Fred A. Weaver

Surgical revascularization versus thrombolysis for nonembolic lower extremity native artery occlusions: Results of a prospective randomized trial

PURPOSE Early results of a prospective study that compared surgical revascularization and thrombolysis for lower extremity arterial and graft occlusions have been published. This report details the final results in patients who have native artery occlusions. METHODS Two hundred thirty-seven patients who had lower extremity ischemia as a result of iliac-common femoral (IF; 69 patients) or superficial femoral-popliteal (FP; 168 patients) occlusion, and had symptomatically deteriorated within the past 6 months were randomized to catheter-directed thrombolysis (150 patients) or surgical revascularization (87 patients). After diagnostic arteriographic examination but before randomization, the optimal surgical procedure was determined. Lytic patients were randomized to recombinant tissue plasminogen activator (rt-PA; 84 patients) or urokinase (UK; 66 patients). Recurrent ischemia, morbidity, amputation, and death rates were determined at 30 days, 6 months, and 1 year, and were analyzed on an intent-to-treat basis. RESULTS For patients randomized to lysis, a catheter was properly positioned and the lytic agent delivered in 78%. This provided a reduction in the predetermined surgical procedure in 58% of patients who had an FP occlusion and 51% of those who had an IF occlusion. rt-PA and UK were equally effective and safe, but lysis time was shorter with rt-PA (8 vs 24 hr; p < 0.05). At 1 year, the incidence of recurrent ischemia (64% vs 35%; p < 0.0001) and major amputation (10% vs 0%; p = 0.0024) was increased in patients who were randomized to lysis. Factors associated with a poor lytic outcome included FP occlusion, diabetes, and critical ischemia. No differences in mortality rates were observed at 1 year between the lysis and surgical groups. CONCLUSION Surgical revascularization for lower extremity native artery occlusions is more effective and durable than thrombolysis. Thrombolysis used initially provides a reduction in the surgical procedure for a majority of patients; however, long-term outcome is inferior, particularly for patients who have an FP occlusion, diabetes, or critical ischemia.

Evaluation of Penetrating Injuries of the Neck: Prospective Study of 223 Patients

Abstract. The objective of this study was to assess the role of clinical examination, angiography, color flow Doppler imaging, and other diagnostic tests in identifying injuries to the vascular or aerodigestive structures in patients with penetrating injuries to the neck. A prospective study was made of patients with penetrating neck injuries. All patients had a careful physical examination according to a written protocol. Stable patients underwent routine four-vessel angiography and color flow Doppler imaging. Esophagography and endoscopy were performed for proximity injuries. The sensitivity, specificity, and predictive values of physical examination, color flow Doppler studies, and other diagnostic tests were assessed during the evaluation of vascular and aerodigestive tract structures in the neck. Altogether 223 patients were entered in the study. After physical examination 176 patients underwent angiography and 99 of them underwent color flow Doppler imaging. Angiographic abnormalities were seen in 34 patients for an incidence of 19.3%, but only 14 (8.0%) required treatment. Color flow Doppler imaging was performed on 99 patients with a sensitivity of 91.7%, specificity 100%, positive predictive value (PPV) 100%, and negative predictive value (NPV) 99%. These values were all 100% when only injuries requiring treatment were considered. None of the 160 patients without clinical signs of vascular injury had serious vascular trauma requiring treatment (NPV 100%), although angiography in 127 showed 11 vascular lesions not requiring treatment. “Hard” signs on clinical examination (large expanding hematomas, severe active bleeding, shock not responding to fluids, diminished radial pulse, bruit) reliably predicted major vascular trauma requiring treatment. Among 34 of the 223 total patients (15.2%) admitted with “soft” signs, 8 had angiographically detected injuries, but only one required treatment. An esophagogram was performed on 98 patients because of proximity injuries (49 patients) or suspicious clinical signs (49 patients), and two of them showed esophageal perforations. None of the 167 patients without clinical signs of esophageal trauma had an esophageal injury requiring treatment. It was concluded that physical examination is reliable for identifying those patients with penetrating injuries of the neck who require vascular or esophageal diagnostic studies. Color flow Doppler imaging is a dependable alternative to angiography. An algorithm for the initial assessment of neck injuries is suggested.

Results of a prospective, randomized trial of surgery versus thrombolysis for occluded lower extremity bypass grafts.

PURPOSE The purpose of this study was to prospectively evaluate the treatment of patients with occluded lower extremity bypass grafts, comparing surgical revascularization with catheter-directed thrombolysis. MATERIALS AND METHODS One hundred twenty-four patients (68% male and 32% female) with lower limb bypass graft occlusion (46 autogenous and 78 prosthetic) were prospectively randomized to surgery (n = 46) or intra-arterial catheter-directed thrombolysis (n = 78) with recombinant tissue plasminogen activator (rt-PA) 0.1 mg/kg/h modified to 0.05 mg/kg/h for up to 12 hours, or urokinase (UK) 250,000 U bolus followed by 4,000 U/min for 4 hours, then 2,000 U/min for up to 36 hours. A composite clinical outcome including death, amputation, ongoing/recurrent ischemia, and major morbidity was analyzed on an intent-to-treat basis at 30 days and 1 year. RESULTS The average duration of graft occlusion was 34.0 days, with 58 (48%) presenting with acute ischemia (0 to 14 days) and 64 (52%) with chronic ischemia (> 14 days). Thirty-nine percent randomized to lysis failed catheter placement and required surgical revascularization. Overall, there was a better composite clinical outcome at 30 days (P = 0.023) and 1 year (P = 0.04) in the surgical group compared with lysis, due predominately to a reduction in ongoing/recurrent ischemia, most notable in autogenous grafts. However, following successful catheter placement, patency was restored by lysis in 84%, and 42% had a major reduction in their planned operation. One-year results of successful lysis compared favorably with the best surgical procedure, which was new graft placement. Acutely ischemic patients (0 to 14 days) randomized to lysis demonstrated a trend toward a lower major amputation rate at 30 days (P = 0.074) and significantly at 1 year (P = 0.026) compared with surgical patients, while those with > 14 days ischemia showed no difference in limb salvage but higher ongoing/recurrent ischemia in lytic patients (P < 0.001). Patients with occluded prosthetic grafts had greater major morbidity than did those with occluded autogenous grafts (P < 0.02). CONCLUSIONS Proper catheter positioning currently limits the potential of catheter-directed thrombolysis for lower extremity bypass graft occlusion. Patients with graft occlusion > 14 days have a significantly better outcome when treated surgically, with a new bypass being the best surgical option. However, in patients with acute limb ischemia (< 14 days) successful thrombolysis of occluded lower extremity bypass grafts improves limb salvage and reduces the magnitude of the planned surgical procedure. Patients with occluded prosthetic grafts suffer more major morbid events compared with occluded autogenous grafts.

Patterns of treatment for peripheral arterial disease in the United States: 1996-2005

OBJECTIVE Endovascular procedures are increasingly used in the treatment of peripheral arterial disease (PAD). Whether this new procedural approach translates to clinical outcomes equivalent or superior to open surgical revascularization is a subject of debate. We sought to analyze population-based rates of major amputations for PAD during a time period in which the use of endovascular surgical procedures increased dramatically. METHODS We used the 1996-2005 Nationwide Inpatient Sample (NIS) to analyze rates of amputations and vascular interventions, and also to characterize the treatment of patients admitted acutely for PAD. Vascular interventions were designated based on International Classification of Diseases (ICD) procedure codes as open bypass, endovascular intervention, or major amputation (disarticulation at ankle or higher amputation). Population-based age-adjusted incidence rates of treatment were calculated by combining procedure rates with census data. RESULTS Our analysis included 97,000 acute admissions for PAD, 83,000 major amputations, 77,500 endovascular procedures, and 171,000 open vascular bypass operations. Between 1996 and 2005, population-based rates of acute admissions for PAD decreased by 4.3% per year, open procedures by 6.6% per year, and major amputations by 6.4% per year, whereas endovascular procedures increased by 4.8% per year. Of patients acutely admitted for PAD, the likelihood of undergoing an amputation decreased (30.2% to 21.8%), the likelihood of undergoing an open vascular procedure decreased (34.5% to 26.3%), and the likelihood of undergoing an endovascular operation increased (12.7% to 28.3%). All of these changes were statistically significant at P < .05. CONCLUSION The last decade has seen a significant increase in the use of endovascular procedures and a decrease in rates of major amputation. These trends are seen both for patients admitted with acute PAD, as well as in the population in general. While our study was not designed to demonstrate a causal relationship, our findings suggest an association between increased application of endovascular technology and reduced rates of amputation in patients with PAD.

Health-Related Quality of Life after Carotid Stenting versus Carotid Endarterectomy: Results from CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial)

OBJECTIVES The purpose of this study was to compare health-related quality of life (HRQOL) outcomes in patients treated with carotid artery stenting (CAS) versus carotid endarterectomy (CEA). BACKGROUND In CREST (Carotid Revascularization Endarterectomy versus Stenting Trial), the largest randomized trial of carotid revascularization to date, there was no significant difference in the primary composite endpoint, but rates of stroke and myocardial infarction (MI) differed between CAS and CEA. To help guide individualized clinical decision making, we compared HRQOL among patients enrolled in the CREST study. We also performed exploratory analyses to evaluate the association between periprocedural complications and HRQOL. METHODS We measured HRQOL at baseline, and after 2 weeks, 1 month, and 1 year among 2,502 patients randomly assigned to either CAS or CEA in the CREST study. The HRQOL was assessed using the Medical Outcomes Study Short-Form 36 (SF-36) and 6 disease-specific scales designed to study HRQOL in patients undergoing carotid revascularization. RESULTS At both 2 weeks and 1 month, CAS patients had better outcomes for multiple components of the SF-36, with large differences for role physical function, pain, and the physical component summary scale (all p < 0.01). On the disease-specific scales, CAS patients reported less difficulty with driving, eating/swallowing, neck pain, and headaches but more difficulty with walking and leg pain (all p < 0.05). However, by 1 year, there were no differences in any HRQOL measure between CAS and CEA. In the exploratory analyses, periprocedural stroke was associated with poorer 1-year HRQOL across all SF-36 domains, but periprocedural MI or cranial nerve palsy were not. CONCLUSIONS Among patients undergoing carotid revascularization, CAS is associated with better HRQOL during the early recovery period as compared with CEA-particularly with regard to physical limitations and pain-but these differences diminish over time and are not evident after 1 year. Although CAS and CEA are associated with similar overall HRQOL at 1 year, event-specific analyses confirm that stroke has a greater and more sustained impact on HRQOL than MI. (Carotid Revascularization Endarterectomy versus Stenting Trial [CREST]; NCT00004732)

Blunt popliteal artery trauma: One hundred consecutive injuries

An institutional experience with 100 consecutive blunt popliteal artery injuries over a 20-year period was reviewed. The overall amputation rate was 15%; however, during the past 7 years this has declined from 23% to 6%. Minimizing delay in the revascularization of ischemic limbs, routine systemic heparinization, primary arterial repair when possible, repair of popliteal venous injuries, aggressive wound debridement, and early soft tissue coverage have contributed to improved limb salvage during the 1980s.

Preferential Induction of EphB4 over EphB2 and Its Implication in Colorectal Cancer Progression

The receptor tyrosine kinase EphB2 is expressed by colon progenitor cells; however, only 39% of colorectal tumors express EphB2 and expression levels decline with disease progression. Conversely, EphB4 is absent in normal colon but is expressed in all 102 colorectal cancer specimens analyzed, and its expression level correlates with higher tumor stage and grade. Both EphB4 and EphB2 are regulated by the Wnt pathway, the activation of which is critically required for the progression of colorectal cancer. Differential usage of transcriptional coactivator cyclic AMP-responsive element binding protein-binding protein (CBP) over p300 by the Wnt/beta-catenin pathway is known to suppress differentiation and increase proliferation. We show that the beta-catenin-CBP complex induces EphB4 and represses EphB2, in contrast to the beta-catenin-p300 complex. Gain of EphB4 provides survival advantage to tumor cells and resistance to innate tumor necrosis factor-related apoptosis-inducing ligand-mediated cell death. Knockdown of EphB4 inhibits tumor growth and metastases. Our work is the first to show that EphB4 is preferentially induced in colorectal cancer, in contrast to EphB2, whereby tumor cells acquire a survival advantage.

Surgical procedures in the management of Takayasu's arteritis

Takayasus arteritis is an inflammatory arteriopathy that often progresses to obliteration of multiple large arteries. Variable results have been reported after medical and surgical management. Twenty female patients with Takayasus arteritis were treated from 1973 to 1989. Eleven (55%) patients had hypertension. Upper or lower extremity ischemia was present in 12 (60%) patients and cerebrovascular insufficiency in seven (35%). Nine patients initially managed with corticosteroids had no improvement in signs or symptoms of arterial insufficiency. Eleven patients had 16 vascular procedures for the following indications: renovascular hypertension (6), extremity ischemia (5), cerebrovascular insufficiency (2), dilation ascending aorta with aortic insufficiency (1), thoracic aortic aneurysm (1), abdominal aortic aneurysm (1). Procedures included aortorenal bypass (5), carotid-subclavian, axillary, or brachial bypass (4), aorto-carotid bypass (2), aneurysm resection (2), supra-celiac aorto-femoral bypass (1), ascending aorta/aortic valve replacement (1), and nephrectomy (1). Clinical improvement occurred in all patients. There were no operative deaths. All are alive at a mean follow-up of 5.75 years (6 months to 16 years). Revision of the initial reconstruction has been required for recurrent renovascular hypertension in one patient and extremity ischemia in another. The other nine patients remain symptomatically improved. Symptomatic Takayasus arteritis frequently requires arterial reconstruction. Symptomatic improvement and excellent long-term graft patency can be expected after arterial reconstruction.

Role of routine arteriography in blunt lower-extremity trauma.

During an 18-month period, 53 patients with unilateral blunt lower-extremity trauma were entered into a prospective study designed to determine how often clinically occult arterial injuries are identified by routine arteriography, and how often these injuries are of sufficient magnitude to warrant therapeutic intervention. Patients underwent diagnostic arteriography if one or more of the following abnormal clinical findings were present: distal pulse deficit, nerve deficit, soft-tissue loss, decreased capillary refill, bruit, or a history of hemorrhage or hypotension. In the absence of these findings, arteriography was performed for significant orthopedic injuries, i.e., knee dislocations or complex long-bone fractures. In 31 patients (58%), arteriography was performed because 1 or more abnormal clinical findings were present and 12 arterial injuries were identified, 4 requiring arterial repair. The presence of a knee dislocation or complex long-bone fracture was the only indication for arteriography in 22 patients (42%) and 3 arterial injuries were identified, none requiring operative intervention. For all patients, two variables, pulse deficit and delayed capillary refill, strongly correlated (p less than 0.05) with arteriographic demonstration of an arterial injury. In the absence of these findings, routine diagnostic arteriography will have a low diagnostic yield and will rarely identify a vascular injury in a major artery that will require operative repair. Arteriography should be selectively performed and guided by examination and noninvasive Doppler indices.

Chronic Baroreflex Activation: A Potential Therapeutic Approach to Heart Failure With Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) is a substantial public health issue, equal in magnitude to heart failure with reduced ejection fraction. Clinical outcomes of HFpEF patients are generally poor, related annual accrual of health care expenses amount to billions of dollars, and no therapy has been shown to be effective in randomized clinical trials. Baroreflex activation therapy (BAT) produced by stimulating the carotid sinuses using an implanted device (Rheos) is being studied for the treatment of hypertension, the primary comorbidity of HFpEF. Other potential benefits include regression of left ventricular hypertrophy, normalization of the sympathovagal balance, inhibition of the renin-angiotensin-aldosterone system, arterio- and venodilation, and preservation of renal function. This paper reviews the evidence suggesting that BAT may be a promising therapy for HFpEF and introduces the HOPE4HF trial (ClinicalTrials.gov Identifier: NCT00957073), a randomized outcomes trial designed to evaluate the clinical safety and efficacy of BAT in the HFpEF population.