Maani Hakimi

Surgical Therapy of Extracranial Carotid Artery Aneurysms: Long-Term Results over a 24-Year Period

BACKGROUND To evaluate long-term results of surgical therapy of extracranial carotid artery aneurysms (ECCA) and to provide a morphologic classification for individual surgical reconstruction techniques. PATIENT AND METHODS This retrospective analysis includes 57 patients (43 male, mean age 61.9 years.) with 64 carotid reconstructions for ECCA between 1980 and 2004. In 29 (50.9%) of the patients there was found a cerebral ischemic event as an initial symptom (18 transient ischemic attacks, 11 strokes). In patients without cerebral events, the presenting symptom was pulsatile cervical mass in 19 and cranial nerve dysfunction in 3 cases. ECCA was morphologically stratified in Type I=isolated aneurysms of the internal carotid artery (n=25), Type II=aneurysms of the complete internal carotid artery with involvement of the bifurcation (n=8), Type III=aneurysms of the carotid bifurcation (n=20), Type IV=combined aneurysm of the internal and common carotid artery (n=5) and Type V=isolated aneurysm of the common carotid artery (n=6). RESULTS Perioperative stroke rate was 1.6%. 4 patients suffered from transient ischemic attacks (6.3%). Permanent and transient cranial nerve injury rate was 6.3% and 20.3% respectively. After 5, 10, 15 and 20 years the actuarial survival was 90%, 77%, 65% and 57%. The ipsilateral stroke-free time was 96%, 96%, 93% and 87%, respectively. CONCLUSIONS Surgical reconstruction of extracranial carotid aneurysms is a safe procedure with good long-term results. The risk of a permanent, perioperative cerebral neurological deficit is low, but there is a considerable risk of cranial nerve injury.

IL-17A Influences Essential Functions of the Monocyte/Macrophage Lineage and Is Involved in Advanced Murine and Human Atherosclerosis

Atherosclerosis is a chronic inflammatory disease. Lesion progression is primarily mediated by cells of the monocyte/macrophage lineage. IL-17A is a proinflammatory cytokine, which modulates immune cell trafficking and is involved inflammation in (auto)immune and infectious diseases. But the role of IL-17A still remains controversial. In the current study, we investigated effects of IL-17A on advanced murine and human atherosclerosis, the common disease phenotype in clinical care. The 26-wk-old apolipoprotein E–deficient mice were fed a standard chow diet and treated either with IL-17A mAb (n = 15) or irrelevant Ig (n = 10) for 16 wk. Furthermore, essential mechanisms of IL-17A in atherogenesis were studied in vitro. Inhibition of IL-17A markedly prevented atherosclerotic lesion progression (p = 0.001) by reducing inflammatory burden and cellular infiltration (p = 0.01) and improved lesion stability (p = 0.01). In vitro experiments showed that IL-17A plays a role in chemoattractance, monocyte adhesion, and sensitization of APCs toward pathogen-derived TLR4 ligands. Also, IL-17A induced a unique transcriptome pattern in monocyte-derived macrophages distinct from known macrophage types. Stimulation of human carotid plaque tissue ex vivo with IL-17A induced a proinflammatory milieu and upregulation of molecules expressed by the IL-17A–induced macrophage subtype. In this study, we show that functional blockade of IL-17A prevents atherosclerotic lesion progression and induces plaque stabilization in advanced lesions in apolipoprotein E–deficient mice. The underlying mechanisms involve reduced inflammation and distinct effects of IL-17A on monocyte/macrophage lineage. In addition, translational experiments underline the relevance for the human system.

The effect of eversion and conventional-patch technique in carotid surgery on postoperative hypertension

OBJECTIVE Postcarotid endarterectomy hypertension (HTN) is associated with neurological and cardiac complications. The purpose of this study was to assess the influence of eversion carotid endarterectomy (E-CEA) and conventional carotid endarterectomy (C-CEA) on postoperative blood pressure in the first 4 days after surgery. METHODS Two hundred seventy-six consecutive CEAs that were performed between February 2008 and September 2009 were reviewed retrospectively with a computerized registry. After exclusion of patients with severe stroke (modified Rankin Scale of 3-5), prior contralateral and ipsilateral carotid surgery and more than 70% stenosis of the contralateral carotid artery, 201 cases remained (E-CEA group: n = 100 vs C-CEA group: n = 101) for analysis. Results in terms of systolic blood pressure, use of intravenous and oral vasodilators, alterations of the existing antihypertensive medications, and perioperative complications (neck hematoma, myocardial infarction, stroke, and death) were compared. RESULTS Groups were similar with regard to age, sex, and cardiovascular risk factors except for a higher incidence of nicotine use (59% vs 43%; P = .02) in the C-CEA group. Patients in the C-CEA group had a significantly higher percentage of symptomatic carotid artery stenosis (54% vs 23%, respectively; P < .0001). Despite a lower preoperative (baseline) mean systolic blood pressure (130 mm Hg vs 135 mm Hg; P = .02) patients in the E-CEA group had a significantly higher mean systolic blood pressure in the postoperative course up to the day 4 after surgery (134 mm Hg vs 126 mm Hg; P < .0001) and required more frequent intravenous (28% vs 9.9%; P = .001) and oral vasodilators (54% vs 27.7%; P = .0002) compared to those in the C-CEA group. Two-thirds (14 of 21 = 66%) of patients in the E-CEA group with preoperative high blood pressure (systolic blood pressure ≥140 mm Hg and diastolic pressure ≥90 mm Hg) required vasodilators and only one-third (11 of 33 = 33%) in the C-CEA group (P = .03). Atropine use due to bradycardia was necessary after 8 cases (8%) in the C-CEA group and only after 1 case (1%) in the E-CEA group (P = .03). Furthermore, the dosage of existing antihypertensive medications was increased and/or additional medications were prescribed twofold more in the E-CEA group (33% vs 17%; P = .009). No statistically significant difference was noted in the perioperative complication rate. CONCLUSION It is concluded that E-CEA is associated with significantly higher postoperative blood pressure that persists for at least 4 days after surgery. Patients with inadequate preoperative high blood pressure control are particularly at risk after E-CEA.

Finite element analysis of abdominal aortic aneurysms: predicted rupture risk correlates with aortic wall histology in individual patients.

Purpose: To evaluate a finite element analysis (FEA) model as a predictive tool for abdominal aortic aneurysm (AAA) rupture risk assessment. Methods: FEA of asymptomatic infrarenal AAAs in 15 men (mean age 72 years) was performed preoperatively using semiautomatic finite element analysis software (A4clinics) to calculate peak wall stress (PWS) and regions of highest and lowest rupture risk index (RRI). The areas of high and low RRI identified on the preoperative FEA were sampled during open surgery; aortic wall specimens were prepared for histological analysis. A semiquantitative score compared the histological findings from high and low rupture risk samples. Results: Significant correlation was found between histological AAA wall integrity and RRI in individual patients. AAA wall regions with highest RRI showed advanced histological disintegrity compared to regions with lower RRI within the same AAA: mean smooth muscle cells: 0.43 vs. 1.21, respectively (p=0.031); elastic fibers: 0.57 vs. 1.29, respectively (p=0.008); cholesterol plaque: 2.60 vs. 2.20, respectively (p=0.034); and calcified plaque: 2.27 vs. 1.40, respectively (p=0.017). The amount of calcified plaque was significantly correlated with PWS (r=0.528, p=0.043) by univariate regression analysis. However, there was no correlation between PWS or RRI and the histological findings between patients. Conclusion: These preliminary results show that high rupture risk regions estimated by FEA contain increased histopathological degeneration compared to low rupture risk samples within the same AAA. Until now, the role of FEA in predicting individual AAA rupture risk has not been established as a validated diagnostic tool. However, these data provide promising results for FEA model verification.

Increased Expression and Activation of Absent in Melanoma 2 Inflammasome Components in Lymphocytic Infiltrates of Abdominal Aortic Aneurysms

Chronic vascular inflammation is a key hallmark in the pathogenesis of abdominal aortic aneurysm (AAA). Recent investigations have suggested that the inflammasome, a cytosolic multiprotein complex that recognizes pathogen-associated molecular patterns, plays a role in atherosclerosis. However, its role in AAA inflammation has not yet been investigated. This pilot study analyzed inflammasome activation and its intramural localization in 24 biopsy samples from 11 patients with asymptomatic AAA versus 12 aortic samples from apparently healthy controls. Using a histological inflammation scale, we identified grade 2/3 inflammatory changes with lymphoid aggregates/tertiary lymphoid organs in 21 out of 24 AAA samples, whereas only 7 of the 12 control samples exhibited local grade 1 inflammatory changes. Strong expression levels of “apoptosis-associated speck-like protein with a caspase recruitment domain” (ASC), caspase-1, caspase-5 and “absent in melanoma 2” (AIM2) were detected by immunohis-tochemistry in both sporadic infiltrating lymphoid cells and lymphoid aggregates located in the outer media and adventitia of AAA samples. In contrast, inflammasome-positive cells were restricted to cholesterol plaque-associated areas and to single infiltrating cells in control aortas. Analysis of gene expression using real-time polymerase chain reaction (PCR) revealed significantly increased median mRNA levels of the inflammasome core components PYCARD (ASC), CASP1 (Caspase-1) and IL1B (IL-1β) in AAA tissue compared with normal aorta. Moreover, significantly increased median amounts of AIM2 protein and mature caspase-5 (p20) were found in samples associated with high rupture risk compared with paired low rupture risk samples of the same AAA patient. We conclude from our data that AAA-associated lymphoid cells are capable of inflammasome signaling, suggesting that inflammasome activation is involved in the chronic inflammatory process driving AAA progression.

Inflammation-related induction of absent in melanoma 2 (AIM2) in vascular cells and atherosclerotic lesions suggests a role in vascular pathogenesis.

BACKGROUND Absent in melanoma (AIM2) was recently identified to act as a cytosolic DNA sensor in innate immunity. Considering the role of chronic inflammation in atherosclerosis, we hypothesized that AIM2 may act as a damage signal that is activated in response to cellular stress likewise in vascular cells of larger arteries. We thus addressed AIM2 expression in healthy arterial wall and in different vascular lesions. In addition, AIM2 expression was characterized in cultured human aortic endothelial cells (HAoECs), smooth muscle cells (HAoSMCs), and T/G-HA-vascular smooth muscle cells (VSMCs) in response to different stimuli. METHODS Carotid and aortic lesions from patients who underwent surgery and normal arterial specimens were analyzed by immunohistochemistry for AIM2 expression. Cultured HAoECs, HAoSMCs, and T/G-HA-VSMCs were stimulated in vitro with proinflammatory cytokines (tumor necrosis factor-α, interferon-γ) or poly(dA:dT) and analyzed for AIM2 transcript and protein expression. RESULTS AIM2 was detected in ECs of the intima and vasa vasorum of normal carotid artery and aorta. Moreover, AIM2 was moderately expressed in VSMCs of normal media and intima layers, as well as in VSMCs of atherosclerotic lesions. Increased AIM2 expression was detected around the necrotic core of atherosclerotic carotid lesions and in the vasa vasorum neovasculature of aortic aneurysms. Subsequent in vitro analysis identified an endogenous AIM2 expression in cultured HAoECs, HAoSMCs, and T/G-HA-VSMCs that was markedly increased upon treatment of the cells with tumor necrosis factor-α, interferon-γ, or cytosolic DNA. CONCLUSIONS ECs and VSMC are able to respond to inflammatory signals by upregulation of AIM2 expression, indicating a role of AIM2 in vascular pathogenesis.

Type B aortic dissections: treating the many to benefit the few?

Purpose: It is now more than a decade since aortic stent-grafts were introduced clinically to provide a less invasive and potentially less harmful therapeutic option to treat type B aortic dissections. However, recent publications on best medical treatment and quality of life in patients with chronic type B dissection support conservative treatment due to the low incidence of aneurysm formation, rupture, and disease-related complications. Against this backdrop, we analyzed our experiences and now discuss whether the availability of endografts allowed us to change indications toward a more aggressive endovascular approach to acute and non-complex type B dissections, seeking to determine which patients we should treat and which ones we should observe. Methods: Between 1997 and 2008 in our institution in Heidelberg, we treated 172 patients with acute and chronic type B dissections, most (n=118, 69%) conservatively. However, 54 patients (40 men; mean age 57 years, range 30–82) underwent endovascular repair; 43% (n=23) were emergency cases. Patients were followed periodically with computed tomographic angiography. Results: Correct stent-graft deployment was achieved in 50 (93%) patients; the left subclavian artery was intentionally covered in 30 (55%) cases. Two carotid-subclavian bypass grafts were performed at the time of the endovascular repair due to partial coverage of the left common carotid artery. The perioperative complication rate was 19% (n=10), but there were no neurological sequelae. The 30-day mortality rate was 11% (n=6). Over a mean 32.1±25 months, 4 other patients died (18.5% overall mortality rate); survival estimates by Kaplan-Meier analysis were 80.4% and 66.1% after 1 and 5 years, respectively. Complete false lumen thrombosis was observed in 32 (60%) and a persisting completely patent false lumen in 3. The aortic expansion rate was 31% (17/54) overall. No difference was found between acute and chronic dissections in terms of survival (p=0.247). Conclusion: Despite a minimally invasive approach, complication and mortality rates for endovascular therapy of type B aortic dissections are considerable. Endografting is limited to symptomatic patients and those with chronic large aneurysmal expansion. At this stage in stent-graft development, asymptomatic patients benefit more from conservative treatment.

Eversion Carotid Endarterectomy is Associated with Decreased Baroreceptor Sensitivity Compared to the Conventional Technique

OBJECTIVE Impairment of baroreceptor sensitivity (BRS) has been shown to be associated with blood pressure instability after carotid endarterectomy (CEA). The aim of this study was to determine whether there is a difference in postoperative BRS changes following eversion CEA (E-CEA) and conventional CEA (C-CEA). METHODS Sixty-four patients undergoing E-CEA (n = 37) and C-CEA (n = 27) were prospectively studied. Non-invasive measurements of mean arterial pressure (MAP), cardiac output (CO) and total peripheral resistance (TPR) were perioperatively obtained over three 10-min periods. Baroreflex gain was calculated as the sequential cross-correlation between heart rate and beat-to-beat systolic blood pressure. RESULTS Compared with changes observed after C-CEA, E-CEA was associated with an increase in systolic pressure (SP) (P = 0.01), diastolic pressure (DP) (P = 0.008), MAP (P = 0.002) and heart rate (HR) (P = 0.03) on postoperative day 1 (POD-1). BRS decreased after E-CEA from 6.33 to 4.71 ms mmHg(-1) on POD-1 (P = 0.001) and to 5.26 ms mmHg(-1) on POD-3 (P = 0.0004). By contrast, BRS increased after C-CEA from 4.59 to 6.13 ms mmHg(-1) on POD-1 (P = 0.002) and to 6.27 ms mmHg(-1) on POD-3 (P < 0.0001). CONCLUSION E-CEA and C-CEA have different effects on BRS. This is associated with an altered haemodynamic behaviour after E-CEA and C-CEA, respectively. These findings are likely the result of carotid sinus nerve interruption during E-CEA and preservation with C-CEA.

Follow-up outcomes of hybrid procedures for thoracoabdominal aortic pathologies with special focus on graft patency and late mortality

OBJECTIVE The purpose of this study was to analyze midterm results of bypass patency and overall and aortic-related mortality rates of hybrid aortic procedures for thoracoabdominal aortic pathologies. METHODS A retrospective study was performed considering prospectively collected data in two centers. From January 2001 to December 2012, 45 patients (33 men; mean age, 67.8 ± 7.6 years) received hybrid aortic procedures for thoracoabdominal aortic diseases (31 atherosclerotic aneurysms, 7 chronic expanding type B aortic dissections, 2 penetrating aortic ulcers, and 5 pseudoaneurysms), corresponding to 155 revascularized visceral abdominal arteries. Elective/emergency and staged/simultaneous approaches were 31 of 14 and 28 of 17, respectively. Patient demographics, clinical risk factors, and aortic morphological and procedural data were collected. End points were technical success, 30-day morbidity, reintervention and mortality, bypass graft patency, freedom from reintervention, and overall and aortic-related mortality during midterm follow-up. Mean follow-up was 2.2 ± 2.4 years. RESULTS Technical success was achieved in 86.6% (39/45) of patients. Thirty-day morbidity rate was 60% (paraplegia/paraparesis: 13.3%, stroke: 6.7%, renal failure: 31.3%, permanent dialysis: 4.4%). Thirty-day freedom from reintervention rates were 67.1% and 78.5%, respectively. Thirty-day occlusion of revascularized visceral vessels occurred in 11 (7.1%, 11/155) target arteries. In-hospital mortality rate was 24.4%. Primary graft patency after 1, 2, and 4 years was 89.7%, 85.3%, and 79%, respectively. Bypass thrombosis or stenosis developed in nine (6.8%, 9/132) vessels during follow-up. Of these, three patients required reintervention and one died. Freedom from reintervention rates after 1, 2, and 4 years were 45.6%, 45.6%, and 34.2%, respectively. Overall and aortic-related mortality rates after 1, 2, and 4 years were 32.6%, 41.4%, and 45.3% and 9.1%, 13.9%, and 13.9%, respectively. CONCLUSIONS A hybrid procedure for thoracoabdominal aortic pathologies in high-risk patient is feasible but carries a significant rate of early and midterm reintervention and death. Long-term surveillance of the visceral bypass is necessary because one-third of the patients will have bypass-related complications.

Changes in baroreceptor sensitivity after eversion carotid endarterectomy

OBJECTIVE Posteversion carotid endarterectomy hypertension has been suggested to be associated with impaired baroreceptor sensitivity (BRS), which has been identified as a factor of prognostic relevance in patients with cardiovascular disease. The aim of this prospective single-center nonrandomized study was to describe the changes of BRS in the early postoperative period after eversion carotid endarterectomy (E-CEA). METHODS Spontaneous BRS and hemodynamic parameters such as blood pressure (BP), heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR) were evaluated preoperatively as well as postoperatively after 1 and 3 days using a noninvasive sequential cross-correlation method. Additionally, any modification in vasoactive medication due to BP derangement in the postoperative period was noted. Due to non-normal distribution of BRS, HR, and TPR samples, all measured values were expressed as medians with interquartile range (IQR), and a nonparametric test (Friedman) was performed. After adjustment for multiple testing, differences were considered statistically significant when the two-tailed P value was less than .0036. RESULTS Thirty-five patients (mean age, 71 years) with symptomatic or asymptomatic internal carotid artery stenosis were included. The BRS significantly decreased to a lower level 24 hours after surgery (4.71 ms/mm Hg [3.02-6.1]) than preoperatively (5.95 ms/mm Hg [4.68-10.86]; P < .0001), resulting in a within-patient difference of -2.46 ms/mm Hg (95% confidence interval [CI], -8.38 - -1.52). This difference (95% CI, [- 1.58 (-8.24 - -0.80)]) persisted at the 72-hour measurements (5.63 ms/mm Hg [3.23-7.69]; P = .0005). The HR, reflecting the sympathetic activity, increased 24 hours after the operation (69 bpm [61.3-77.7]) compared with preoperative values (63 bpm [57.9-73.2]; P = .005) (within-patient difference [95% CI] 3.7 [1.5-8.5]), and this increase reached significance at 72 hours (69 bpm [65.4-77.5]; P = .001) (within-patient difference [95% CI] 5.5 [2.3-8.8]). Values of systolic pressure, diastolic pressure, mean arterial pressure, CO, and TPR were not significantly different between pre- and postoperative measurements. Overall, 23 (66%) patients developed significant postoperative hypertension requiring aggressive management with additional medications. CONCLUSIONS E-CEA might have a decreasing influence on BRS, leading to increased sympathetic activity. Investigations of the longer-term effects of impaired BRS are warranted. These findings should be interpreted with caution, noting the limitation of an absent control group.