Patrick A. Coughlin

Detection of Atherosclerotic Inflammation by 68Ga-DOTATATE PET Compared to [18F]FDG PET Imaging

Background Inflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([18F]FDG PET), [18F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover. Objectives This study tested the efficacy of gallium-68-labeled DOTATATE (68Ga-DOTATATE), a somatostatin receptor subtype-2 (SST2)-binding PET tracer, for imaging atherosclerotic inflammation. Methods We confirmed 68Ga-DOTATATE binding in macrophages and excised carotid plaques. 68Ga-DOTATATE PET imaging was compared to [18F]FDG PET imaging in 42 patients with atherosclerosis. Results Target SSTR2 gene expression occurred exclusively in “proinflammatory” M1 macrophages, specific 68Ga-DOTATATE ligand binding to SST2 receptors occurred in CD68-positive macrophage-rich carotid plaque regions, and carotid SSTR2 mRNA was highly correlated with in vivo 68Ga-DOTATATE PET signals (r = 0.89; 95% confidence interval [CI]: 0.28 to 0.99; p = 0.02). 68Ga-DOTATATE mean of maximum tissue-to-blood ratios (mTBRmax) correctly identified culprit versus nonculprit arteries in patients with acute coronary syndrome (median difference: 0.69; interquartile range [IQR]: 0.22 to 1.15; p = 0.008) and transient ischemic attack/stroke (median difference: 0.13; IQR: 0.07 to 0.32; p = 0.003). 68Ga-DOTATATE mTBRmax predicted high-risk coronary computed tomography features (receiver operating characteristics area under the curve [ROC AUC]: 0.86; 95% CI: 0.80 to 0.92; p < 0.0001), and correlated with Framingham risk score (r = 0.53; 95% CI: 0.32 to 0.69; p <0.0001) and [18F]FDG uptake (r = 0.73; 95% CI: 0.64 to 0.81; p < 0.0001). [18F]FDG mTBRmax differentiated culprit from nonculprit carotid lesions (median difference: 0.12; IQR: 0.0 to 0.23; p = 0.008) and high-risk from lower-risk coronary arteries (ROC AUC: 0.76; 95% CI: 0.62 to 0.91; p = 0.002); however, myocardial [18F]FDG spillover rendered coronary [18F]FDG scans uninterpretable in 27 patients (64%). Coronary 68Ga-DOTATATE PET scans were readable in all patients. Conclusions We validated 68Ga-DOTATATE PET as a novel marker of atherosclerotic inflammation and confirmed that 68Ga-DOTATATE offers superior coronary imaging, excellent macrophage specificity, and better power to discriminate high-risk versus low-risk coronary lesions than [18F]FDG. (Vascular Inflammation Imaging Using Somatostatin Receptor Positron Emission Tomography [VISION]; NCT02021188)

Effect of frailty on short‐ and mid‐term outcomes in vascular surgical patients

Frailty is a multidimensional vulnerability resulting from age‐associated decline. The impact of frailty on outcomes was assessed in a cohort of vascular surgical patients.

Incidence and Outcomes of Severe Renal Impairment Following Ruptured Abdominal Aortic Aneurysm Repair.

INTRODUCTION Acute kidney injury (AKI) following ruptured abdominal aortic aneurysm (rAAA) repair is common and multifactorial. A standard definition of AKI after endovascular repair (EVAR), the Aneurysm Renal Injury Score (ARISe), has been proposed to facilitate standardised reporting and thus improve understanding of this issue. METHODS Data were collected retrospectively on AKI in a prospectively maintained database of all patients treated for rAAA in a single tertiary referral centre since the availability of routine out of hours emergency EVAR. The ARISe score was used to describe the degree of AKI and factors which correlated with poor renal outcomes were assessed. RESULTS Two-hundred and five patients were treated between January 2006 and April 2014. Of these, 125 were treated with open repair (OSR) and 80 were treated with EVAR. Severe AKI (defined as ARISe score ≥3) occurred in 36% of patients. After correction for confounders, patients treated with OSR were significantly more likely to develop severe AKI (43% vs. 26%, p = .02). There was no significant difference in preoperative serum creatinine between groups, but increased preoperative serum creatinine was strongly associated with severe AKI postoperatively (p < .001). Age, sex, endograft type, and preoperative CT scanning were not associated with differences in renal outcomes. Clamp position above renal arteries was predictive of severe AKI in patients treated with OSR (p < .01). Patients suffering severe AKI had significantly higher mortality at 30 days and 12 months (28% vs. 5% and 44% vs. 13%, p < .001 for both comparisons). CONCLUSION Severe AKI is common following successful repair of rAAA. In this large case series of high-risk patients, OSR was associated with significantly higher rates of severe AKI compared with EVAR, despite the increased dose of contrast involved in EVAR and the older age of these patients. In turn, severe AKI was associated with higher mortality rates.

Meta-analysis of contemporary short- and long-term mortality rates in patients diagnosed with critical leg ischaemia

Critical leg ischaemia (CLI) has been associated with high mortality rates. There is a lack of contemporary data on both short‐ and long‐term mortality rates in patients diagnosed with CLI.

Meta-analysis of prospective trials determining the short- and mid-term effect of elective open and endovascular repair of abdominal aortic aneurysms on quality of life.

Repair of an abdominal aortic aneurysm (AAA) is undertaken to prevent rupture. Intervention is by either open repair (OR) or a more minimally invasive endovascular repair (EVAR). Quality‐of‐life (QoL) analysis is an important health outcome and a number of single studies have assessed QoL following OR and EVAR. This was a meta‐analysis of published studies to assess the effect of an intervention on QoL in patients with an AAA.

Randomized clinical trial of co-amoxiclav versus no antibiotic prophylaxis in varicose vein surgery†

Wound infection rates of up to 16 per cent are reported following varicose vein surgery and the value of antibiotic prophylaxis in clean surgery remains unclear.

Statins: the holy grail of Abdominal Aortic Aneurysm (AAA) growth attenuation? A systematic review of the literature.

BACKGROUND In the era of Abdominal Aortic Aneurysm (AAA) screening, pharmacotherapies to attenuate AAA growth are sought. HMG Co-A reductase inhibitors (statins) have pleiotropic actions independent of their lipid lowering effects and have been suggested as potential treatment for small AAAs. We systematically review the clinical evidence for this effect. METHODS Medline, EMBASE and the Cochrane Central Register of Controlled Trials (1950-2011) were searched for studies reporting data on the role of statin therapy on AAA growth rate. No language restrictions were placed on the search. References of retrieved articles and pertinent journals were hand searched. Included studies were reviewed by 2 independent observers. The search retrieved 164 papers, 100 were irrelevant based on their title, 47 were reviews and 1 was a letter. 8 studies were excluded based on review of their abstract leaving 8 for inclusion in the study. RESULTS Eight observational clinical studies with a total of 4,466 patients were reviewed. Four studies demonstrated reduced AAA expansion in statin users while 4 studies failed to demonstrate this effect. The method of determining AAA growth rates varied significantly between the studies and the ability of many studies to control for misclassification bias was poor. CONCLUSIONS The claim that statins attenuate AAA growth remains questionable. Further prospective studies with stringent identification and verification of statin usage and a standardised method of estimating AAA growth rates are required. Statin type and dose also merit consideration.

Premorbid function, comorbidity, and frailty predict outcomes after ruptured abdominal aortic aneurysm repair.

OBJECTIVE Strategies to improve outcomes for patients with ruptured abdominal aortic aneurysm (rAAA) are becoming more evident. The aging population, however, continues to make the decision to intervene often difficult, especially given that traditional risk models do not reflect issues of aging and frailty. This study aimed to integrate measures of function alongside comorbidity- and frailty-specific factors to determine outcome. METHODS Patients treated for a rAAA between January 2006 and April 2014 were assessed. Demographics, mortality, and requirement for care after discharge as well as a variety of measures of function (physical, social, and psychological) and comorbidity were recorded. The primary outcome was 1-year mortality. Outcome models were generated using multivariate logistic regression and were compared with models of vascular frailty and AAA-related outcome. RESULTS Of 184 patients treated, 108 (59%) underwent an open surgical repair. The overall 30-day and 1-year mortality were 21.5% and 31.4%, respectively, with an overall median hospital length of stay of 13 days (interquartile range, 6-27 days). An optimal logistic regression model for 12-month mortality used Katz score, Charlson score, number of admission medicines, visual impairment, hearing impairment, hemoglobin level, and statin use as predictors, achieving an area under the receiver operating characteristic curve of 0.84. CONCLUSIONS This novel rAAA model incorporating function and comorbidity offers good predictive power for mortality. It is quick to calculate and may ultimately become helpful for both counseling and selection of patients and comparative audit at a time when outcome in patients with rAAA increasingly comes under the spotlight.

The effect of a 3-month supervised exercise programme on gait parameters of patients with peripheral arterial disease and intermittent claudication.

BACKGROUND The management of peripheral arterial disease with intermittent claudication includes angioplasty, pharmaceutical therapy, risk factor modification and exercise therapy. Supervised exercise programmes are used sporadically but may improve the distance that an individual with claudication can walk. The purpose of this study was to evaluate the effectiveness of a 3-month supervised exercise programme on improving gait parameters in patients with intermittent claudication. METHODS 12 participants were recruited (mean (SD) - age: 67.3 (6.8) years, height: 1.67 (0.09) m, mass: 79.4 (14.0) kg, ankle brachial pressure index: 0.73 (0.17)) from the local vascular unit and enrolled in a supervised exercise programme. Kinematic and kinetic data were collected at the following time points: pain-free walking, initial claudication pain, absolute claudication pain and after a patient-defined rest period. Data were collected before and after the 3-month supervised exercise programme. FINDINGS No significant differences were found in any of the gait parameters post-intervention including pain-free walking speed (P=0.274), peak hip extension (P=0.125), peak ankle plantarflexion (P=0.254), or first vertical ground reaction force peak (P=0.654). No significant gait differences were found across different levels of pain pre- or post-intervention. INTERPRETATION The lack of improvement post-intervention observed suggests that the current exercise protocol was not tailored to elicit significant improvements in patients with intermittent claudication, specifically. The results indicate that exercise programmes may show improved results post-intervention if they are longer in duration and varied in intensity. Further research into more detailed muscle and biomechanical adaptations is needed to inform exercise programmes specific to this population.

Effect of supervised exercise on physical function and balance in patients with intermittent claudication

The aim of the study was to identify whether a standard supervised exercise programme (SEP) for patients with intermittent claudication improved specific measures of functional performance including balance.