Editor's Choice - Calcification of Thoracic and Abdominal Aneurysms is Associated with Mortality and Morbidity.

INTRODUCTION: Cardiovascular events are common in people with aortic aneurysms. Arterial calcification is a recognised predictor of cardiovascular outcomes in coronary artery disease. Whether calcification within abdominal and thoracic aneurysm walls is correlated with poor cardiovascular outcomes is not known. PATIENTS AND METHODS: Calcium scores were derived from computed tomography (CT) scans of consecutive patients with either infrarenal (AAA) or descending thoracic aneurysms (TAA) using the modified Agatston score. The primary outcome was subsequent all cause mortality during follow-up. Secondary outcomes were cardiovascular mortality and morbidity. RESULTS: A total of 319 patients (123 TAA and 196 AAA; median age 77 [71-84] years, 72% male) were included with a median follow-up of 30 months. The primary outcome occurred in 120 (37.6%) patients. In the abdominal aortic aneurysm group, the calcium score was significantly related to both all cause mortality and cardiac mortality (odds ratios (OR) of 2.246 (95% CI 1.591-9.476; p < 0.001) and 1.321 (1.076-2.762; p = 0.003)) respectively. In the thoracic aneurysm group, calcium score was significantly related to all cause mortality (OR 6.444; 95% CI 2.574-6.137; p < 0.001), cardiac mortality (OR 3.456; 95% CI 1.765-4.654; p = 0.042) and cardiac morbidity (OR 2.128; 95% CI 1.973-4.342; p = 0.002). CONCLUSIONS: Aortic aneurysm calcification, in either the thoracic or the abdominal territory, is significantly associated with both higher overall and cardiovascular mortality. Calcium scoring, rapidly derived from routine CT scans, may help identify high risk patients for treatment to reduce risk.

Variability in Atherosclerotic Disease Progression within the Infrainguinal Arterial Circulation is Dependent on Both Patient and Anatomical Factors.

BACKGROUND: Studies suggest 25% of patients with symptomatic peripheral arterial disease develop symptom progression over time, yet there is minimal data related to actual atherosclerotic progression. METHODS: Patients who underwent consecutive duplex imaging of the lower limb arteries, at least 6 months apart with no intervening arterial intervention, were identified. Atherosclerotic burden was determined for both femoropopliteal (FP) and crural (CR) arterial segments utilizing the Bollinger score (BoS). Overall change in BoS over time was determined, and patients were divided into group 1: disease progression and group 2: no change/disease regression. Patient demographics, comorbidities, and long-term outcomes were collated. RESULTS: A total of 215 FP segments (155 men; median age 74 years) were assessed with 82 limbs showing atherosclerotic disease progression. FP atherosclerotic progression was associated with increased age, a diagnosis of ischemic heart disease and hypertension, and a lack of prescription of both an antiplatelet therapy and an angiotensin-converting enzyme inhibitor (all P < 0.05). FP atherosclerotic progression was also associated with an increased longer term mortality rate. A total of 272 CR arterial segments (190 men; median age 74 years) were assessed with 86 limbs showing atherosclerotic disease progression. CR atherosclerotic disease progression was associated with a diagnosis of diabetes mellitus at baseline (P = 0.019). CONCLUSIONS: A number of variable factors predict atherosclerotic progression. Differences exist between factors and the arterial segments affected (FP/CR). This suggests that underlying atherosclerotic processes may vary depending on arterial segment, warranting further investigation.

Frailty predicts poor longer-term outcomes in patients following lower limb open surgical revascularization.

BACKGROUND: Frailty in vascular surgery patients is increasingly recognized as a marker of poor outcome. This provides particular challenges for patients with lower limb peripheral arterial disease who require surgical revascularization. This study aimed to assess the impact of frailty on short- and long-term outcome in this specific patient group using a specialty specific frailty score. METHODS: Patients undergoing open surgical revascularization for chronic limb ischemia (January 2015-December 2016) were assessed. Demographics, mode of admission, diagnosis, and site of surgery were recorded alongside a variety of frailty-specific characteristics. We calculated the previously validated Addenbrookes Vascular Frailty Score (AVFS) and Long AVFS (LAVFS). Primary outcome was 3-year mortality. RESULTS: Two hundred and sixty-one patients (75% men, median age 69 years) were studied. The median length of stay was 6 days with a 3-year mortality of 23%. The predictive power of vascular frailty scores showed that for 3-year mortality, area under the receiver operator curve values (AUROC) were specific for both the AVFS score (AUROC: 0.724, 95% CI: 0.654-0.794) and LAVFS Score (AUROC: 0.741, 95%CI: 0.670-0.813). Furthermore, the cumulative AVFS and LAVFS scores both predicted mortality over the follow-up period (P=0.0001) with increased mortality among patients with higher scores. CONCLUSIONS: Incremental worsening of frailty, determined using a specialty specific frailty score, predicts mortality risk in patients undergoing lower limb surgical revascularization.

Metabolic flexibility of mitochondrial respiratory chain disorders predicted by computer modelling.

Mitochondrial respiratory chain dysfunction causes a variety of life-threatening diseases affecting about 1 in 4300 adults. These diseases are genetically heterogeneous, but have the same outcome; reduced activity of mitochondrial respiratory chain complexes causing decreased ATP production and potentially toxic accumulation of metabolites. Severity and tissue specificity of these effects varies between patients by unknown mechanisms and treatment options are limited. So far most research has focused on the complexes themselves, and the impact on overall cellular metabolism is largely unclear. To illustrate how computer modelling can be used to better understand the potential impact of these disorders and inspire new research directions and treatments, we simulated them using a computer model of human cardiomyocyte mitochondrial metabolism containing over 300 characterised reactions and transport steps with experimental parameters taken from the literature. Overall, simulations were consistent with patient symptoms, supporting their biological and medical significance. These simulations predicted: complex I deficiencies could be compensated using multiple pathways; complex II deficiencies had less metabolic flexibility due to impacting both the TCA cycle and the respiratory chain; and complex III and IV deficiencies caused greatest decreases in ATP production with metabolic consequences that parallel hypoxia. Our study demonstrates how results from computer models can be compared to a clinical phenotype and used as a tool for hypothesis generation for subsequent experimental testing. These simulations can enhance understanding of dysfunctional mitochondrial metabolism and suggest new avenues for research into treatment of mitochondrial disease and other areas of mitochondrial dysfunction.