Gregorio A. Sicard

Diagnosis of Perioperative Myocardial Infarction with Measurement of Cardiac Troponin I

BACKGROUND Perioperative myocardial infarction is the most common cause of morbidity and mortality in patients who have had noncardiac surgery, but its diagnosis can be difficult. The present study was designed to determine whether the measurement of serum levels of cardiac troponin I, a highly sensitive and specific marker for cardiac injury, would help establish the diagnosis of myocardial infarction. METHODS We obtained preoperative measurements of MB creatine kinase, total creatine kinase, and cardiac troponin I, in addition to base-line electrocardiograms and two-dimensional echocardiograms, in 96 patients undergoing vascular surgery and 12 undergoing spinal surgery. Blood samples were obtained every 6 hours for at least the first 36 hours after surgery, and electrocardiograms were obtained daily; a second echocardiogram was obtained approximately three days after surgery. The appearance of a new abnormality in segmental-wall motion on the postoperative echocardiogram (that is, an abnormality that had not been seen on the preoperative echocardiogram) was considered to be indicative of perioperative infarction. RESULTS Eight patients who underwent vascular surgery had new abnormalities in segmental-wall motion and received a diagnosis of perioperative infarction. All eight had elevations of cardiac troponin I, and six had elevations of MB creatine kinase. Of the 100 patients without perioperative infarction detected by echocardiography, 19 had elevations of MB creatine kinase, and 1 had a slight elevation of cardiac troponin I. CONCLUSIONS The measurement of cardiac troponin I is a sensitive and specific method for the diagnosis of perioperative myocardial infarction. It avoids the high incidence of false diagnoses associated with the use of MB creatine kinase as a diagnostic marker.

Novel MRI Contrast Agent for Molecular Imaging of Fibrin Implications for Detecting Vulnerable Plaques

Background—Molecular imaging of thrombus within fissures of vulnerable atherosclerotic plaques requires sensitive detection of a robust thrombus-specific contrast agent. In this study, we report the development and characterization of a novel ligand-targeted paramagnetic molecular imaging agent with high avidity for fibrin and the potential to sensitively detect active vulnerable plaques. Methods and Results—The nanoparticles were formulated with 2.5 to 50 mol% Gd-DTPA-BOA, which corresponds to >50 000 Gd3+ atoms/particle. Paramagnetic nanoparticles were characterized in vitro and evaluated in vivo. In contradistinction to traditional blood-pool agents, T1 relaxation rate as a function of paramagnetic nanoparticle number was increased monotonically with Gd-DTPA concentration from 0.18 mL · s−1 · pmol−1 (10% Gd-DTPA nanoparticles) to 0.54 mL · s−1 · pmol−1 for the 40 mol% Gd-DTPA formulations. Fibrin clots targeted in vitro with paramagnetic nanoparticles presented a highly detectable, homogeneous T1-weighted contrast enhancement that improved with increasing gadolinium level (0, 2.5, and 20 mol% Gd). Higher-resolution scans and scanning electron microscopy revealed that the nanoparticles were present as a thin layer over the clot surface. In vivo contrast enhancement under open-circulation conditions was assessed in dogs. The contrast-to-noise ratio between the targeted clot (20 mol% Gd-DTPA nanoparticles) and blood was ≈118±21, and that between the targeted clot and the control clot was 131±37. Conclusions—These results suggest that molecular imaging of fibrin-targeted paramagnetic nanoparticles can provide sensitive detection and localization of fibrin and may allow early, direct identification of vulnerable plaques, leading to early therapeutic decisions.

The care of patients with an abdominal aortic aneurysm: The Society for Vascular Surgery practice guidelines

The Clinical Practice Council of the Society for Vascular Surgery charged a writing committee with the task of updating practice guidelines, initally published in 2003, for surgeons and physicians who are involved in the preoperative, operative, and postoperative care of patients with abdominal aortic aneurysms (AAA). This document provides recommendations for evaluating the patient, including risk of aneurysm rupture and associated medical co-morbidities, guidelines for selecting surgical or endovascular intervention, intraoperative strategies, perioperative care, long-term follow-up, and treatment of late complications. Decision making related to the care of patients with AAA is complex. Aneurysms present with varying risks of

Distal Aortic Perfusion and Cerebrospinal Fluid Drainage for Thoracoabdominal and Descending Thoracic Aortic Repair: Ten Years of Organ Protection

Objective To report the long-term results of our experience using cerebrospinal fluid drainage and distal aortic perfusion in descending thoracic and thoracoabdominal aortic repair. Summary Background Data Repair of thoracoabdominal and thoracic aortic aneurysm by the traditional clamp-and-go technique results in a massive ischemic insult to several major organ systems. Ten years ago, we began to use distal aortic perfusion and cerebrospinal fluid drainage (adjunct) to reduce end-organ ischemia. Methods Between January 1991 and February 2003, we performed 1004 thoracoabdominal or descending thoracic repairs. Adjunct was used in 741 (74%) of 1004. Multivariable data were analyzed by Cox regression. Number needed to treat was calculated as the reciprocal of the risk difference. Results Immediate neurologic deficit was 18 (2.4%) of 741 with adjunct and 18 (6.8%) of 263 without (P < 0.0009). In high-risk extent II aneurysms, the numbers were 11 (6.6%) of 167 with adjunct, and 11 (29%) of 38 without. Long-term survival was improved with adjunct (P < 0.002). The long-term survival results persisted after adjustment for age, extent II aneurysm, and preoperative renal function. Conclusion Use of adjunct over a long period of time has produced favorable results; approximately 1 neurologic deficit saved for every 20 uses of adjunct overall. In extent II aneurysms, where the effect is greatest, this increases to 1 saved per 5 uses. Adjunct is also associated with long-term survival, which is consistent with mitigation of ischemic end-organ injury. These long-term results indicate that cerebrospinal fluid drainage and distal aortic perfusion are safe and effective adjunct for reducing morbidity and mortality following thoracic and thoracoabdominal aortic repair.

Dobutamine stress echocardiography predicts surgical outcome in patients with an aortic aneurysm and peripheral vascular disease.

OBJECTIVES This study was conducted to assess the utility of dobutamine stress echocardiography for determining the presence of significant coronary artery disease and for predicting surgical outcome and long-term prognosis in patients scheduled to undergo peripheral vascular or aortic aneurysm surgery. BACKGROUND Assessment of coronary artery disease in patients scheduled to undergo peripheral vascular surgery can avoid perioperative complications. METHODS Dobutamine stress echocardiography was performed in 98 consecutive patients scheduled to undergo aortic or peripheral vascular surgery. Intravenous dobutamine was infused in a graded fashion, with two-dimensional digital echocardiographic monitoring of ventricular function and segmental wall motion. Group 1 (n = 70) consisted of patients who exhibited a normal response to dobutamine infusion (negative dobutamine study); group 2 (n = 23) comprised those patients with an abnormal response to dobutamine, characterized by the development of new or worsening wall motion abnormalities at rest, indicating the presence of myocardial ischemia (positive dobutamine study). Five patients with an inconclusive dobutamine study (because of inadequate heart rate) were excluded from analysis. RESULTS No major adverse effects occurred with testing in any patient. Sixty-eight of 70 patients with a negative study had peripheral vascular or aortic surgery performed without perioperative cardiac events (2 patients refused surgery). Nineteen of 23 patients with a positive study underwent coronary angiography and all had > 50% lumen narrowing in one or more major coronary artery distributions; 13 underwent coronary artery bypass grafting or angioplasty before peripheral vascular or aortic surgery and all had an uneventful perioperative period. Four of the 10 patients from group 2 who did not undergo coronary revascularization had a perioperative cardiac event (myocardial infarction in 2, an ischemic episode requiring urgent coronary bypass grafting in 1 and congestive heart failure in 1). CONCLUSIONS Positive and negative dobutamine study results are significant predictors of the presence or absence of perioperative events (20% vs. 0%, p = 0.003). A positive test warrants coronary angiography and further medical or surgical intervention, or both, but a negative test indicates a low likelihood of perioperative cardiac complications of aortic or peripheral vascular surgery. During the long-term follow-up period in this study (group 1 mean, 24 months; group 2 mean, 15 months), two patients (3%) from group 1 and three (15%) from group 2 developed cardiac complications (p = 0.038). Thus, dobutamine stress echocardiography is safe and can predict surgical outcome in patients undergoing aortic aneurysm repair or surgery for occlusive disease of the peripheral arteries. In addition, a negative test result is a strong predictor of decreased perioperative and long-term cardiac morbidity and mortality.

Preoperative treatment with doxycycline reduces aortic wall expression and activation of matrix metalloproteinases in patients with abdominal aortic aneurysms

PURPOSE Matrix metalloproteinases (MMPs) are considered to play a central role in the pathogenesis of abdominal aortic aneurysms (AAAs). Doxycycline (Dox) has direct MMP-inhibiting properties in vitro, and it effectively suppresses the development of elastase-induced AAAs in rodents. The purpose of this study was to determine if treatment with Dox suppresses MMPs within human aneurysm tissue and to elucidate the molecular mechanisms underlying this effect. METHODS Aneurysm tissues were obtained from 15 patients with an AAA, eight of whom had been treated with Dox before surgery (100 mg orally twice a day for 7 days). Protein extracts were examined by means of gelatin zymography and immunoblot analysis, and RNA was examined by means of reverse transcription-polymerase chain reaction (RT-PCR). The effects of Dox on MMP production were further examined in human THP-1 mononuclear phagocytes in vitro. RESULTS No detectable difference was found between groups by using substrate zymography as a means of assessing total MMP activity, but Dox treatment was associated with a slight (24.4%) reduction in the activated fraction of 72-kDa gelatinase (MMP-2; P <.05). In contrast, a 2.5-fold reduction in the amount of extractable 92-kDa gelatinase (MMP-9) protein in Dox-treated patients was revealed by means of immunoblot analysis (P <.05). Also, a 5.5-fold (81.9%) reduction in MMP-9 messenger RNA (mRNA) in Dox-treated patients was demonstrated by means of quantitative competitive RT-PCR (mean +/- SE, mol MMP-9/mol beta-actin: 1.3 +/- 0.5 vs 7.2 +/- 3.1; P <.04). There was no significant difference between groups in the relative expression of MMP-2 protein or mRNA. In cultured THP-1 monocytes stimulated with phorbol ester, the expression of MMP-9 protein and mRNA were both decreased after exposure to relevant concentrations of Dox in vitro. CONCLUSION In addition to its recognized effects as a direct MMP antagonist, Dox may influence connective tissue degradation within human aneurysm tissue by reducing monocyte/macrophage expression of MMP-9 mRNA and by suppressing the post-translational processing (activation) of proMMP-2. Through this complementary combination of mechanisms, treatment with Dox may be a particularly effective strategy for achieving MMP inhibition in patients with an AAA.

3D MRI-Based Multicomponent FSI Models for Atherosclerotic Plaques

A three-dimensional (3D) MRI-based computational model with multicomponent plaque structure and fluid–structure interactions (FSI) is introduced to perform mechanical analysis for human atherosclerotic plaques and identify critical flow and stress/strain conditions which may be related to plaque rupture. Three-dimensional geometry of a human carotid plaque was reconstructed from 3D MR images and computational mesh was generated using Visualization Toolkit. Both the artery wall and the plaque components were assumed to be hyperelastic, isotropic, incompressible, and homogeneous. The flow was assumed to be laminar, Newtonian, viscous, and incompressible. The fully coupled fluid and structure models were solved by ADINA, a well-tested finite element package. Results from two-dimensional (2D) and 3D models, based on ex vivo MRI and histological images (HI), with different component sizes and plaque cap thickness, under different pressure and axial stretch conditions, were obtained and compared. Our results indicate that large lipid pools and thin plaque caps are associated with both extreme maximum (stretch) and minimum (compression when negative) stress/strain levels. Large cyclic stress/strain variations in the plaque under pulsating pressure were observed which may lead to artery fatigue and possible plaque rupture. Large-scale patient studies are needed to validate the computational findings for possible plaque vulnerability assessment and rupture predictions.

Transabdominal versus retroperitoneal incision for abdominal aortic surgery: Report of a prospective randomized trial ☆ ☆☆ ★

PURPOSE The purpose of this study was to perform a randomized, prospective trial that compares the transabdominal with the retroperitoneal approach to the aorta for routine infrarenal aortic reconstruction. METHODS From August 1990 through November 1993, patients undergoing surgery for abdominal aortic aneurysm (AAA) disease or aortoiliac occlusive disease (AIOD) were asked to participate in a randomized trial comparing the transabdominal incision (TAI) to the retroperitoneal incision (RPI) for aortic surgery. One hundred forty-five patients were randomized, with 75 (41 with AAA and 34 with AIOD) in the TAI group and 70 (40 with AAA and 30 with AIOD) in the RPI group. There were no significant differences between the groups in terms of age, sex, postoperative pain control (epidural vs patient-controlled analgesia), or comorbid conditions, except for a higher incidence of chronic obstructive pulmonary disease in the TAI group (21 vs 8 patients). RESULTS The incidence of intraoperative complications was similar for both groups. After surgery, the incidence of prolonged ileus (p = 0.013) and small bowel obstruction (p = 0.05) was higher in the TAI group. Overall, the RPI group had significantly fewer complications (p < 0.0001). The overall postoperative mortality rate (two deaths) was 1.4%, with both occurring in the TAI group (p = 0.507). The RPI group also had significantly shorter stays in the intensive care unit (p = 0.006), a trend toward shorter hospitalization (p = 0.10), lower total hospital charges (p = 0.019), and lower total hospital costs (p = 0.017). There was no difference in pulmonary complications (p = 0.71). In long-term follow-up (mean 23 months), the RPI group reported more incisional pain (p = 0.056), but no difference was found in incisional hernias or bulges (p = 0.297). CONCLUSIONS We conclude that the RPI approach for abdominal aortic surgery is associated with fewer postoperative complications, shorter stays in the hospital and intensive care unit, and lower cost. There is, however, an increase in long-term incisional pain. Current methods of postoperative pain control seem to decrease the incidence of pulmonary complications.

Spontaneous closure of selected iatrogenic pseudoaneurysms and arteriovenous fistulae

PURPOSE We report our approach to the management of postcatheterization femoral artery pseudoaneurysms and arteriovenous fistulae in an attempt to determine the frequency of spontaneous resolution of selected lesions. METHODS We studied 196 pseudoaneurysms, 81 arteriovenous fistulae, and 9 combined lesions that were identified by duplex scan. Indications for immediate surgical repair included pseudoaneurysm greater than 3 cm, enlarging hematoma, pain, groin infection, nerve compression, limb ischemia, concomitant surgical procedure, and patient refusal or inability to comply with follow-up. All other lesions were observed. RESULTS One hundred thirty-nine patients underwent prompt surgical repair, and 147 patients were initially managed without operation. There were no limb-threatening complications associated with nonoperative management in this subset of patients. Eighty-six percent of the lesions being observed resolved spontaneously within a mean of 23 days, whereas 14% required surgical closure for a variety of reasons (at a mean of 111 days after the initial diagnosis). There was no statistically significant difference in the rate of spontaneous pseudoaneurysm closure (89%) as opposed to fistulae (81%) (p < 0.17). By life-table analysis, 90% of selected pseudoaneurysms had resolved by 2 months. Patients selected for observation underwent an average of 2.6 duplex scans per patient versus 1.4 scans per patient for those treated with immediate surgery (p < 0.01). CONCLUSION The natural history of stable pseudoaneurysms and arteriovenous fistulae is benign and frequently results in spontaneous resolution, which allows properly selected patients to be managed without operation.

Comparison between the transabdominal and retroperitoneal approach for reconstruction of the infrarenal abdominal aorta

To evaluate the efficacy of the retroperitoneal approach (RP) when compared with the transperitoneal (TP) approach in elective aortoiliac reconstruction, 104 consecutive cases were reviewed. From June 1983 through December 1985, 50 patients underwent aortoiliac reconstruction (26 for aortoiliac occlusive disease [AIOD] and 20 for abdominal aortic aneurysm [AAA]) through the TP approach and 54 patients underwent operation (30 for AIOD and 24 for AAA) through the RP approach. Both groups had similar revascularization procedures, associated diseases, and preoperative cardiac and pulmonary function parameters. The TP approach was associated with a larger intraoperative blood loss (1950 +/- 196 ml) when compared with the RP approach (1296 +/- 109 ml) (p less than 0.001). The intraoperative crystalloid requirements were also significantly higher for the TP approach (5994 +/- 296 ml) when compared with the RP approach (4455 +/- 295 ml) (p less than 0.0005). Similarly, the intraoperative blood requirements were higher for the TP approach (1235 +/- 115 ml) than the RP approach (853 +/- 61 ml) (p less than 0.001). Both groups had similar operative times. Nasogastric intubation and initiation of oral feeding was significantly prolonged in the TP group when compared with the RP group (p less than 0.001). Postoperative hospitalization was also considerably prolonged in the TP group when compared with the RP group (p less than 0.02). This experience demonstrates that the RP approach is a preferable alternative to the TP route in elective aortoiliac reconstruction.