Sukgu M. Han

Efficacy and safety of alfimeprase in patients with acute peripheral arterial occlusion (PAO)

PURPOSE To investigate the safety and effectiveness of a novel thrombolytic, alfimeprase, in catheter-directed thrombolysis (CDT) of acute peripheral arterial occlusions (PAO). METHODS Between April 2005 and March 2007, patients with acute PAO (Rutherford class I or IIa) of a lower extremity and onset of symptoms within 14 days prior to randomization were included. Studies HA004 and HA007 enrolled respectively 300 and 102 patients. Both studies HA004 and HA007 were placebo-controlled. HA004 had two placebo arms, intrathrombus and perithrombus, while HA007 had intrathrombus placebo arm. HA004 was partially double-blind (perithrombus group was not blinded) and HA007 was double-blind. Patients were randomized to intrathrombus alfimeprase (0.3 mg/kg), intrathrombus (IT) placebo, or perithrombus (PT) placebo (HA004 only) in two divided weight-based infusions 2 hours apart. Depending on arteriographic results after treatment, patients received no further intervention or underwent endovascular therapy or open vascular surgery. The primary endpoint of both studies was efficacy of alfimeprase compared with placebo as measured by avoidance of an open vascular surgery procedure at 30 days. RESULTS The avoidance of open vascular surgery at 30 days was seen in 52 (34.9%), 42 (37.2%), and 7 patients (18.4%) with alfimeprase, IT placebo, and PT placebo in HA004 and 15 (29.4%) and 9 patients (17.6%) with alfimeprase and IT placebo in HA007; differences between alfimeprase and IT placebo were not statistically significant. Results were similar for secondary endpoints, including arterial flow restoration in 4 hours, 30-day ankle-brachial index, index limb pain severity, and hospital stay duration. The overall rate of adverse events was higher with alfimeprase than placebo. Hemorrhagic and peripheral embolic event rates with alfimeprase were 23% (34 patients) and 10.1% (15 patients) in HA004 and 9.4% (5 patients) and 9.8% (5 patients) in HA007; rates with IT placebo were 11% (12 patients, P = .107) and 5% (5 patients, P = .148) in HA004 and 10% (5 patients, P = .982) and 0% in HA007 (P = .07). No deaths were related to study drug administration. CONCLUSIONS CDT for acute PAO with alfimeprase was as safe as placebo. However, alfimeprase was no more effective than placebo in increasing 30-day surgery-free survival. The surprising effectiveness of placebo alone demonstrates that the inclusion of a placebo arm is essential to the design of future lytic trials.

Ultrasound-determined diameter measurements are more accurate than axial computed tomography after endovascular aortic aneurysm repair

OBJECTIVE This study evaluated the correlation of ultrasound (US)-derived aortic aneurysm diameter measurements with centerline, three-dimensional (3-D) reconstruction computed tomography (CT) measurements after endovascular aortic aneurysm repair (EVAR). METHODS Concurrent CT and US examinations from 82 patients undergoing post-EVAR surveillance were reviewed. The aortic aneurysm diameter was defined as the major axis on the centerline images of 3-D CT reconstruction. This was compared with US-derived minor and major axis measurements, as well as with the minor axis measurement on the conventional axial CT images. Correlation was evaluated with linear regression analyses. Agreement between different imaging modalities and measurements was assessed with Bland-Altman plots. RESULTS The correlation coefficients from linear regression analyses were 0.92 between CT centerline major and US minor measurements, 0.94 between CT centerline major and US major measurements, and 0.93 between CT minor and centerline major measurements. Bland-Altman plots showed a mean difference of 0.11 mm between US major and CT centerline measurements compared with 5.38 mm between US minor and CT centerline measurements, and 4.25 mm between axial CT minor and centerline measurements. This suggested that, compared with axial CT and US minor axis measurements, US major axis measurements were in better agreement with CT centerline measurements. Variability between major and minor US and CT centerline diameter measurements was high (standard deviation of difference, 4.27-4.84 mm). However, high variability was also observed between axial CT measurements and centerline CT measurements (standard deviation of difference, 4.36 mm). CONCLUSIONS The major axis aneurysm diameter measurement obtained by US imaging for surveillance after EVAR correlates well and is in better agreement with centerline 3-D CT reconstruction diameters than axial CT.

Risk Factors for 30-Day Hospital Readmission in Patients Undergoing Treatment for Peripheral Artery Disease.

Early hospital readmission among vascular surgery patients is a focus of Medicare’s new reimbursement structure. We aim to identify factors associated with 30-day readmission after lower extremity interventions to treat peripheral artery disease (PAD). Retrospective analysis of 174 consecutive patients discharged from the vascular surgery service between January 1, 2011, and July 31, 2012, after procedures for lower extremity PAD was performed. Of 174 patients, 37 were readmitted within 30 days of discharge. There were no significant differences in baseline characteristics between the readmitted and the nonreadmitted groups. In a multivariate logistic regression model, urgent operation and advanced chronic kidney disease (CKD) were associated with increased risk of 30-day readmission. The most common reasons for readmission were infection of the surgical site or index limb (18 of 37), followed by unresolved limb symptoms (13 of 37). The 30-day readmission is frequent after lower extremity interventions to treat PAD. Urgent operative intervention and advanced CKD appear to be risk factors for early hospital readmission.

Design and in vitro evaluation of a real-time catheter localization system using time of flight measurements from seven 3.5 MHz single element ultrasound transducers towards abdominal aortic aneurysm procedures

Interventional surgical instrument localization is a crucial component of minimally invasive surgery. Image guided surgery researchers are investigating devices broadly categorized as surgical localizers to provide real-time information on the instruments 3D location and orientation only. This paper describes the implementation and in vitro evaluation of a prototype real-time nonimaging ultrasound-based catheter localizer system towards use in abdominal aortic aneurysm procedures. The catheter-tip is equipped with a single element ultrasound transducer which is tracked with an array of seven external single element transducers. The performance of the system was evaluated in a water tank and additionally in the presence of pork belly tissue and also a nitinol-dacron stent graft. The mean root mean square errors were respectively 1.94±0.06, 2.54±0.31 and 3.33±0.06 mm. In addition, this paper illustrates errors induced by transducer aperture size and suggests a method for aperture error compensation. Aperture compensation applied to the same experimental data yielded mean root mean square errors of 1.05±0.07, 2.42±0.33 and 3.23±0.07mm respectively for water; water and pork; and water, pork and stent experiments. Lastly, this paper presents a video showing free-hand movement of the catheter within the water tank with data capture at 25 frames per second.

The influence of stents on the performance of an ultrasonic navigation system for endovascular procedures

OBJECTIVE Image-guided surgery provides a mechanism to accurately and quickly assess the location of surgical tools relative to a preoperative image. Traditional image-guided surgery relies on infrared or radiofrequency triangulation to determine an instrument location relative to a preoperative image and has been primarily used in head and neck procedures. Advances in ultrasonic tracking devices, designed for tracking catheters within vessels, may provide an opportunity for image-guided endovascular procedures. This study evaluates the positional accuracy of an ultrasonic navigation system for tracking an endovascular catheter when different stents and graft materials have been deployed in an in vitro system. METHODS Stent and graft materials commonly used in endovascular procedures were used for this study in combination with a custom three-head ultrasonic transducer navigation system. The stents evaluated were composed of Dacron/nitinol, polytetrafluoroethylene (PTFE)/nitinol, and bare nitinol. They were deployed into excised porcine tissue cannulized with a rotary drill, and a catheter with a custom microtransducer probe was inserted. The distance from each ultrasonic tracking module to a probe mounted on an endovascular catheter was measured using time of flight techniques, and the catheter position in three-dimensions was calculated using triangulation. RESULTS The measured position was compared to the actual catheter position determined by a precision translation stage. The PTFE/nitinol, bare nitinol, and Dacron/nitinol stent materials were evaluated and resulted in a maximum error of 1.7, 3.0, and 3.6 mm and an SD of 0.7, 1.2, and 1.4 mm, respectively. A reduction in signal intensity of up to 6x was observed during passage of the endovascular probe through the stent materials, but no reduction in the accuracy of the ultrasonic navigation system was evident. CONCLUSION The use of an ultrasonic-based navigation system is feasible in endovascular procedures, even in the presence of common stent materials. It may have promise as a navigational tool for endovascular procedures.

Development of a Flexible Implantable Sensor for Postoperative Monitoring of Blood Flow

We have developed a blood flow measurement system using Doppler ultrasound flow sensors fabricated of thin and flexible piezoelectric‐polymer films. These flow sensors can be wrapped around a blood vessel and accurately measure flow. The innovation that makes this flow sensor possible is the diffraction‐grating transducer. A conventional transducer produces a sound beam perpendicular to its face; therefore, when placed on the wall of a blood vessel, the Doppler shift in the backscattered ultrasound from blood theoretically would be 0. The diffraction‐grating transducer produces a beam at a known angle to its face; therefore, backscattered ultrasound from the vessel will contain a Doppler signal. Flow sensors were fabricated by spin coating a poly(vinylidene fluoride–trifluoroethylene) copolymer film onto a flexible substrate with patterned gold electrodes. Custom‐designed battery‐operated continuous wave Doppler electronics along with a laptop computer completed the system. A prototype flow sensor was evaluated experimentally by measuring blood flow in a flow phantom and the infrarenal aorta of an adult New Zealand White rabbit. The flow phantom experiment demonstrated that the error in average velocity and volume blood flow was less than 6% for 30 measurements taken over a 2.5‐hour period. The peak blood velocity through the rabbit infrarenal aorta measured by the flow sensor was 118 cm/s, within 1.7% of the measurement obtained using a duplex ultrasound system. The flow sensor and electronics operated continuously during the course of the 5‐hour experiment after the incision on the animal was closed.

Reversible cerebral vasoconstriction syndrome is a rare cause of stroke after carotid endarterectomy

Neurologic events after carotid endarterectomy (CEA) require prompt diagnosis and management to avoid potentially catastrophic sequelae. This report describes a 69-year-old gentleman who underwent a left CEA for a high-grade asymptomatic carotid stenosis with concomitant contralateral carotid occlusion. He had transient and crescendo neurologic events in the first 3 postoperative weeks that culminated in right hand weakness and paresthesia, despite dual antiplatelet therapy, maximal anticoagulation, and undergoing stenting of the endarterectomy site. Neurologic events recurred despite these measures and subsequent angiography showed reversible cerebral vasoconstriction syndrome that was successfully managed without further events. Reversible cerebral vasoconstriction syndrome is an unusual but important cause of neurologic events after CEA that requires aggressive and directed medical therapy.

Time of flight and FMCW catheter localization

This work uses ultrasound signals to track the 3D location of a catheter. Our system provides 3D coordinate data and not images. The coordinates can be registered with preoperative, 3D CT image data to provide a “GPS” like navigation system for catheter based minimally invasive surgery. We used three ultrasound piston transducers as transmitters and held these transmitters at fixed locations. We then moved a custom catheter based transducer within the transmitted ultrasound field. Time of flight (TOF) or frequency modulated continuous wave (FMCW) range-finding measured the distance between each transmitting transducer and the catheter. We used trilateration to calculate 3D coordinates for the catheter given the spatial coordinates of the transmitters. We performed the localization procedure in a DI water tank and a porcine tissue phantom. In the tank experiment, we shifted the catheter in 1 mm increments for two 10 cm runs, once towards the plane of the transmitters (axially) and once parallel to the plane of the transmitters (laterally). We evaluated performance with linear regression. For TOF, the slope and linear regression fits were m =0.976 with Spearman correlation coefficient Rs = 0.993 and m=0.709 with Rs = 1 for the axial and lateral translation coordinates, respectively. For FMCW, the values were m = 1.004 with Rs = 1 and m= 0.928 with Rs = 0.996, all statistically significant with p ≪0.001. We prepared the porcine tissue phantom by implanting a model silicone aorta beneath the skin surface and imaged it with a CT scan. We advanced the catheter laterally into the phantom and used TOF range-finding to track the position. We then plotted the coordinates on the CT images (Fig. 1). Despite crude registration methods, results demonstrated agreement between the anatomical environment and the tracked path.

A flexible implantable sensor for post‐operative monitoring of blood flow.

A blood flow measurement system utilizing flexible ultrasonic Doppler patch‐sensors and battery operated electronics was developed. These sensors can be wrapped around a blood vessel to safely and accurately measure flow. Prototype sensors were fabricated by spin‐coating 12‐μm‐thick P(VDF‐TrFE) films onto 25‐μm‐thick flexible polyimide substrates with patterned gold electrodes. The transmitting electrodes consisted of an array of equally spaced traces. Oppositely oriented electric fields were applied to alternate traces during polarizing so that when the traces are excited by a 40‐MHz sinusoidal signal, the P(VDF‐TrFE) film produces successive positive and negative pressure waves that sum to form two diffraction‐grating beams at 39 deg with respect to blood flow. A uniform electrode for a receiving transducer was positioned to maximize the reception of the backscattered Doppler signal from the center of a 3‐mm‐diameter blood vessel. Patch‐sensors were placed around the abdominal aorta of a New Zealand whi...

Management of patients with acute aortic syndrome through a regional rapid transport system

Objective: The objective of this study was to describe the outcomes of patients with acute aortic syndrome (AAS) during and after transfer to a regional aortic center by a rapid transport system. Methods: Review of patients with AAS who were transferred by a rapid transport system to a regional aortic center was performed. Data regarding demographics, diagnosis, comorbidities, transportation, and hospital course were acquired. Severity of existing comorbidities was determined by the Society for Vascular Surgery Comorbidity Severity Score (SVSCSS). The Acute Physiology and Chronic Health Evaluation II (APACHE II) score assessed physiologic instability on admission. Risk factors associated with system‐related (transfer and hospital) mortality were identified by univariate and multivariate linear regression analysis. Results: During a recent 18‐month period (December 2013‐July 2015), 183 patients were transferred by a rapid transport system; 148 (81%) patients were transported by ground and 35 (19%) by air. Median distance traveled was 24 miles (range, 3.6‐316 miles); median transport time was 42 minutes (range, 10‐144 minutes). Two patients died during transport, one with a type A dissection, the other of a ruptured abdominal aortic aneurysm. There were 118 (66%) patients who received operative intervention. Median time to operation was 6 hours. Type B dissections had the longest median time to operation, 45 hours, with system‐related mortality of 1.9%; type A dissections had the shortest median time, 3 hours, and a system‐related mortality of 16%. Overall, system‐related mortality was 15%. On univariate analysis, factors associated with system‐related mortality were age ≥65 years (P = .026), coronary artery disease (P = .030), prior myocardial infarction (P = .049), prior coronary revascularization (P = .002), SVSCSS of >8 (P < .001), abdominal pain (P = .002), systolic blood pressure <90 mm Hg at sending hospital (P = .001), diagnosis of aortic aneurysm (P = .013), systolic blood pressure <90 mm Hg in the intensive care unit (P < .001), and APACHE II score >10 (P = .004). Distance traveled and transport mode and duration were not associated with increased risk of system‐related mortality. Only SVSCSS of >8 (odds ratio, 7.73; 95% confidence interval, 2.32‐25.8; P = .001) was independently associated with an increase in system‐related mortality on multivariate analysis. Conclusions: Implementation of a rapid transport system, regardless of mode or distance, can facilitate effective transfer of patients with AAS to a regional aortic center. An SVSCSS of >8 predicted an increased system‐related mortality and may be a useful metric to assess the appropriateness of patient transfer.