DISSECT: a new mnemonic-based approach to the categorization of aortic dissection.

OBJECTIVE/BACKGROUND: Classification systems for aortic dissection provide important guides to clinical decision-making, but the relevance of traditional categorization schemes is being questioned in an era when endovascular techniques are assuming a growing role in the management of this frequently complex and catastrophic entity. In recognition of the expanding range of interventional therapies now used as alternatives to conventional treatment approaches, the Working Group on Aortic Diseases of the DEFINE Project developed a categorization system that features the specific anatomic and clinical manifestations of the disease process that are most relevant to contemporary decision-making. METHODS AND RESULTS: The DISSECT classification system is a mnemonic-based approach to the evaluation of aortic dissection. It guides clinicians through an assessment of six critical characteristics that facilitate optimal communication of the most salient details that currently influence the selection of a therapeutic option, including those findings that are key when considering an endovascular procedure, but are not taken into account by the DeBakey or Stanford categorization schemes. The six features of aortic dissection include: duration of disease; intimal tear location; size of the dissected aorta; segmental extent of aortic involvement; clinical complications of the dissection, and thrombus within the aortic false lumen. CONCLUSION: In current clinical practice, endovascular therapy is increasingly considered as an alternative to medical management or open surgical repair in select cases of type B aortic dissection. Currently, endovascular aortic repair is not used for patients with type A aortic dissection, but catheter-based techniques directed at peripheral branch vessel ischemia that may complicate type A dissection are considered valuable adjunctive interventions, when indicated. The use of a new system for categorization of aortic dissection, DISSECT, addresses the shortcomings of well-known established schemes devised more than 40 years ago, before the introduction of endovascular techniques. It will serve as a guide to support a critical analysis of contemporary therapeutic options and inform management decisions based on specific features of the disease process.

Aortic dissection and malperfusion syndrome: a when, what and how-to guide.

Malperfusion syndrome is a complication of aortic dissection caused by branch-vessel involvement and resulting in end-organ ischaemic dysfunction. Clinical diagnosis is mandatory, and imaging plays a critical role in confirmation and treatment planning. Radiologists must focus on detecting complications (findings of aortic dilation, rupture, organ ischaemia, etc.) and defining vascular compromise and associated malperfusion mechanisms. All these factors guide the multidisciplinary discussion concerning patient management and the suitability of endovascular treatment. Application of dedicated imaging protocols is mandatory in order to answer clinical and anatomical questions. Endovascular therapy has taken a predominant role in the therapeutic management of malperfusion syndrome with aortic fenestration, peripheral stenting and stent-grafting, all of which are procedures within the domain of expertise of current interventional radiologists. The purpose of this editorial is to present a when, what and how-to guide for all radiologists who encounter complicated aortic dissection.

Vascular endothelial growth factor enhances atherosclerotic plaque progression.

Vascular endothelial growth factor (VEGF) can promote angiogenesis but may also exert certain effects to alter the rate of atherosclerotic plaque development. To evaluate this potential impact on plaque progression, we treated cholesterol-fed mice doubly deficient in apolipoprotein E/apolipoprotein B100 with low doses of VEGF (2 microg/kg) or albumin. VEGF significantly increased macrophage levels in bone marrow and peripheral blood and increased plaque area 5-, 14- and 4-fold compared with controls at weeks 1, 2 and 3, respectively. Plaque macrophage and endothelial cell content also increased disproportionately over controls. In order to confirm that the VEGF-mediated plaque progression was not species-specific, the experiment was repeated in cholesterol-fed rabbits at the three-week timepoint, which showed comparable increases in plaque progression.

Variations of two pools of glycogen and carbohydrate in Saccharomyces cerevisiae grown with various ethanol concentrations.

Glycogen, a major reservoir of energy in Saccharomyces cerevisiae, is found to be present as soluble and membrane-bound insoluble pools. Yeast cells can store excess glycogen when grown in media with higher concentration of sugar or when subjected to nutritional stress conditions. Saccharomyces cerevisiae NCIM-3300 was grown in media having ethanol concentrations up to 12% (v/v). The effects of externally added ethanol on glycogen and other carbohydrate content of yeast were studied by using alkali digestion process. Fermentative activities of cells grown in the presence of various ethanol concentrations (2-8% v/v) exhibited increase in values of glycogen and other carbohydrate, whereas cells grown with higher concentrations of ethanol (10-12% v/v) exhibited depletion in glycogen and carbohydrate content along with decrease in cell weight. Such inhibitory effect of ethanol was also exhibited in terms of reduction in total cell count of yeast grown in media with 2-16% (v/v) ethanol and 8% (w/v) sugar. These data suggest that, as the plasma membrane is a prime target for ethanol action, membrane-bound insoluble glycogen might play a protective role in combating ethanol stress. Elevated level of cell-surface alpha-glucans in yeast grown with ethanol, as measured by using amyloglucosidase treatment, confirms the correlation between ethanol and glycogen.

Thrombomodulin overexpression to limit neointima formation.

BACKGROUND-These studies were initiated to confirm that high-level thrombomodulin overexpression is sufficient to limit neointima formation after mechanical overdilation injury. METHODS AND RESULTS-An adenoviral construct expressing thrombomodulin (Adv/RSV-THM) was created and functionally characterized in vitro and in vivo. The impact of local overexpression of thrombomodulin on neointima formation 28 days after mechanical overdilation injury was evaluated. New Zealand White rabbit common femoral arteries were treated with buffer, viral control, or Adv/RSV-THM and subjected to mechanical overdilation injury. The treated vessels (n=4 per treatment) were harvested after 28 days and evaluated to determine intima-to-media (I/M) ratios. Additional experiments were performed to determine early (7-day) changes in extracellular elastin and collagen content; local macrophage, T-cell, and neutrophil infiltration; and local thrombus formation as potential contributors to the observed impact on 28-day neointima formation. The construct significantly decreased neointima formation after mechanical dilation injury in this model. By histological analysis, buffer controls exhibited mean I/M ratios of 0.76+/-0.06%, whereas viral controls reached 0.77+/-0.08%; in contrast, Adv/RSV-THM reduced I/M ratios to 0.47+/-0.06%. Local inflammatory infiltrate decreased in the Adv/RSV-THM group relative to controls, whereas matrix remained relatively preserved. Rates of early thrombus formation also decreased in Adv/RSV-THM animals. CONCLUSIONS-This construct thus offers a viable technique for promoting a locally neointima-resistant small-caliber artery via decreased thrombus bulk, normal matrix preservation, and decreased local inflammation without the inflammatory damage that has limited many other adenoviral applications.

Effect of human recombinant vascular endothelial growth factor165 on progression of atherosclerotic plaque.

OBJECTIVES: This study was designed to evaluate the impact of recombinant human vascular endothelial growth factor165 (rhVEGF) on atherosclerotic plaque progression. BACKGROUND: Therapeutic angiogenesis represents a promising treatment for ischemic diseases. However, angiogenesis may impact atherosclerosis. METHODS: Albumin or rhVEGF was administered by a single intramuscular injection (2 microg/kg body weight) to New Zealand White rabbits fed with a 0.25% cholesterol diet beginning three weeks before therapy. Subsets of rabbits from each group underwent perfusion-fixation and harvesting of the thoracic aorta for morphometric and immunohistochemical analyses at 7 or 21 days. RESULTS: The mean plaque area was 15.75+/-2.28% and 22.00+/-3.24% with VEGF and 0.67+/-0.22% and 1.17+/-0.34% with albumin at 7 and 21 days, respectively. The plaque circumference was 13.00+/-2.58% and 23.75+/-2.86% with VEGF and 2.50+/-0.65% and 6.25+/-1.88% with albumin at 7 and 21 days, respectively. The maximal plaque thickness was 0.11+/-0.002 and 0.15+/-0.007 mm with VEGF and 0.04+/-0.009 and 0.07+/-0.003 mm with albumin at 7 and 21 days, respectively. The endothelial density (reported as percent total plaque area) was 31.75+/-4.42% and 63.00+/-8.45% with VEGF and 7.75+/-1.65% and 12.75+/-1.93% with albumin at 7 and 21 days, respectively. The macrophage density was 4.5+/-0.86 and 19.25+/-1.54 with VEGF and 4.26+/-0.75 and 6.00+/-1.08 with albumin at 7 and 21 days, respectively. CONCLUSIONS: Recombinant human VEGF increases the rate and degree of atherosclerotic plaque formation in the thoracic aorta in a cholesterol-fed rabbit model.

High-efficiency endovascular gene delivery via therapeutic ultrasound.

OBJECTIVES: We studied enhancement of local gene delivery to the arterial wall by using an endovascular catheter ultrasound (US). BACKGROUND: Ultrasound exposure is standard for enhancement of in vitro gene delivery. We postulate that in vivo endovascular applications can be safely developed. METHODS: We used a rabbit model of arterial mechanical overdilation injury. After arterial overdilation, US catheters were introduced in bilateral rabbit femoral arteries and perfused with plasmidor adenovirus-expressing blue fluorescent protein (BFP) or phosphate buffered saline. One side received endovascular US (2 MHz, 50 W/cm2, 16 min), and the contralateral artery did not. RESULTS: Relative to controls, US exposure enhanced BFP expression measured via fluorescence 12-fold for plasmid (1,502.1+/-927.3 vs. 18,053.9+/-11,612 microm2, p < 0.05) and 19-fold for adenovirus (877.1+/-577.7 vs. 17,213.15+/-3,892 microm2, p < 0.05) while increasing cell death for the adenovirus group only (26+/-5.78% vs. 13+/-2.55%, p < 0.012). CONCLUSIONS: Endovascular US enhanced vascular gene delivery and increased the efficiency of nonviral platforms to levels previously attained only by adenoviral strategies.

Deaths due to hanging among adolescents - A 10-year retrospective study.

The present study was carried out to analyze various factors associated with death due to hanging among adolescents and to identify the areas of intervention for preventing such deaths. A retrospective study was carried out on 51 cases of adolescent deaths due to hanging, the autopsies of which were conducted by the Department of Forensic Medicine, Dr Shankarrao Chavan Government Medical College, Nanded, Maharashtra State (India), during the period between 1 January 2001 and 31 December 2010. In the present study, death by hanging among the adolescent age group was most commonly suicidal (96.08%) in nature, and only two (3.92%) cases of deaths due to accidental hanging were observed. Of the total number of suicidal deaths due to hanging among adolescents, the majority (80.39%) were among the older adolescent (15-19 years) age group. Rope and clothing items were commonly used ligature materials for committing suicide by hanging. Females outnumbered male victims (M:F ratio 1:1.13) among adolescents, contrary to the male preponderance observed among victims of the older age group (M:F ratio 1:0.44). Most of the suicidal deaths due to hanging (83.67%) among adolescents were observed at the victims' home. The predisposing and precipitating factors observed were domestic strife, examination-related stress, and physical and psychological illness.

Electron microscopic demonstration of lysosomal inclusion bodies in lung, liver, lymph nodes, and blood leukocytes of patients with amiodarone pulmonary toxicity.

The mechanism of amiodarone-induced pulmonary toxicity is unknown. Two cases of amiodarone pulmonary toxicity are presented in which abnormal inclusion bodies containing whorls of membrane were seen on electron microscopy of extrapulmonary tissues. These cytoplasmic lysosomal inclusion bodies were observed in lymphocytes, plasma cells, granulocytes, tissue macrophages, and hepatocytes. These widespread histopathologic changes in extrapulmonary tissues and in a variety of cell types are similar to more extensively investigated findings in animal models that are thought to represent a drug-induced lysosomal storage disease, phospholipidosis.

Endovascular treatment of hepatic venous outflow obstruction after piggyback technique liver transplantation.

BACKGROUND: The piggyback technique of orthotopic liver transplantation is an attractive alternative that preserves the recipient inferior vena cava and allows uninterrupted venous blood return during the anhepatic phase. As with other transplantation techniques, the vascular anastomoses required by the piggyback technique can develop strictures. METHODS: Review of records of 264 piggyback transplantations revealed two cases of delayed-onset hepatic venous obstruction from anastomotic strictures. Both patients also had symptoms of inferior vena cava obstruction, with azotemia and lower extremity edema. Both patients were treated percutaneously with balloon-expandable stents. RESULTS: Rapid, dramatic resolution of symptoms was achieved in both patients. Patients remain completely asymptomatic at 39 and 3 months of follow-up. CONCLUSIONS: Hepatic venous anastomotic strictures in recipients of piggyback technique transplants are a very uncommon complication. They may be easily and effectively treated by minimally invasive endovascular intervention.

Superior vena cava syndrome after heart transplantation: percutaneous treatment of a complication of bicaval anastomoses.

OBJECTIVES: Our objectives were (1) to investigate the incidence and cause of symptomatic superior vena caval anastomotic stenosis and central venous thrombosis in patients receiving heart or heart-lung transplantation and (2) to explore percutaneous methods of thrombolysis and endoluminal intervention to treat these complications. METHODS: Review of 1016 cases revealed three cases of superior vena cava syndrome. Anatomy, surgical technique, and medical risk factors were examined. Percutaneous treatments, including urokinase thrombolysis, mechanical thrombolysis, balloon angioplasty, and stent placement, were attempted. RESULTS: All three of these patients underwent transplantation by means of the bicaval anastomotic technique. In addition, the diameters of the donor and recipient cavae were grossly mismatched in all three. Stenoses in all three patients were successfully treated percutaneously with balloon angioplasty and stent placement. Treatment of the accompanying large-volume thrombosis was problematic in these patients, and two had hemorrhagic complications of urokinase thrombolysis. A mechanical thrombolysis device was used successfully in the third patient. CONCLUSIONS: Anastomotic stricture and central venous thrombosis is an uncommon complication of the bicaval anastomotic technique of heart and heart-lung transplantation. Discrepancy between donor and recipient caval diameters appears to be the major risk factor. Endoluminal thrombolysis and stenting provides rapid and enduring relief of symptoms and precludes repeat sternotomy, cardiopulmonary bypass, and general anesthesia.

Endovascular stent-graft repair of thoracic aortic aneurysms.

Conventional repair of aneurysms of the descending thoracic aorta entails thoracotomy and graft interposition. For elderly patients and those with previous operations, obesity, respiratory insufficiency, or other comorbidities, such a procedure entails significant mortality and morbidity. Transluminal stent-graft placement offers an alternative approach with potentially less morbidity and quicker recovery; however, the effectiveness and durability of stent-grafts remain uncertain. METHODS: Since July 1992, thoracic aortic stent-grafts have been placed in 44 patients with a variety of pathologic conditions. Each graft was individually constructed from self- expanding, stainless-steel Z stents covered with a woven Dacron polyester fabric graft. Craft dimensions were determined from spiral computed tomographic scans. All implants were performed in the operating theater under fluoroscopic and transesophageal echocardiographic guidance. Follow-up was by computed tomography and contrast angiography in all cases. PATIENT DATA: There were 36 men and 8 women. Mean age was 66 years (range 35 to 88 years). Mean aneurysmal diameter was 6.3 cm (range 4.0 to 9.4 cm). Etiologies included 23 degenerative aneurysms, four posttraumatic aneurysms, four pseudoaneurysms, and one chronic aortic dissection. RESULTS: There were three early deaths (<30 days) and two late deaths. One early death resulted from graft failure. There were two instances of paraparesis or paraplegia, with one associated early death. A single stent was deployed in 27 patients, two stents were required in 14 patients, and three stents were required in three patients. In 23 patients, vascular access was attained through the femoral artery; abdominal aortic access, either native or graft, was necessary in the remaining 21 patients. Twelve grafts were placed in conjunction with open abdominal aortic surgical procedures. Mean follow-up (98% complete) was 12.6 months (range 1 to 34 months). One late death occurred from aneurysmal expansion and rupture in a patient with a persistent midgraft leak. The second late death may have resulted from aneurysmal rupture. Immediate thrombosis was achieved in 36 patients, and late thrombosis was achieved in three others. Failure to achieve complete aneurysmal thrombosis occurred in five patients, however, and one individual (previously noted) died of aneurysmal expansion and rupture; the remaining four are being carefully monitored. Only one patient has required conversion of the stent to an open procedure; a contained rupture of the false lumen of a chronic dissection eventually necessitated total descending thoracic aortic exclusion. CONCLUSIONS: These early results support the hypothesis that endovascular stent-graft placement may be a safe and durable treatment for selected patients with aneurysmal disease of the descending thoracic aorta. Large introducer size (26F outer diameter) and relatively limited angulation capability, as well as imprecise deployment techniques, currently limit its applicability. Distal embolization and stent migration have not been observed. Failure to achieve complete aneurysmal thrombosis may allow continued aneurysmal expansion and rupture. Further follow-up is clearly necessary to evaluate the true long-term effectiveness of this procedure.

Percutaneous balloon fenestration and stenting for life-threatening ischemic complications in patients with acute aortic dissection.

OBJECTIVES: Acute aortic dissection frequently causes life-threatening ischemia of end-organs, historically associated with mortality exceeding 60%. Reperfusion with the use of interventional radiologic methods has evolved as a promising treatment. We report results of our initial 6 years of experience with percutaneous balloon fenestration of the intimal flap and endovascular stenting. METHODS: Forty patients (32 male and 8 female) with a median age of 53 years (range 16-86 years) underwent percutaneous treatment for peripheral ischemic complications of 10 type A and 30 type B acute aortic dissections since 1991. Twenty patients had ischemia of multiple organ systems. Thirty patients had renal, 22 had leg, 18 had mesenteric, and 1 had arm ischemia. RESULTS: Fourteen patients were treated with stenting of either the true or false lumen combined with balloon fenestration of the intimal flap, 24 with stenting alone, and 2 with fenestration alone. Successful revascularization was achieved in 93% +/- 4% (+/-70% confidence levels) of patients (37/40). Nine patients had procedure-related complications. The 30-day mortality rate was 25% +/- 7% (10/40), often related to irreversible ischemia of intra-abdominal organs that was present before the procedure. Of the remaining 30 patients, 5 have died and the remaining 25 continue to have relief of ischemic symptoms at a mean follow-up of 29 months. CONCLUSION: Percutaneous balloon fenestration of the intimal flap and endovascular stenting is an effective treatment for life-threatening ischemic complications of acute aortic dissection.

The "first generation" of endovascular stent-grafts for patients with aneurysms of the descending thoracic aorta.

OBJECTIVE: Our goal was to determine whether endovascular stent-grafting is feasible and effective for patients with aneurysms of the descending thoracic aorta. METHODS: Starting in July 1992, we conducted a prospective, uncontrolled clinical trial in 103 patients (mean age 69 years [range 34-89 years]) who underwent endovascular treatment of aneurysms of the descending thoracic aorta using a custom-fabricated, self-expanding stent-graft device. Follow-up was 100% complete and averaged 22 months. Sixty-two patients (60%) were judged not to be reasonable candidates for a conventional "open" surgical procedure. RESULTS: Complete thrombosis of the aneurysm was ultimately achieved in 86 (83%) patients. The early mortality rate was 9% +/- 3% (+/- 70% CL). Multivariable analysis revealed that myocardial infarction or stroke was linked with a higher likelihood of early death (P = .001). Early serious complications included paraplegia in 3% +/- 2% and stroke in 7% +/- 3%. Actuarial survival estimates at 1 year and 2 years were 81% +/- 4% and 73% +/- 5% (+/- 1 SE), respectively; being judged not to be a surgical candidate portended a higher probability of death (P = .003). According to the intent-to-treat principle, "treatment failure" (including all late sudden unexplained deaths) occurred in 38 patients; 53% +/- 10% of patients were free from treatment failure at 3.7 years. Stent-graft related complications occurred commonly and were linked with several anatomic, technical, and patient-related risk factors. CONCLUSIONS: This 5-year clinical trial involving use of a "first generation" device indicates that endovascular stent-grafting of descending thoracic aortic aneurysms is feasible with acceptable medium-term results. More refined, commercially developed devices available today offer less traumatic and more precise stent-graft deployment; these major technical advantages, coupled with important lessons we have learned over time and better patient selection, should be associated with more salutary clinical results in the future.

Development of a platform to evaluate and limit in-stent restenosis.

The objective of this work was to develop a platform to evaluate and deliver putative therapeutic agents for in-stent restenosis. Arterial stenting is applied in more than 60% of balloon angioplasties for treating cardiovascular disease. However, stented arteries encounter accelerated rates of restenosis. No prior platform has allowed evaluation or local management of in-stent restenosis without perturbing the very system being examined. A stainless steel, balloon-expandable stent was modified to serve as an ablumenal drug delivery platform. Several combinations of bioerodible polymer microspheres and gels were evaluated for channel retention under in vitro flow and in vivo conditions. A stent-anchored hybrid system prevented material embolization under all conditions. Unlike prior platforms, these stents do not alter local inflammation or in-stent plaque formation relative to conventional Palmaz-Schatz stents after in vivo deployment. The system also proved sensitive enough to detect plaque reduction with an antirestenotic agent. We conclude that a platform to evaluate and deliver therapeutic agents for in-stent restenosis has been achieved.

Endovascular stent-grafting after arch aneurysm repair using the "elephant trunk".

A 68-year-old woman with severe chronic obstructive pulmonary disease, aortic valvular insufficiency, and diffuse thoracic aortic aneurysm underwent aortic valve replacement and separate Dacron graft replacement of the ascending aortic and arch aneurysms using the elephant trunk technique. She was discharged on the tenth postoperative day. Five months later, she underwent endovascular stent-graft repair of the descending thoracic aortic aneurysm. She recovered uneventfully, and was discharged on the third postoperative day. Follow-up computed tomography at 6 months demonstrated exclusion of all flow into the descending thoracic aortic aneurysm. The elephant trunk technique followed by endovascular stent-grafting of the descending thoracic component is a potential therapeutic option in selected high-risk patients with diffuse aortic aneurysmal disease.

Thoracic aortic aneurysm repair with an endovascular stent graft: the "first generation".

OBJECTIVE: The feasibility and efficacy trial of an endovascular stent-grafting system for the treatment of aneurysms of the descending thoracic aorta was investigated. METHODS: After Institutional Review Board approval, 103 patients (mean age 69 years) underwent stent graft repair of a descending thoracic aortic aneurysm between July 1992 and November 1997. The stent graft was fabricated using self-expanding "Z" stents covered by a woven Dacron tube graft. Follow-up, which averaged 22 months, was 100% complete. Simultaneous open abdominal aortic aneurysm repair was performed in 19 patients. RESULTS: Complete aneurysm thrombosis was achieved in 86 patients (83%). Early mortality, defined as a death during the same hospitalization or in less than 30 days, was 9 +/- 3%, and was significantly associated with preoperative cerebrovascular accident (CVA) or myocardial infarction. Major perioperative morbidity occurred in 31 patients, and included paraplegia in 3, CVA in 7, and respiratory insufficiency in 12 patients each. Actuarial survival was 81 +/- 4% at 1 year, and 73 +/- 5% at 2 years. Treatment failure (including all late, sudden, unexplained deaths) occurred in 38 patients, and only 53 +/- 10% of patients were free of treatment failure at 3.7 years. Five patients required late operative therapy for endoleaks associated with aneurysm enlargement. CONCLUSIONS: Satisfactory results were achieved using this "first-generation" homemade stent graft device. Mortality and morbidity occurred frequently, but may have been associated with the high-risk character of this patient population. Medium-term results were acceptable, but continued aortic enlargement, with the late development of endoleaks, is a significant concern. Second-generation devices with commercial development, coupled with this initial experience, should allow improved clinical results in the future. Longer term follow-up is still necessary to fully define the efficacy of this endovascular approach.

Covered stent placement for neurovascular disease.

We describe an endovascular technique in which covered stents were used to occlude a parent vessel. In one patient, with a giant paraclinoid aneurysm, a Gortex-covered Palmaz stent was used to occlude the cervical internal carotid artery and to create thrombosis in the aneurysm. In the second patient, with a high-flow vertebrojugular fistula, a hooded stent provided definitive treatment after an attempt to close the fistula by detachable balloon therapy failed. Follow-up of these patients revealed stable stent position and no untoward effects of permanent vessel occlusion.

Current status of three-dimensional spiral CT scanning for imaging the vasculature.

Three-dimensional CT angiography is a new modality for minimally invasive vascular imaging. Meticulous attention to technique is critical to optimizing image quality and achieving diagnostic images. In this article, the properties of spiral CT acquisitions, intravenous contrast delivery, and three-dimensional rendering techniques, as they pertain to the optimization of CT angiograms, are discussed. Next, a review of initial investigations into the clinical applicability of CT angiography in the cranium, neck, chest, abdomen, and pelvis is provided. Finally, CT angiography is compared with MR angiography and conventional angiography.