Michael T. Caps

Prospective Study of Atherosclerotic Disease Progression in the Renal Artery

BACKGROUND The aim of this study was to determine the incidence of and the risk factors associated with progression of renal artery disease in individuals with atherosclerotic renal artery stenosis (ARAS). METHODS AND RESULTS Subjects with >/=1 ARAS were monitored with serial renal artery duplex scans. A total of 295 kidneys in 170 patients were monitored for a mean of 33 months. Overall, the cumulative incidence of ARAS progression was 35% at 3 years and 51% at 5 years. The 3-year cumulative incidence of renal artery disease progression stratified by baseline disease classification was 18%, 28%, and 49% for renal arteries initially classified as normal, <60% stenosis, and >/=60% stenosis, respectively (P=0.03, log-rank test). There were only 9 renal artery occlusions during the study, all of which occurred in renal arteries having >/=60% stenosis at the examination before the detection of occlusion. A stepwise Cox proportional hazards model included 4 baseline factors that were significantly associated with the risk of renal artery disease progression during follow-up: systolic blood pressure >/=160 mm Hg (relative risk [RR]=2.1; 95% CI, 1.2 to 3.5), diabetes mellitus (RR=2.0; 95% CI, 1.2 to 3.3), and high-grade (>60% stenosis or occlusion) disease in either the ipsilateral (RR=1.9; 95% CI, 1.2 to 3.0) or contralateral (RR=1.7; 95% CI, 1.0 to 2.8) renal artery. CONCLUSIONS Although renal artery disease progression is a frequent occurrence, progression to total renal artery occlusion is not. The risk of renal artery disease progression is highest among individuals with preexisting high-grade stenosis in either renal artery, elevated systolic blood pressure, and diabetes mellitus.

Hemostasis of punctured blood vessels using high-intensity focused ultrasound

The hemorrhagic complications of vascular injury can be significant. We report on the use of high-intensity focused ultrasound (HIFU) to stop the hemorrhage of punctured blood vessels in pigs. Two HIFU transducers with frequencies of 3.5 and 2.0 MHz, each equipped with a water-filled conical housing, were used. Major blood vessels (femoral artery and vein, axillary artery, carotid artery and jugular vein), 2-10 mm in diameter, of anesthetized pigs were exposed surgically and punctured with 14- and 18-gauge needles to produce moderate to profuse bleeding. Complete hemostasis was achieved in less than 3 min of HIFU treatment in most blood vessels, and all vessels were patent after the treatment. Both HIFU frequencies were effective in producing hemostasis. Gross examination of the HIFU-treated vessels showed a consistent hardening of the soft tissue surrounding the blood vessels, providing a seal for the puncture hole. Microscopic examination of the vessels showed a remarkably localized HIFU treatment, resulting in coagulation of the adventitia, and an extensive fibrin network around the vessels and in the puncture hole. The vessel walls exhibited focal swelling, without evidence of irreversible injury. HIFU may provide a useful method for achieving hemostasis of punctured and traumatized blood vessels in a variety of clinical settings.

Determinants of chronic venous disease after acute deep venous thrombosis

PURPOSE The purpose of this investigation was to evaluate the relationship between the presenting features of an acute deep venous thrombosis (DVT), the subsequent natural history of the thrombus, and the ultimate outcome as defined according to the Society for Vascular Surgery and the North American Chapter of the International Society for Cardiovascular Surgery reporting standards in venous disease. METHODS Patients with an acute DVT were followed with serial clinical and ultrasound examinations. Thrombus extent within 7 venous segments was scored retrospectively according to the reporting standards (scores ranged from 0 to 3), and segmental reflux was scored as present (1) or not present (0). The initial and final thrombus scores, the rates of recanalization and rethrombosis, and the total reflux scores were then calculated from these grading scales and related to ultimate chronic venous disease (CVD) classification. RESULTS Sixty-eight patients with an acute DVT in 73 limbs were followed for 18 to 110 months (mean, 55 +/- 26 months). At the completion of the follow-up period, 20 extremities (27%) were asymptomatic (class 0), 13 (18%) had pain or prominent superficial veins (class 1), 25 (34%) had manifested edema (class 3), 13 (18%) had developed hyperpigmentation (class 4), and 2 (3%) had developed ulceration (class 5). In a univariate analysis, CVD classification was correlated with the reflux score (P =.003) but not with the initial or final thrombus score or with the rate of recanalization or rethrombosis. In a multivariate model of features documented at presentation, only the tibial thrombosis score was a significant predictor of CVD classification (R2 =.06). Outcome was better predicted (R2 =.29) with a model that included variables defined during follow-up the final reflux score, the final popliteal score, and the rate of recanalization. CONCLUSION The ability to predict the severity of CVD after an acute DVT is currently limited, although the natural history appears more important than the presenting features of the event. The extent of reflux, the presence of persistent popliteal obstruction, and the rate of recanalization are related to ultimate CVD classification, but other determinants remain to be identified.

Propagation, rethrombosis and new thrombus formation after acute deep venous thrombosis

PURPOSE The purpose of this study was to determine the incidence, timing, and outcome of further thrombotic events after an initial episode of acute deep venous thrombosis. METHODS Venous thrombi in 204 lower extremities (177 patients) were monitored with duplex ultrasonography at intervals of 1 day, 7 days, 1 month, every 3 months for 1 year, and yearly thereafter. RESULTS Among initially involved extremities, propagation to new segments occurred in 61 (30%) and rethrombosis occurred in 63 (31%). Both propagation and rethrombosis, in different segments, occurred in 27 (13%) extremities. New thrombi were also noted in nine (6%) initially uninvolved extremities. These events were not associated with identifiable clinical risk factors, although extremities with rethrombosis were more extensively involved at presentation. Propagation in initially involved extremities was an early event, occurring within a median of 40 days in all segments. New thrombotic events in initially uninvolved extremities and rethrombosis occurred as later events. The development of reflux was significantly more common among all initially uninvolved segments to which thrombus extended and among mid and distal superficial femoral and popliteal artery segments with rethrombosis. CONCLUSIONS Recurrent thrombotic events are common after acute deep venous thrombosis and adversely affect the ultimate development of valvular incompetence. Their occurrence is unrelated to recognized clinical risk factors and can occur despite standard anticoagulation measures.

Use of high-intensity focused ultrasound to control bleeding

OBJECTIVE High-intensity focused ultrasound (HIFU) has been shown to be effective in controlling hemorrhage from punctures in blood vessels. The objective of the current study was to investigate the capability of HIFU to stop bleeding after a more severe type of vascular injury, namely longitudinal incisions of arteries and veins. METHODS The superficial femoral arteries, common femoral arteries, carotid arteries, and jugular veins of four anesthetized pigs were exposed surgically. A longitudinal incision, 2 to 8 mm in length, was produced in the vessel. HIFU treatment was applied within 5 seconds of the onset of the bleeding. The HIFU probe consisted of a high-power, 3.5-MHz, piezoelectric transducer with an ellipsoidal focal spot that was 1 mm in cross section and 9 mm in axial dimension. The entire incision area was scanned with the HIFU beam at a rate of 15 to 25 times/second and a linear displacement of 5 to 10 mm. A total of 76 incisions and HIFU treatments were performed. RESULTS Control of bleeding (major hemosatsis) was achieved in all 76 treatments, with complete hemostasis achieved in 69 treatments (91%). The average treatment times of major and complete hemostasis were 17 and 25 seconds, respectively. After the treatment, 74% of the vessels in which complete hemostasis was achieved were patent with distal blood flow and 26% were occluded. The HIFU-treated vessels showed a consistent coagulation of the adventitia surrounding the vessels, with a remarkably localized injury to the vessel wall. Extensive fibrin deposition at the treatment site was observed. CONCLUSION HIFU may provide a useful method of achieving hemostasis for arteries and veins in a variety of clinical applications.

Early outcome after isolated calf vein thrombosis.

PURPOSE The clinical significance of isolated calf vein thrombosis (CVT), particularly with respect to development of the postthrombotic syndrome, remains controversial. The purpose of this study was to define the early natural history of CVT in relation to persistent lower extremity symptoms, propagation, recanalization, and the development of valvular incompetence. METHODS Over a 116-month period, 499 patients with acute deep venous thrombosis (DVT) were referred to our research laboratory, of whom 58 (12%) had thrombosis confined to the calf veins of at least one extremity. The lower extremities of 268 patients (29 with isolated CVT) were followed-up clinically and with duplex ultrasonography at intervals of 1 day, 7 days, 1 month, every 3 months for the first year, and yearly thereafter. RESULTS Seventy percent of extremities with CVT were symptomatic at presentation. Although the prevalence of clinical signs and symptoms decreased to 29% by 1 month, 23% of patients had persistent pain, edema, or both at 12 months. In contrast, 9% of uninvolved extremities contralateral to a CVT and 54% of extremities with proximal DVT remained symptomatic at 1 year (p = 0.004). Recanalization proceeded rapidly such that the mean thrombus load was reduced by 50% at 1 month and to zero at 1 year. The prevalence of valvular incompetence progressively increased such that reflux was present in 24% of extremities at 1 year. Although its investigation was not a primary goal of this study, pulmonary embolism was diagnosed at presentation and during follow-up in 11% and 3% of patients, respectively. CONCLUSIONS The natural history of CVT is complicated by persistent symptoms and the development of valvular incompetence in approximately one-quarter of patients. This potential for persistent lower extremity symptoms should be considered in evaluating the clinical relevance of isolated calf vein DVT.

Vein graft lesions: Time of onset and rate of progression

PURPOSE The objectives of this study were to determine the time of onset, location, severity, rate of progression, and subsequent fate of infrainguinal vein graft lesions. METHODS Sixty-one infrainguinal vein grafts were studied serially with duplex ultrasonography to document the location and severity of each lesion. Grafts were studied at 1, 2, 3, 4, 6, 9, 12, and 18 months and then annually. RESULTS The cumulative secondary graft patency rate at 3 years (life-table analysis) was 93.2%. A total of 158 lesions were detected in 55 of the 61 grafts studied. The degree of diameter reduction at the time of initial detection was as follows: 1% to 19% (29.6%), 20% to 49% (51.0%), 50% to 75% (17.3%), and greater than 75% (3.1%). Forty-eight percent were detected at the first examination, 59.2% within 2 months, and 85.7% within 6 months. Progression was detected in 31.2% of the lesions by 6 and in 39.1% of the lesions by 18 months (life-table analysis). Thrombosis, in the absence of significant changes in ankle-brachial index (> or = 0.15) or return of symptoms, was not observed in grafts that had lesions with less than 75% diameter reduction. CONCLUSIONS The data support the performance of a duplex scan either during surgery or before discharge from the hospital in addition to frequent surveillance for the first 6 months. Frequent surveillance is appropriate for lesions with less than 75% diameter reduction as long as they remain asymptomatic and without a significant reduction in the ankle-brachial index.

Venous valvular reflux in veins not involved at the time of acute deep vein thrombosis

PURPOSE The aim of this study was to determine whether, in lower extremities with documented episodes of acute deep venous thrombosis (DVT), incompetence develops in veins that were not the site of thrombosis. METHODS Patients were monitored with serial duplex ultrasonography at 1 day, 1 week, 1, 3, 6, 9, and 12 months, and then annually after detection of acute DVT. The following venous segments were analyzed: common femoral, greater saphenous, proximal superficial femoral, deep femoral, popliteal, and posterior tibial. The incidence of reflux development in both thrombosed and uninvolved segments was determined. Reflux was categorized as either transient or permanent. RESULTS A total of 227 limbs in 188 patients were serially studied. Mean follow-up was 19.9 months (range 1 to 88 months). Overall, 403 of the 1423 segments (28.3% +/- 2.3%) developed reflux during the study, of which 118 (29.3% +/- 4.4%) had no prior or concurrent history of thrombosis. Considering only the segments that developed incompetence, the percent without prior thrombosis at each level was as follows: common femoral vein (40.0%), greater saphenous vein (53.1%), deep femoral vein (20.6%), proximal superficial femoral vein (23.9%), popliteal vein (8.9%), and posterior tibial vein (31.9%). Valvular insufficiency developing in segments uninvolved with thrombus was more likely to be transient (40.2%) than was the reflux in thrombosed segments (22.6%). This difference was statistically significant (p < 0.05). CONCLUSIONS Permanent venous valvular damage can occur in the absence of thrombosis after DVT. Reflux in uninvolved venous segments has a different anatomic distribution and is more likely to be transient than the incompetence associated with thrombosis.

Hemostasis of punctured vessels using Doppler-guided high-intensity ultrasound.

The use of Doppler ultrasound was investigated to determine if it would aid in guiding the application of high-intensity focused ultrasound (HIFU) to stop bleeding from punctured vessels. Major vessels (abdominal aorta, illiac, carotid, common femoral and superficial femoral arteries and the jugular vein) were surgically exposed, punctured and treated in anesthetized pigs. Treatment was applied when the Doppler sounds indicated the focus coincided with the bleeding site. In 89 treatment trials, the average time to achieve major hemostasis (a point where bleeding was reduced to a level of only oozing) was 8 s, and for complete hemostasis was 13 s. These times were significantly shorter than those of an identical former study in which only visual guidance was used. In that study, the average times for major and complete hemostasis were 40 and 62 s, respectively. The advantage of Doppler guidance in applying HIFU in treating bleeding vessels was demonstrated.

Control of splenic bleeding by using high intensity ultrasound.

BACKGROUND High-intensity focused ultrasound (HIFU) has been shown to control bleeding from liver incisions, and blood vessel punctures and incisions. The objective of the current study was to investigate the capability of HIFU to stop bleeding from splenic injuries in a pig model. METHODS Surgical incisions, 25 to 50 mm in length and 2 to 8 mm in depth, were made in the spleens of five anesthetized pigs. HIFU with a frequency of 5 MHz was applied within 5 seconds of making the incision. A total of 39 incisions and HIFU treatments were performed. RESULTS Bleeding from all incisions was stopped completely after HIFU treatment. The average times to control and completely arrest the hemorrhage were 28 and 55 seconds, respectively. The mechanisms of hemostasis appeared to be thermally induced coagulation necrosis of splenic tissue and occlusion of blood vessels by a mechanically induced homogenized splenic tissue. CONCLUSION HIFU may provide a useful method of hemostasis for actively bleeding spleen. Because of its ability to induce hemostasis at adjustable depth, HIFU may prove to be a useful cauterization method both in the operating room and for patients who are managed nonoperatively.