Off-Pump-Koronarrevaskularisation

Adverse clinical consequences associated with conventional coronary artery bypass surgery (CCAB) have largely been attributed to cardiopulmonary bypass circuit (CPB), hypothermic cardiac arrest, aortic cannulation, and cross-clamping. Consequently, there has been a growing interest in safer alternatives to CCAB including off-pump beating-heart bypass surgery (OPCAB). Initial concerns regarding completeness of revascularization at the lateral wall were addressed by using modern stabilizers and heart positioning devices. First studies tended to be nonrandomized clinical reports rather than controlled clinical trials with the potential risk of unbalanced baseline characteristics leading to biases in favor of OPCAB. Since these early reports, several randomized trials including mixed-risk patient populations have been completed. Most of them failed to reveal superiority of OPCAB concerning mortality and major perioperative morbidity due to statistically underpowered design to detect clinically important but infrequent adverse outcome events. Likewise, in most of the recently published meta-analyses of randomized trials no difference in early mortality, myocardial infarction or stroke rate was found, but OPCAB was superior regarding blood loss, transfusion requirement, rethoracotomy, ventilation time, ICU (intensive care unit) and hospital stay and resource utilization as illustrated in Table 1. Most of the large observational studies comparing OPCAB and CCAB strategies demonstrated a benefit of OPCAB concerning early mortality, myocardial infarction and stroke rate as summarized in Table 2. However, in few published follow-up studies no significant differences concerning recurrence of angina, reintervention rate und late mortality were found. The decision between OPCAB and CCAB has to weigh several factors, including the likely risks and benefits of the two approaches for the particular patient, the experience of the surgeon, the complexity of the coronary disease, and the required coronary revascularization.     

Treatment of instent restenosis following stent-supported renal artery angioplasty.

OBJECTIVES: We prospectively studied the long-term outcome of endovascular treatment of instent renal artery stenosis (IRAS). BACKGROUND: Restenosis is a considerable drawback of stent-supported angioplasty of renal artery stenosis especially in small vessel diameters. The appropriate treatment strategy is not yet defined. PATIENTS AND METHODS: During a 10-year period 56 consecutive patients (65 lesions) with their first IRAS were included in a prospective follow-up program (mean follow-up 53 +/- 25 months, range 6-102). Primary endpoint of the study was the reoccurence of IRAS (>or= 70%) after primarily successful treatment of the first IRAS determined by duplex ultrasound. RESULTS: Primary success rate was 100%, no major complication occurred. Nineteen lesions were treated with plain balloon angioplasty (group 1, 30%), 42 lesions with stent-in-stent placement (group 2, 65%) using various bare metal balloon expandable stents, and 4 lesions with drug-eluting stent angioplasty (group 3, 6%). During follow-up, overall 21 lesions (32%) developed reoccurence of IRAS: n = 7/19 in group 1 (37%), n = 14/42 in group 2 (33%), and n = 0/4 in group 3 (0%; P = 0.573). Reoccurence of IRAS was more likely to occur in smaller vessel diameters than in larger ones [3-4mm: 4/7 (57%); 5 mm: 11/26 (42%); 6 mm: 5/25 (20%); 7 mm: 1/7 (14%), P = 0.088]. Multivariable analysis found bilateral IRAS and IRAS of both renal arteries of the same side in case of multiple ipsilateral renal arteries as independent predictors for reoccurence of IRAS. CONCLUSION: Treatment of IRAS is feasible and safe. The data demonstrate a nonsignificant trend towards lower restenosis with restenting of IRAS versus balloon angioplasty of IRAS. Individual factors influence the likelihood of reoccurence of IRAS.     

Novel mouse model of autosomal semidominant adult hypophosphatasia has a splice site mutation in the tissue nonspecific alkaline phosphatase gene Akp2.

Deactivating mutations in the TNSALP gene cause HPP. Akp2(-/-) mice model severe infantile HPP, but there is no model for the relatively mild adult form. Here we report on mice with an induced mutation in Akp2 that affects splicing. The phenotype of homozygotes mirror aspects of the adult form of HPP. INTRODUCTION: Hypophosphatasia (HPP) is a clinically varied skeletal disorder resulting from deficiency of tissue nonspecific alkaline phosphatase (TNSALP). Mice lacking Akp2 model infantile HPP characterized by skeletal hypomineralization, impaired growth, seizures, and perinatal mortality. No animal model exists to study the less severe forms of the disease that typically present in later life. MATERIALS AND METHODS: N-ethyl-N-nitrosourea (ENU) mutagenesis was used to generate mouse models of human disease. A mouse with low plasma alkaline phosphatase (ALP) activity was identified by our clinical chemistry screen. Its offspring were used for inheritance studies and subjected to biochemical, histological, and radiological phenotyping. DNA was extracted for mapping and osteoblasts harvested for functional studies. RESULTS: We showed semidominant inheritance of the low ALP phenotype and mapped the underlying point mutation to Akp2. Affected offspring bear the splice site mutation 862 + 5G>A-a hypomorphic allele named Akp2(Hpp). The same mutation has been reported in a patient. Akp2(Hpp/+) mice have approximately 50% of normal plasma ALP but display no other biochemical or skeletal abnormalities. Unlike Akp2(-/-) mice, Akp2(Hpp/Hpp) mice have normal initial skeletal development and growth, a normal lifespan and do not have seizures. TNSALP is low but detectable in Akp2(Hpp/Hpp) plasma. Osteoblasts display approximately 10% of normal ALP activity and reduced intracellular inorganic phosphate levels, yet are capable of normal mineralization in vitro. TNSALP substrates are significantly elevated in urine (inorganic pyrophosphate and phosphoethanolamine) and plasma (pyridoxal 5'-phosphate), whereas plasma inorganic pyrophosphate levels are normal. Akp2(Hpp/Hpp) mice develop late-onset skeletal disease, notably defective endochondral ossification and bone mineralization that leads to arthropathies of knees and shoulders. CONCLUSIONS: Akp2(Hpp/Hpp) mice mirror a number of clinical features of the human adult form of HPP. These mice provide for the first time an animal model of late onset HPP that will be valuable in future mechanistic studies and for the evaluation of therapies such as those aimed at HPP.     

Acute and long-term outcome of endovascular therapy for aortoiliac occlusive lesions stratified according to the TASC classification: a single-center experience

PURPOSE: To compare acute and long-term outcomes of endovascular therapy for TASC (TransAtlantic Inter-Society Consensus) A and B lesions versus TASC C and D lesions. METHODS: Based on a prospectively maintained database, a retrospective analysis was conducted of 375 symptomatic patients (335 men; mean age 63+/-8 years) who underwent 438 interventions for aortoiliac arterial obstructions. Lesions were stratified according to the TASC II classification: 259 (59%) procedures involved TASC A/B lesions, while 113 (26%) were for TASC C and 66 (15%) for TASC D lesions. RESULTS: The baseline characteristics of patients with TASC A/B lesions differed significantly in the ankle-brachial index (ABI), occurrence of renal insufficiency, and lesion characteristics from those with TASC C or D lesions. Acute treatment success, defined as residual stenosis <30%, was 100%, 96%, 93%, and 100% for TASC A, B, C, and D lesions, respectively. The primary 1-year patency rate, which was 86% for the entire study cohort, was similar for all TASC classifications (89%, 86%, 86%, 85% for TASC A to D lesions, respectively). In the TASC A/B cohort, the 5-year event-free survival (70%) was not significantly better than in the C/D cohort (57%, p=0.124). The clinical outcome, as measured by Rutherford stage and ABI, improved significantly in all TASC subgroups after successful intervention and was maintained up to 1 year. Stenting was an independent predictor for lower restenosis rates (HR 0.517, 95% CI 0.317 to 0.842; p=0.008). CONCLUSION: In experienced hands, endovascular therapy of aortoiliac lesions can be successfully performed with sustained long-term outcome independent of the TASC II classification, even in class D lesions.     

Long-term results after directional atherectomy of femoro-popliteal lesions.

OBJECTIVES: Our objective in this research was the evaluation of the long-term results after directional atherectomy using the Silverhawk device (FoxHollow Technologies, Redwood City, California) of femoro-popliteal lesions. BACKGROUND: Considering reports on stent fractures in femoro-popliteal arteries, atherectomy may be a valuable alternative to stenting. METHODS: Eighty-four patients with 100 legs and 131 lesions with peripheral occlusive disease Rutherford categories 2 to 5 were included in a prospective registry. Forty-five lesions were de novo lesions (group 1; 34%), 43 lesions native vessel restenoses (group 2; 33%), and 43 lesions in-stent restenoses (group 3; 33%). Additional low pressure balloon angioplasty was used in 78 of 131 lesions (59%) and stenting in 8 lesions (6%). RESULTS: Technical success rate was 86% for atherectomy only and 100% after additional therapy. Mean lesion length was 43 +/- 54 mm, 105 +/- 122 mm, and 131 +/- 111 mm for group 1, group 2, and group 3, respectively (p < 0.001). Primary patency, defined as freedom of a >50% restenosis detected by duplex, was 84%, 54%, and 54% at 12 months (p = 0.002) and 73%, 42%, and 49%, at 18 months (p = 0.008); secondary patency rates were 100%, 93%, and 91% at 12 months (p = NS) and 89%, 67%, and 79% at 18 months (p = 0.001), respectively; and target lesion revascularization rate was 16%, 44%, and 47% at 12 months and 22%, 56%, and 49% at 18 months (p = 0.003 each) for group 1, group 2, and group 3, respectively. The only independent predictor for restenosis was treatment of restenotic lesions. Ankle-brachial index was significantly improved after 12 months and 18 months in all groups. CONCLUSIONS: Long-term technical and clinical results after directional atherectomy of femoro-popliteal lesions are in favor of de novo lesions compared with restenotic lesions.