survival time, beta-thromboglobulin and platelet factor 4 in patients with peripheral arterial occlusive disease.

In this study we investigated the influence of low-dose (100 mg daily) acetylsalicylic acid (ASA) on 111-In-platelet survival time (PST) and on plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF 4) in 30 patients (median age: 60 years) with arteriographically proven peripheral arterial occlusive disease in a chronic stable phase. We observed no significant changes of PST during therapy with ASA (weighted mean: 169.8----166 [median] hours; multiple hit: 168.3----170.6 hours), and also the plasma levels of beta-TG (median: 31.8----32.3 ng/ml) and of PF 4 (3.6----3.9 ng/ml) remained unchanged.

Prostanoids for intermittent claudication.

BACKGROUND: Peripheral arterial occlusive disease (PAOD) is a common cause of morbidity in the general population. While numerous studies have established the efficacy of prostanoids in PAOD stages III and IV the question of the role of prostanoids as an alternative or additive treatment in patients suffering from claudicatio intermittens (PAOD II) has not yet been clearly answered. OBJECTIVES: The aim of this review was to evaluate effects of prostanoids in patients with intermittent claudication. SEARCH STRATEGY: Computerised searches of the Cochrane Peripheral Vascular Diseases Specialised Register (last searched April 2003), The Cochrane Central Register of Controlled Trials (CENTRAL) (last searched Issue 1, 2003), MEDLINE and EMBASE were undertaken. In addition relevant journals were hand-searched. SELECTION CRITERIA: Randomized clinical trials describing the effects of prostanoids in the treatment of patients suffering from intermittent claudication have been considered for inclusion. DATA COLLECTION AND ANALYSIS: All reviewers assessed the quality of studies and extracted data unblinded. Statistical analysis including tests for heterogeneity and overall effect were performed by using MetaView of Review Manager 4.2. All numeric values are expressed as mean +/- Standard deviation (SD). MAIN RESULTS: Eighteen studies were included for analysis. A significant heterogeneity between the included studies was detected in most of the subgroup analysis. Five studies compared the effects of prostaglandin E1 (PGE1) versus placebo, and reported in their individual results significant increases in walking distances after the administration of PGE1. The attained increase in walking distances appears to be not merely a short-term effect because several studies reported that walking capacity remained increased even after termination of treatment. On the other hand, oral or intravenous prostacyclin did not increase the walking distances significantly. At least one adverse reaction was reported from 23.6% of the patients treated with prostacyclin (PGI2), and its analogues and from 13.7% of the patients treated with PGE1. REVIEWER'S CONCLUSIONS: Because of the heterogeneity between most of the included studies, we did not pool relevant parts of the data by meta-analysis. Based on the individual results of the published literature, patients with intermittent claudication seem to benefit from administration (intravenous or intra-arterial) of PGE1 by a significant improvement of their walking capacity. Further well-conducted randomized, double blinded trials, with a sufficient number of patients to provide statistical powerful information, should be performed to confirm the results of this review.

Color duplex sonography guided stent placement in a stenosis of the superficial femoral artery. A case report.

We report the first case of a successful stent placement under color coded ultrasound guidance alone in the superficial femoral artery of a 73-year-old woman suffering from intermittent calf claudication following restenosis after an uncomplicated angioplasty five months previously. Because of a hemodynamically residual stenosis after three attempts at dilatation, a percutaneous transluminal angioplasty and stent insertion were performed under the sole guidance of color coded ultrasound. The intervention was performed without complication and at the six-month follow-up examination, the patient was symptom-free and the stent was morphologically intact and hemodynamically functional. This case shows that successful stent placement under ultrasonic guidance alone, without fluoroscopic control is possible, provided that there is adequate sonographic visualization.

Effects of transvenous regional guanethidine block in the treatment of critical finger ischemia.

The objective of this study was to determine the effects of transvenous regional guanethidine block in the treatment of patients with critical finger ischemia. Twenty-seven patients (17 collagen vascular disease, four thromboangiitis obliterans, three embolism, three atherothrombosis) presenting with ischemic rest pain and/or ulcerations of the fingers received a single block with 5 mg guanethidine injected in 60 mL into the clinically more affected hand under 30 minutes of arterial arrest. Marked hyperemia was induced in the treated upper limb, increases (p < 0.01) in finger blood flow, finger skin temperature, and laser Doppler flux were higher and longer lasting than in forearm blood flow, persisting for a whole month. Effects in patients with ischemic finger ulcers were less pronounced than in those without, yet statistically significant increases of all evaluated parameters were observed in these patients too. No effects were seen in the contralateral untreated upper limb or in systemic blood pressure. Subjective symptoms (reduction of rest pain, numbness, vasospastic attacks) were improved in 25/27 (92.6%) patients, ischemic rest pain disappeared in 20/27 (74.1%), and complete healing of finger tip ulcerations within 1 month was achieved in 10/12 (83.3%) affected patients. No side effects were observed. This described method combines good clinical efficacy with lack of undesirable side effects and can be repeated easily. Therefore, this technique is recommended for broader clinical use.

[Fibropolycystic diseases of the liver and bile ducts--a case report and review of the literature]. / Fibropolyzystische Erkrankungen der Leber und der Gallenwege--Fallbericht und Literaturübersicht.

A case of congenital cystic dilatation of the intrahepatic bile ducts (Caroli's disease) is reported. This 20-year-old patient presented also with congenital hepatic fibrosis, fusiform dilatation of the common bile duct and cysts of the liver parenchyma, accompanied by medullary sponge kidneys. The dominant clinical feature was recurrent septic cholangitis. Clinical picture, as well as the diagnostic and therapeutic problems of the individual entities of hepatobiliary fibropolycystic disease are discussed. Although these belong to a family of closely related malformations, whereby involvement of different anatomic levels varies from case to case, such a complex combination as in this patient has not, to our knowledge, been reported before.

Thromboembolic complications in a patient with heparin-induced thrombocytopenia (HIT) showing cross-reactivity to a low molecular weight heparin-treatment with Org 10172 (Lomoparan).

Heparin-induced thrombocytopenia is an immuno-mediated life-threatening side effect of heparin therapy which poses difficulties in diagnosis and major therapeutic problems. Heparin must be instantly discontinued. We describe the case of a 60-year-old male patient with type II heparin-induced thrombocytopenia, complicated by progressive deep venous thrombosis and pulmonary embolism. He failed to improve when therapy was continued with a low molecular weight heparin (Fragmin) and high doses of intravenous immunoglobulins were administered. The test for heparin-dependent platelet aggregation was positive for unfractionated heparin and low molecular weight heparin, but negative for the heparinoid Org 10172. During subsequent anticoagulant therapy with Org 10172 for seven days the number of platelets increased rapidly and the patient recovered. Nine months later Org 10172 was used again in this patient for thrombosis prophylaxis without any adverse effects. In patients with heparin-induced thrombocytopenia requiring immediately acting anticoagulant therapy, Org 10172 can be considered as an effective alternative drug to unfractionated and low molecular weight heparins.

Prostanoids in the treatment of intermittent claudication--a meta-analysis.

BACKGROUND: Numerous studies have established the efficacy of prostanoids in PAD stages III and IV, but the role of prostanoids as an alternative or additive treatment in patients suffering from PAD II is less clear. To resolve this uncertainty we performed a meta-analysis of all randomised controlled studies analysing effects of prostanoids in patients suffering from intermittent claudication. METHODS: 96 studies have been screened by computerised searches of MEDLINE and EMBASE. Relevant studies were pooled in Cochrane's Review-manager 4.1. RESULTS: 19 studies were included for further analysis. Five studies could not be pooled for analysing walking distances, because standard deviations were not stated. Eight studies compared effects of any prostanoid i.v. vs. placebo. In total 557 patients (281/276) were included for analysis of painfree--walking distance (PFWD) and 519 patients (262/257) for analysis of maximum walking distance (MWD). Prostanoids compared to placebo significantly improved mean PFWD by 28% (7%-49%, P = 0.008) and mean MWD by 30% (11%-50%, P = 0.002). At least one adverse reaction was reported from 39.6% of the patients treated with prostacyclin and its analogues and from 13.7% of the patients treated with prostaglandin E1. CONCLUSION: Patients suffering from intermittent claudication benefit from administration of prostaglandin E1 by a significant improvement of their walking capacity.

[Macroembolism as a complication of ultra-high dose urokinase lysis of occlusion of a bifurcation prosthesis]. / Makroembolie als Komplikation bei ultrahochdosierter Urokinaselyse eines Bifurkationsprothesenverschlusses.

The case of a 70-year-old woman suffering from a long occlusion of the right branch of an aortobifemoral dacron-graft implanted six years ago is reported. Patency could be achieved by a systemic application of an ultrahigh dose of urokinase (UHUK = 9,000,000 I.U/6 h, intermittent daily application, two cycles). As a major complication macro-embolism to the popliteal artery and to the superficial femoral artery occurred, however. A further cycle of UHUK, local thrombolytic therapy (12 mg rtPA) and surgical thrombectomy failed to achieve persistent recanalization. So the patient finally had to be provided with a femoro-crural composite bypass. In conclusion, in a systemic thrombolytic therapy of occlusions of dacron grafts in the aorto-iliacal area a standard dose of urokinase (initial dose 600,000 I.U., maintenance dose 150,000 I.U./h, infusion pump) is recommended.

[Leriche syndrome: treatment with local lysis and subsequent percutaneous transluminal angioplasty]. / Leriche-Syndrom: Behandlung mit lokaler Lyse und anschliessender perkutaner transluminaler Angioplastie.

Two cases of Leriche's syndrome treated by local thrombolysis and subsequent percutaneous transluminal angioplasty with or without additional stent implantation are described. The fibrinolytic drugs were applied locally into the occlusions through a Mewissen Infusion Catheter and a Katzen Infusion Wire (initial 2.5 mg rt-PA as bolus followed by Urokinase (50000 IU/h) during 24 and 48 hours respectively. Residual stenotic lesions and occlusions were successfully treated with PTA alone in case 1 and with PTA in combination with a stent implantation in case 2. In accordance with Bean et al. (1985) and Goffette et al. (1989) we recommend local lysis in combination with PTA with or without additional stent implantation as an alternative treatment to surgery or systemic lysis for the treatment of Leriche's syndrome.

Ultrasound guided compression therapy in 134 patients with iatrogenic pseudo-aneurysms: advantage of routine duplex ultrasound control of the puncture site following transfemoral catheterization.

BACKGROUND: The following study was designed to evaluate the effectiveness and safety of ultrasound guided compression therapy (UGCT) of iatrogenic postcatheterization pseudo-aneurysms (PA) on the one hand and to justify the usefulness of the routine colour duplex control of the puncture site following transfemoral catheterization, on the other hand. MATERIAL AND METHODS: During the study period 142 patients with (PA) following transfemoral catheterization were identified by means of colour duplex examination Eighty of these 142 patients were identified during a routine colour duplex control of the puncture site the day after PTA/angiography because of peripheral arterial occlusive disease (PAOD) [group A]; the remaining 62 patients with symptomatic groins were referred from other departments [group B]. RESULTS: In 8 patients of group B UGCT was considered to be contra-indicated, they were primarily treated by surgical repair of the PA. A total of 134 patients (group A 80 patients, group B 54 patients) underwent an UGCT. In total the success rate of UGCT was in group A 100% and in group B 78%. 12/54 patients (all group B) with failure of UGCT underwent a secondary surgical repair of the PA. Within group B there was a negative correlation between delay of diagnosis/UGCT and success (p < 0.04), whereas the size of the sheath did not influence the outcome of the UGCT (p = 0.3). CONCLUSION: Our study confirms the effectiveness and safety of UGCT. Routine colour duplex control of the puncture site the day following the removal of the sheath after percutaneous catheterization and UGCT of PAs without delay can increase the success rate of UGCT and minimize the need for surgical repair of PAs.