Massimiliano M. Marrocco-Trischitta

Contrast-Enhanced Ultrasound Imaging of Intraplaque Neovascularization in Carotid Arteries: Correlation With Histology and Plaque Echogenicity

OBJECTIVES This study was designed to evaluate contrast-enhanced ultrasound imaging of carotid atherosclerosis as a clinical tool to study intraplaque neovascularization. BACKGROUND Plaque neovascularization is associated with plaque vulnerability and symptomatic disease; therefore, imaging of neovascularization in carotid atherosclerosis may represent a useful tool for clinical risk stratification and monitoring the efficacy of antiatherosclerotic therapies. METHODS Thirty-two patients with 52 carotid plaques were studied by standard and contrast-enhanced ultrasound imaging. In 17 of these patients who underwent endarterectomy, the surgical specimen was available for histological determination of microvessel density by CD31/CD34 double staining. Plaque echogenicity and degree of stenosis at standard ultrasound imaging were evaluated for each lesion. Contrast-agent enhancement within the plaque was categorized as absent/peripheral (grade 1) and extensive/internal (grade 2). RESULTS In the surgical subgroup, plaques with higher contrast-agent enhancement showed a greater neovascularization at histology (grade 2 vs. grade 1 contrast-agent enhancement: median vasa vasorum density: 3.24/mm(2) vs. 1.82/mm(2), respectively, p = 0.005). In the whole series of 52 lesions, echolucent plaques showed a higher degree of contrast-agent enhancement (p < 0.001). Stenosis degree was not associated with neovascularization at histology or with the grade of contrast-agent enhancement. CONCLUSIONS Carotid plaque contrast-agent enhancement with sonographic agents correlates with histological density of neovessels and is associated with plaque echolucency, a well-accepted marker of high risk lesions, but it is unrelated to the degree of stenosis. Contrast-enhanced carotid ultrasound imaging may provide valuable information for plaque risk stratification and for assessing the response to antiatherosclerotic therapies, beyond that provided by standard ultrasound imaging.

Adenovirus-Mediated VEGF121 Gene Transfer Stimulates Angiogenesis in Normoperfused Skeletal Muscle and Preserves Tissue Perfusion After Induction of Ischemia

BACKGROUND Administration of angiogenic factors stimulates neovascularization in ischemic tissues. However, there is no evidence that angiogenesis can be induced in normoperfused skeletal muscles. We tested the hypothesis that adenovirus-mediated intramuscular (IM) gene transfer of the 121-amino-acid form of vascular endothelial growth factor (AdCMV.VEGF(121)) could stimulate neovascularization in nonischemic skeletal muscle and consequently attenuate the hemodynamic deficit secondary to surgically induced ischemia. METHODS AND RESULTS Rabbits and rats received IM injections of AdCMV.VEGF(121), AdCMV.Null, or saline in the thigh, 4 weeks (rabbits) or 2 weeks (rats) before femoral artery removal in the injected limb. In unoperated rats, at the site of injection of AdCMV.VEGF(121), we found 96% and 29% increases in length density of arterioles and capillaries, respectively. Increased tissue perfusion (TP) to the ischemic limb in the AdCMV.VEGF(121) group was documented, as early as day 1 after surgery, by improved blood flow to the ischemic gastrocnemius muscle measured by radioactive microspheres (AdCMV.VEGF(121)=5.69+/-0.40, AdCMV.Null=2.97+/-0.50, and saline=2.78+/-0.43 mL x min(-1) x 100 g(-1), P<0.001), more angiographically recognizable collateral vessels (angioscore) (AdCMV. VEGF(121)=50.58+/-1.48, AdCMV.Null=29.08+/-4.22, saline=11.83+/-1.90, P<0.0001), and improvement of the bioenergetic reserve of the gastrocnemius muscle as assessed by (31)P NMR spectroscopy. Follow-up studies showed that superior TP to the ischemic limb in the AdCMV.VEGF(121) group persisted until it was equalized by spontaneous collateral vessel development in untreated animals. CONCLUSIONS IM administration of AdCMV.VEGF(121) stimulates angiogenesis in normoperfused skeletal muscles, and the newly formed vessels preserve TP after induction of ischemia.

Aorto-oesophageal and aortobronchial fistulae following thoracic endovascular aortic repair: a national survey.

OBJECTIVE We evaluated the incidence of aorto-oesophageal (AEF) and aortobronchial (ABF) fistulae after thoracic endovascular aortic repair (TEVAR), and investigated their clinical features, determinants, therapeutic options and results. METHODS We conducted a voluntary national survey among Italian universities and hospital centres with a thoracic endovascular programme. RESULTS Thirty-nine centres were contacted, and 17 participated. Of the patients who underwent TEVAR between 1998 and 2008, 19/1113 (1.7%) developed AEF/ABF. Among indications to TEVAR, aortic pseudo-aneurysm was associated with the development of late AEF/ABF (P = 0.009). Further, emergent and complicated procedures resulted in increased risk of AEF/ABF (P = 0.008 and P < 0.001, respectively). Eight patients were treated conservatively, all of whom died within 30 days. Eleven patients underwent AEF/ABF surgical treatment, with a perioperative mortality of 64% (7/11). At a mean follow-up of 17.7 +/- 12.5 months, overall survival was 16% (3/19). CONCLUSIONS The incidence of AEF and ABF following TEVAR is not negligible, and is comparable to that following open repair. This finding warrants an ad hoc long-term follow-up after TEVAR, particularly in patients submitted to emergent and complicated procedures. Both surgical and endovascular treatment of AEF/ABF are associated with high mortality. However, conservative treatment does not appear to be a viable option.

Contrast-enhanced ultrasound imaging of periadventitial vasa vasorum in human carotid arteries

AIMS Arterial vasa vasorum (VV) are known to be involved in the atherosclerotic process. The aim of the present study was to explore whether ultrasound imaging with contrast agent is able to visualize adventitial VV in human carotid atherosclerosis. METHODS AND RESULTS We studied with standard ultrasound 25 patients with carotid stenosis >50% (ATS group) and 15 patients without carotid artery plaques and an intima-media thickness (IMT) <1.0 mm (CTRL group). All patients underwent contrast ultrasound to evaluate periadventitial VV and B-flow imaging (BFI) modality was used to improve and measure periadventitial flow signal. On contrast-enhanced images, a fast microbubble flow and a homogeneous and linear periadventitial contrast signal using BFI were detectable in the adventitial area in all patients of both groups. Periadventitial signal thickness by BFI was higher in patients with atherosclerosis than in the control group (mean +/- SD: CTRL 0.80+/-0.06 mm; ATS 1.10+/-0.11 mm; P<0.001). Moreover, considering the whole study population, the adventitial signal thickness significantly correlated with IMT values (r=0.88, r(2)=0.77; P<0.0001). CONCLUSION Periadventitial contrast signal was detected in all patients and BFI thickness was higher in patient with carotid atherosclerosis and correlated with IMT.

Endovascular treatment of aortoesophageal and aortobronchial fistulae

BACKGROUND Even when promptly recognized and treated, aortoesophageal (AEF) and aortobronchial (ABF) fistulae are highly lethal conditions. Open surgical repair also carries a high risk of mortality and morbidity. Several alternative strategies have been recently reported in the literature including thoracic endovascular aortic repair (TEVAR). However, relatively little is known about results of TEVAR for AEF and ABF due to their rarity and the lack of large surveys. METHODS A voluntary national survey was conducted among Italian universities and hospital centers with an endovascular program. Questionnaires were distributed by e-mail to participating centers and aimed to evaluate the results of endovascular repair of established AEF or ABF. RESULTS Seventeen centers agreed to participate and provided data on their patients. Between 1998 and 2008, a total of 1138 patients were treated with TEVAR. In 25 patients (2.2%), the indication to treatment was an AEF and/or an ABF. In 10 of these cases (40%), an associated open surgical procedure was also performed. Thirty-day mortality rate of AEF/ABF endovascular repair was 28% (7 cases). No cases of paraplegia or stroke were observed. Mean follow-up was 22.6 months (range, 1-62). Actuarial survival at 2 years was 55%. Among the 18 initial survivors, five patients (28%) underwent reintervention due to late TEVAR failure. CONCLUSIONS Stent grafting for AEF and ABF represents a viable option in emergent and urgent settings. However, further esophageal or bronchial repair is necessary in most cases. Despite less invasive attempts, mortality associated with these conditions remains very high.

Evaluation of a new disease-specific endovascular device for type B aortic dissection

OBJECTIVE The study objective was to evaluate the feasibility, safety, and early technical and clinical success rate of a new endovascular device specifically designed for aortic dissection that has recently become available in Europe. METHODS From June of 2005 to the present, the Zenith Dissection Endovascular System (William Cook Europe, Bjaerverskov, Denmark) was used in 11 selected patients (all male, with a median age of 58 years [range, 45-76 years]) with type B chronic aortic dissection with a compression or collapse of the true lumen. All procedures were performed under general anesthesia with preoperative cerebrospinal fluid drainage in 4 patients. One-step open surgical supra-aortic vessels re-routing was performed in 6 patients to obtain an adequate proximal landing zone: Left carotid-subclavian artery bypass was performed in 5 patients, and right-to-left common carotid artery bypass and left subclavian to common carotid artery transposition was performed in 1 patient. Clinical follow-up visits and computed tomography scans were obtained at 1, 6, and 12 months, and yearly thereafter. RESULTS A secondary technical success was obtained in all patients (100%), and 30-day clinical success was achieved in 10 patients (91%). A type IA entry flow was observed in 1 patient. No mortality was recorded. Occlusion of visceral/renal arteries, retrograde dissections, and device-induced tears in the intimal lamellae were not observed. Periprocedural morbidity included temporary renal failure in 1 patient and postimplantation syndrome with fever and leukocytosis for 23 days in 1 patient. No cases of paraplegia were recorded. At a median follow-up of 12 months (range, 2-30 months), we observed a clinical success rate of 91%. No migration of the device was observed. No late occlusion of the visceral or renal arteries was recorded at follow-up. CONCLUSION The perioperative and short-term follow-up results showed that the Zenith Dissection Endovascular System for the treatment of aortic dissection can be safely used without affecting the patency of the branches covered by the bare stent. However, these results need to be validated in a larger group of patients with a mid-term follow-up.

The Impact of Aortic Clamping Site on Glomerular Filtration Rate after Juxtarenal Aneurysm Repair

BACKGROUND Open repair of juxtarenal abdominal aortic aneurysms (JAAAs), which necessitates clamping above one (interrenal clamping, interRC) or both renal arteries (suprarenal clamping, supraRC), is associated with an increased risk of perioperative renal derangements. We reviewed our experience to investigate the impact of aortic clamping site during JAAA repair on peri- and postoperative glomerular filtration rate (GFR). METHODS Between January 2001 and March 2006, 32 patients (28 male, four female; mean age 70.5+/-5.6 years) were submitted to elective open repair of JAAA. SupraRC was required in 12 patients and performed with cold renal perfusion (CRP) in five cases; interRC was required in 20 and performed with CRP in eight. GFRs were estimated through postoperative day 4 using the Cockcroft-Gault equation and compared to those of concurrent controls undergoing infrarenal AAA repair, matched 1:1 by gender, age, aneurysm size, preoperative GFR, and left renal vein management. GFR values were also evaluated and compared between groups at a mean follow-up of 29.0+/-23.7 months. Renal dysfunction was defined as a decrease of GFR >or=20%. Statistics were determined as appropriate for the variables of interest. RESULTS No perioperative mortality was recorded and no differences in major complication rates were observed between groups (p=0.16). Operative time was longer in JAAA patients (154+/-47 vs. 132+/-41 min, p=0.019). Mean renal ischemia time was 16.7+/-7.7 min. Postoperatively, GFR values up to day 4 were significantly worse in JAAA patients compared to controls (p=0.0007), with a fourfold risk of renal dysfunction at postoperative day 4 (34% vs. 9%, odds ratio [OR]=4.44, 95% confidence interval [CI] 1.1-18.1; p=0.029). At univariate analysis, supraRC was found to be the only factor associated with perioperative renal dysfunction (OR=11.3, 95% CI 2.0-63.1; p=0.003). At follow-up, two patients with supraRC died and another two required dialysis permanently. When compared to those with interRC or infrarenal clamping, patients with supraRC showed a persistent renal dysfunction at follow-up (p=0.005). CONCLUSION Elective JAAA repair with renal ischemia time <or=30 min is safe, but supraRC entails a significant perioperative and mid-term GFR reduction. In contrast, interRC provides results similar to those obtained after infrarenal AAA repair, allowing postoperative recovery of renal function to preoperative values.

Management of congenital venous malformations of the vulva

OBJECTIVE To discuss the differential diagnosis and the management of venous malformations of the vulva. METHODS Five symptomatic patients were treated. The degree of pain and discomfort was self‐assessed by using a horizontal visual analog scale before and after treatment. Preoperative evaluation included Doppler ultrasound scanning in all patients and magnetic resonance imaging (MRI) in one. All patients had direct‐injection venography and sclerotherapy during the same session. Ethanol was used in two cases and polidocanol in three. Patients were followed‐up by means of Doppler ultrasound scanning and office visits. RESULTS All patients experienced marked swelling after the injection, and one developed cutaneous necrosis that healed within 2 weeks. Transient hemoglobinuria was observed in two cases. No early or late major complications occurred. At a mean follow‐up of 23 months (range 5–43), all patients experienced complete relief from symptoms and currently have normal vulvar sensation. Four patients had complete ablation of the treated lesion. In one patient the procedure resulted in a significant, albeit incomplete, occlusion of the lesion, and no further treatment was deemed necessary. From a cosmetic standpoint, both patients and physicians considered the results successful. CONCLUSION Vulvar venous malformations should be distinguished from vulvar varicosities, hematomas, soft‐tissue neoplasms, and other vascular anomalies. Doppler ultrasound, MRI, and direct‐injection venography are the most accurate diagnostic modalities. Sclerotherapy can successfully treat this condition. The procedure should be monitored with an imaging modality, preferably direct‐injection venography with digital subtraction serial imaging.

Outcome in cirrhotic patients after elective surgical repair of infrarenal aortic aneurysm

OBJECTIVE Abdominal surgery in patients with advanced liver disease has been reported to be associated with high morbidity and mortality rates. However, the surgical risk of infrarenal abdominal aortic aneurysm (AAA) repair in cirrhotics remains ill-defined. We reviewed our experience to investigate the predictors of the outcome in cirrhotic patients after elective AAA open repair. METHODS Between January 2001 and March 2006, 1189 patients underwent elective open repair of infrarenal AAA and 24 (2%) had a biopsy-proven cirrhosis (23 male, 1 female; mean age, 68 ± 7 years). The latter were retrospectively stratified according to the Child-Turcotte-Pugh (CTP) score and the Model for End-Stage Liver Disease (MELD) score. Operative variables, perioperative complications, and survival were recorded and compared with those of 48 concurrent noncirrhotic controls matched (2:1) by gender, age, aneurysm size, preoperative glomerular filtration rate, and type of reconstruction. The effect of CTP and MELD scores on midterm survival was investigated in cirrhotics with the Kaplan-Meier log-rank method. RESULTS No intraoperative or 30-day deaths were recorded. No significant differences in terms of major perioperative complications were observed between cirrhotic patients and controls. Operative time and intraoperative blood transfusion requirement were significantly higher in cirrhotics (162 ± 49 vs 132 ± 39 minutes; P = .007 and 273 ± 364 vs 84 ± 183 mL; P = .040, respectively). Hospital length of stay was nearly doubled in cirrhotic patients (11.0 ± 2.8 vs 5.8 ± 1.5 days; P < .0001). Twenty-two cirrhotic patients were classified as CTP A and two as CTP B. Median MELD score was 8 (range, 6-14). CTP class B was associated with higher intraoperative blood transfusion requirement (941 ± 54 vs 213 ± 314 mL; P = .029). At a mean follow-up of 30.7 ± 22.1 months, five deaths were recorded in cirrhotics, and three in controls. Actuarial survival at 2 years was 77.4% in cirrhotics and 97.8% in controls (log-rank test, P = .026). Both CTP B patients died within 6 months. CTP class B and a MELD score ≥10 were associated with reduced midterm survival rates (log-rank test, P < .0001 and P = .021, respectively). CONCLUSIONS In our experience, elective AAA open repair in relatively compensated cirrhotics was safely performed with an acceptable increase of the magnitude of the operation. However, the reduced life expectancy of cirrhotics with a MELD score ≥10 suggests that such a procedure may not be warranted in this subgroup of patients.

Chronic kidney disease classification stratifies mortality risk after elective stent graft repair of the thoracic aorta

OBJECTIVE Risk factors for perioperative and late mortality after thoracic endovascular aortic repair (TEVAR) remain ill-defined. In this study, we examined the prognostic significance of chronic kidney disease (CKD), a well-known predictor of death after thoracic aorta open repair, employing a stratification based on CKD stages derived from glomerular filtration rate (GFR) values. METHODS A prospective database was evaluated for 179 consecutive patients electively submitted to TEVAR between 1999 and 2007. Preoperative GFR was estimated by using the Cockcroft-Gault equation. Patient groups were stratified into four quartiles by baseline serum creatinine (SC) and GFR values, with quartile I being the lowest, and quartile IV the highest, and into the five CKD stages in reverse order (I GFR >or= 90 ml/min/1.73 m(2); II 60-89; III 30-59; IV 15-29; V < 15). Prognostic significance of preoperative GFR values and CKD stages were investigated by means of univariate and multivariate analyses, and the Kaplan-Meier log-rank method. RESULTS A primary technical success was achieved in 166 of 179 patients (92.7%), and an initial clinical success in 158 (88.3%). Thirty-day mortality was 5% (nine cases). Paraplegia or paraparesis were observed in 11 (6.1%) patients, and completely resolved in six cases after cerebrospinal fluid drainage. Preoperative GFR quartiles and CKD stages were significant predictors of 30-day mortality (P = .004 and P < .0001 respectively), whereas SC quartiles did not affect the outcome (P = .12). In particular, GFR quartile I (<60 ml/min/1.73 m(2)) was associated with a ten-fold greater risk of perioperative death compared with the other three quartiles (Odds Ratio 11.4, 95% Confidence Interval 2.3-57.0, P = .003). Midterm survival was 88.8% (159 of 179) at a mean follow-up of 35.6 +/- 23.7 months. Actuarial survival at 60 months was 57.8%, 81.1%, 92.3%, and 100% for GFR quartiles I to IV respectively (P < .0001), and 0.0%, 66.7%, 59.2%, 88.6%, and 100% (P < .0001) for CKD stage V to I respectively. At univariate analyses, age (P = .019), preoperative SC quartiles (P = .001), GFR quartiles (P = .0002), and CKD stages (P < .0001) were all predictive of mid-term mortality. At multivariate Cox proportional hazards regression analysis, only CKD stages remained independently associated with the outcome (P = .008). CONCLUSIONS GFR is an accurate prognostic predictor in patients submitted to TEVAR. Also, perioperative and midterm mortality directly correlate with the severity of CKD stages, allowing a risk stratification model to be employed both for risk-adjusted preoperative evaluation, and to establish accurate matching criteria for comparative studies.