Native Structural and Functional Proteoform Characterization of the Prolyl-Alanyl-Specific Endoprotease EndoPro from Aspergillus niger.

The prolyl-alanyl-specific endoprotease (EndoPro) is an industrial enzyme produced in Aspergillus niger. EndoPro is mainly used for food applications but also as a protease in proteomics. In-depth characterization of this enzyme is essential to understand its structural features and functionality. However, there is a lack of analytical methods capable of maintaining both the structural and functional integrity of separated proteoforms. In this study, we developed an anion exchange (AEX) method coupled to native mass spectrometry (MS) for profiling EndoPro proteoforms. Moreover, we investigated purified EndoPro proteoforms with complementary MS-based approaches, including released N-glycan and glycopeptide analysis, to obtain a comprehensive overview of the structural heterogeneity. We showed that EndoPro has at least three sequence variants and seven N-glycosylation sites occupied by high-mannose glycans that can be phosphorylated. Each glycosylation site showed high microheterogeneity with ∼20 glycans per site. The functional characterization of fractionated proteoforms revealed that EndoPro proteoforms remained active after AEX-separation and the specificity of these proteoforms did not depend on N-glycan phosphorylation. Nevertheless, our data confirmed a strong pH dependence of EndoPro cleavage activity. Altogether, our study demonstrates that AEX-MS is an excellent tool to characterize complex industrial enzymes under native conditions.

A Real-World Experience With the Supera Interwoven Nitinol Stent in Femoropopliteal Arteries: Midterm Patency Results and Failure Analysis.

PURPOSE: To evaluate the safety and midterm patency of the Supera interwoven nitinol stent in a real-world population and determine deployment and patient-related factors that may predispose to loss of patency. METHODS: A retrospective analysis was conducted of 111 consecutive limbs from 97 patients (mean age 75.3 years; 68 men) with severe atherosclerotic disease of the superficial femoral and popliteal arteries that were treated with Supera stents between June 2012 and October 2014. Half the patients had claudication (56%); the remainder had rest pain (19%) and tissue loss (26%). Forty-eight (43%) lesions were chronic total occlusions, and more than half were classified as TransAtlantic Inter-Society Consensus C (22%) or D (30%). RESULTS: All 146 Supera stents (1.32 stents per limb) were deployed successfully, extending over a mean length of 175.5±130.5 mm to treat lesions averaging 151.5±127.1 mm long. At 30 days, Kaplan-Meier estimated freedom from death, target lesion revascularization, and amputation was 97.3%. Primary patency and freedom from clinically driven target lesion revascularization rates were 87.1% and 95.0% at 6 months, respectively, and 78.9% and 87.6% at 12 months, respectively. Four distinct mechanisms for failure were identified in the 13 limbs in which patency was lost; stent intussusception (n=4), compromised inflow or outflow (n=2), gross oversizing (n=1), and neoplastic thrombophilia (n=1); the cause of 5 occlusions could not be identified. CONCLUSION: In this heterogeneous group that included long and complex atheromatous femoropopliteal lesions, the Supera stent achieved excellent clinical and patency results at 1 year. Further improvement may be achieved through careful patient selection and the avoidance of deployment pitfalls.

Initial experience with the absorb bioresorbable vascular scaffold below the knee: six-month clinical and imaging outcomes.

PURPOSE: To investigate a new bioresorbable vascular scaffold for the treatment of focal tibial and distal popliteal lesions. METHODS: Tibial and distal popliteal angioplasty was performed in 15 limbs of 14 patients (9 men; median age 82 years) with critical limb ischemia (CLI, n=7) or severe claudication. The 18 lesions (mean length 22.2±14.0 mm) were implanted with 22 everolimus-eluting bioresorbable scaffolds (Absorb). Clinical and ultrasound follow-up was performed at 1, 3, 6, and 12 months to detect restenosis and evaluate safety, midterm restenosis rate, and clinical improvement. RESULTS: Immediate technical success was 100%, although a single limb suffered 2 scaffold thromboses on the first day; it was salvaged with repeat endovascular intervention. All patients were available for surveillance examinations during a follow-up of 6.1±3.9 months; no patient died. Of the 15 limbs in the analysis, clinical improvement was present in 12 (4 of 7 CLI patients); there was no amputation, bypass surgery, or evidence of binary restenosis on follow-up sonographic examination. CONCLUSION: Midterm follow-up for this small pilot sample demonstrates acceptable safety and patency results, together with freedom from all major adverse limb events, using the Absorb bioresorbable vascular scaffold below the knee.

Non-coronary atherosclerosis.

During the last decades, the clinical and research interest in atherosclerosis has been mostly focused on coronary arteries. After the publications of the European Society Guidelines and AHA/ACC Guidelines on Peripheral artery diseases, and of the Registry REduction in Atherothrombosis for Continued Health Registry, there has been an increased interest in atherosclerosis of the lower extremity arteries and its presence in multifocal disease. However, awareness in the general population and the medical community of non-coronary artery diseases, and of its major prognostic implications remain relatively low. The aim of this general review stemming out of an ESC Working Group on Peripheral Circulation meeting in 2011 is to enhance awareness of this complex disease highlighting the importance of the involvement of atherosclerosis at different levels with respect to clinical presentation, diagnosis, and co-existence of the disease in the distinct arterial territories. We also emphasize the need of an interdisciplinary approach to face the broad and complex spectrum of multifocal disease, and try to propose a series of tentative recommendations and measures to be implemented in non-coronary atherosclerosis.

Evaluating the effect of glycation on lipase activity using boronate affinity chromatography and mass spectrometry.

Protein glycation may occur naturally when reducing sugars and proteins coexist, which is often the case for industrial enzymes. The impact of post-translational modifications on enzyme performance (e.g., stability or function) is often not predictable, highlighting the importance of having appropriate analytical methodologies to monitor the influence of glycation on performance. Here, a boronate affinity chromatography method was developed to enrich glycated species followed by mass spectrometry for structural characterization and activity assays for functional assessment. This approach was applied to a (temperature-stressed) lipase used for food applications revealing that storage at -20 °C and 4 °C resulted in minor glycation (below 9%), whereas storage at 25 °C led to a higher glycation level with up to four sugars per lipase molecule. Remarkably, activity measurements revealed that glycation did not reduce lipase activity or stability. Altogether, this novel strategy is a helpful extension to the current analytical toolbox supporting development of enzyme products.

The Dutch chronic lower limb-threatening ischemia registry (THRILLER): A study protocol for popliteal and infrapopliteal endovascular interventions.

INTRODUCTION: Chronic limb-threatening ischemia (CLTI) is the end stage of peripheral arterial disease (PAD) and is associated with high amputation rates, mortality and disease-related health care costs. In infrapopliteal arterial disease (IPAD), endovascular revascularization should be considered for the majority of anatomical and clinical subgroups of CLTI. However, a gap of high-quality evidence exists in this field. The aim of the Dutch Chronic Lower Limb-Threatening Ischemia Registry (THRILLER) is to collect real world data on popliteal and infrapopliteal endovascular interventions. METHODS: THRILLER is a clinician-driven, prospective, multicenter, observational registry including all consecutive patients that undergo a popliteal or infrapopliteal endovascular intervention in seven Dutch hospitals. We estimate that THRILLER will include 400-500 interventions annually. Standardized follow-up visits with wound monitoring, toe pressure measurement and duplex ultrasonography will be scheduled at 6-8 weeks and 12 months after the intervention. The independent primary endpoints are primary patency, limb salvage and amputation free survival. Patients must give informed consent before participation and will be included according to predefined reporting standards. A data log of patients who meet the inclusion criteria but are not included in the registry will be maintained. We intend to conduct the first interim analysis two years after the start of inclusion. The results will be published in a scientific journal. DISCUSSION: Despite innovations in medical therapy and revascularization techniques, patients with CLTI undergoing endovascular revascularization still have a moderate prognosis. Previous prospective cohort studies were hampered by small sample sizes or heterogeneous reporting. Randomized controlled trials (RCTs) have high costs, potential conflicts of interest and give a limited reflection of daily practice. THRILLER aims to provide the largest prospective well phenotyped up-to-date dataset on treatment outcomes in CLTI patients to answer multiple underexplored research questions regarding diagnostics, medication, patient selection, treatment strategies and post intervention follow-up.

Fluvastatin and perioperative events in patients undergoing vascular surgery.

BACKGROUND: Adverse cardiac events are common after vascular surgery. We hypothesized that perioperative statin therapy would improve postoperative outcomes. METHODS: In this double-blind, placebo-controlled trial, we randomly assigned patients who had not previously been treated with a statin to receive, in addition to a beta-blocker, either 80 mg of extended-release fluvastatin or placebo once daily before undergoing vascular surgery. Lipid, interleukin-6, and C-reactive protein levels were measured at the time of randomization and before surgery. The primary end point was the occurrence of myocardial ischemia, defined as transient electrocardiographic abnormalities, release of troponin T, or both, within 30 days after surgery. The secondary end point was the composite of death from cardiovascular causes and myocardial infarction. RESULTS: A total of 250 patients were assigned to fluvastatin, and 247 to placebo, a median of 37 days before vascular surgery. Levels of total cholesterol, low-density lipoprotein cholesterol, interleukin-6, and C-reactive protein were significantly decreased in the fluvastatin group but were unchanged in the placebo group. Postoperative myocardial ischemia occurred in 27 patients (10.8%) in the fluvastatin group and in 47 (19.0%) in the placebo group (hazard ratio, 0.55; 95% confidence interval [CI], 0.34 to 0.88; P=0.01). Death from cardiovascular causes or myocardial infarction occurred in 12 patients (4.8%) in the fluvastatin group and 25 patients (10.1%) in the placebo group (hazard ratio, 0.47; 95% CI, 0.24 to 0.94; P=0.03). Fluvastatin therapy was not associated with a significant increase in the rate of adverse events. CONCLUSIONS: In patients undergoing vascular surgery, perioperative fluvastatin therapy was associated with an improvement in postoperative cardiac outcome. (Current Controlled Trials number, ISRCTN83738615.)

Sudden death during follow-up after new-onset ventricular tachycardia in vascular surgery patients.

BACKGROUND: Vascular surgery patients are at increased risk for late sudden cardiac death. Identification of patients at risk during surgery offers the opportunity for focused therapy. METHODS: We monitored 483 vascular surgery patients who had no documented history of arrhythmias to identify perioperative new-onset ventricular tachyarrhythmia (VT) and myocardial ischemia using a continuous electrocardiographic (ECG) device for 72 hours. Cardiac risk factors, left ventricular ejection fraction (LVEF), medical therapy, inflammation status, and perioperative ischemia in relation to arrhythmia were noted in all patients. During follow-up, event-based outcomes analysis was used to describe survival. RESULTS: New-onset perioperative VT was detected in 33 patients (6.8%). A higher percentage of patients experiencing perioperative VT had reduced LVEF preoperatively than those without VT (24% vs 12%; P = .04). Additionally, fewer patients experiencing VT were receiving statins than those without (70% vs 85%; P = .02). Patients experiencing VT had a higher incidence of myocardial ischemia (30% vs 18%; P = .10). Perioperative VT was preceded by ischemia in only 60% of the cases. The overall cohort survival was 83% at 24-month follow-up (interquartile range [IQR], 1.1-1.3). Sudden cardiac death free survival among patients experiencing VT was less than in those without (79% vs 92%; P = .02). After adjusting for gender, cardiac risk factors, and type of surgery, new-onset perioperative VT was associated with sudden cardiac death (hazard ratio [HR], 2.6; 95% confidence interval [CI], 1.1-5.8). CONCLUSION: Perioperative VT is likely to be associated with late sudden cardiac death and decreased survival. Continuous perioperative ECG is an effective method to identify VT and may allow improved management of these patients.

Covered stent grafts for relining of chronically occluded femoro-popliteal bypasses in frail patients.

In four high-risk patients with chronically occluded femoro-popliteal bypass suffering from Rutherford 4-5 chronic limb threatening ischemia we performed, as an alternative for redo surgery, endovasculair relining with covered stent grafts. During follow-up (3, 8, 14 and 20 months) one patient had redo percutaneous intervention and eventually below-the-knee amputation.

The efficacy and safety of clopidogrel in vascular surgery patients with immediate postoperative asymptomatic troponin T release for the prevention of late cardiac events: Rationale and design of the Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echo-VII (DECREASE-VII) trial.

BACKGROUND: Major vascular surgery patients are at high risk for developing asymptomatic perioperative myocardial ischemia reflected by a postoperative troponin release without the presence of chest pain or electrocardiographic abnormalities. Long-term prognosis is severely compromised and characterized by an increased risk of long-term mortality and cardiovascular events. Current guidelines on perioperative care recommend single antiplatelet therapy with aspirin as prophylaxis for cardiovascular events. However, as perioperative surgical stress results in a prolonged hypercoagulable state, the postoperative addition of clopidogrel to aspirin within 7 days after perioperative asymptomatic cardiac ischemia could provide improved effective prevention for cardiovascular events. STUDY DESIGN: DECREASE-VII is a phase III, randomized, double-blind, placebo-controlled, multicenter clinical trial designed to evaluate the efficacy and safety of early postoperative dual antiplatelet therapy (aspirin and clopidogrel) for the prevention of cardiovascular events after major vascular surgery. Eligible patients undergoing a major vascular surgery (abdominal aorta or lower extremity vascular surgery) who developed perioperative asymptomatic troponin release are randomized 1:1 to clopidogrel or placebo (300-mg loading dose, followed by 75 mg daily) in addition to standard medical treatment with aspirin. The primary efficacy end point is the composite of cardiovascular death, stroke, or severe ischemia of the coronary or peripheral arterial circulation leading to an intervention. The evaluation of long-term safety includes bleeding defined by TIMI criteria. Recruitment began early 2010. The trial will continue until 750 patients are included and followed for at least 12 months. SUMMARY: DECREASE-VII is evaluating whether early postoperative dual antiplatelet therapy for patients developing asymptomatic cardiac ischemia after vascular surgery reduces cardiovascular events with a favorable safety profile.

Risk factors and outcome of new-onset cardiac arrhythmias in vascular surgery patients.

BACKGROUND: The pathophysiology of new-onset cardiac arrhythmias is complex and may bring about severe cardiovascular complications. The relevance of perioperative arrhythmias during vascular surgery has not been investigated. The aim of this study was to assess risk factors and prognosis of new-onset arrhythmias during vascular surgery. METHODS: A total of 513 vascular surgery patients, without a history of arrhythmias, were included. Cardiac risk factors, inflammatory status, and left ventricular function (LVF; N-terminal pro-B-type natriuretic peptide and echocardiography) were assessed. Continuous electrocardiography (ECG) recordings for 72 hours were used to identify ischemia and new-onset arrhythmias: atrial fibrillation, sustained ventricular tachycardia, supraventricular tachycardia, and ventricular fibrillation. Logistic regression analysis was applied to identify preoperative risk factors for arrhythmias. Cox regression analysis assessed the impact of arrhythmias on cardiovascular event-free survival during 1.7 years. RESULTS: New-onset arrhythmias occurred in 55 (11%) of 513 patients: atrial fibrillation, ventricular tachycardia, supraventricular tachycardia, and ventricular fibrillation occurred in 4%, 7%, 1%, and 0.2%, respectively. Continuous ECG showed myocardial ischemia and arrhythmias in 17 (3%) of 513 patients. Arrhythmia was preceded by ischemia in 10 of 55 cases. Increased age and reduced LVF were risk factors for the development of arrhythmias. Multivariate analysis showed that perioperative arrhythmias were associated with long-term cardiovascular events, irrespective of the presence of perioperative ischemia (hazard ratio 2.2, 95% CI 1.3-3.8, P = .004). CONCLUSION: New-onset perioperative arrhythmias are common after vascular surgery. The elderly and patients with reduced LVF show arrhythmias. Perioperative continuous ECG monitoring helps to identify this high-risk group at increased risk of cardiovascular events and death.

Postoperative mortality in The Netherlands: a population-based analysis of surgery-specific risk in adults.

BACKGROUND: Few data are available that systematically describe rates and trends of postoperative mortality for fairly large, unselected patient populations. METHODS: This population-based study uses a registry of 3.7 million surgical procedures in 102 hospitals in The Netherlands during 1991-2005. Patients older than 20 yr who underwent an elective, nonday case, open surgical procedure were enrolled. Patient data included main (discharge) diagnosis, secondary diagnoses, dates of admission and discharge, death during admission, operations, age, sex, and a limited number of comorbidities classified according to the International Classification of Diseases 9th revision Clinical Modification. The main outcome measure was postoperative all-cause mortality. Univariable and multivariable logistic regression analyses were applied to evaluate the relationship between type of surgery and the main outcome. RESULTS: Postoperative all-cause death was observed in 67,879 patients (1.85%). In a model based on a classification into 11 main surgical categories, breast surgery was associated with lowest mortality (adjusted incidence, 0.07%), and vascular surgery was associated with highest mortality (adjusted incidence, 5.97%). In a model based on 36 surgical subcategories, the adjusted mortality ranged from 0.07% for hernia nuclei pulposus surgery to 18.5% for liver transplant. The c-index of the 36-category model was 0.88, which was significantly (P < 0.001) higher than the c-index that was associated with the simple surgical classification (low vs. high risk) in the commonly used Revised Cardiac Risk Index (c-index, 0.83). CONCLUSIONS: This population-based study provided a detailed and contemporary overview of postoperative mortality for the entire surgical spectrum, which may act as reference standard for surgical outcome in Western populations.

Prognostic implications of asymptomatic left ventricular dysfunction in patients undergoing vascular surgery.

BACKGROUND: The prognostic value of heart failure symptoms on postoperative outcome is well acknowledged in perioperative guidelines. The prognostic value of asymptomatic left ventricular (LV) dysfunction remains unknown. This study evaluated the prognostic implications of asymptomatic LV dysfunction in vascular surgery patients assessed with routine echocardiography. METHODS: Echocardiography was performed preoperatively in 1,005 consecutive vascular surgery patients. Systolic LV dysfunction was defined as LV ejection fraction less than 50%. Ratio of mitral-peak velocity during early and late filling, pulmonary vein flow, and deceleration time was used to diagnose diastolic LV dysfunction. Troponin-T measurements and electrocardiograms were performed routinely perioperatively. Multivariate regression analyses evaluated the relation between LV function and the study endpoints, 30-day cardiovascular events, and long-term cardiovascular mortality. RESULTS: Left ventricular dysfunction was diagnosed in 506 (50%) patients of which 80% were asymptomatic. In open vascular surgery (n = 649), both asymptomatic systolic and isolated diastolic LV dysfunctions were associated with 30-day cardiovascular events (odds ratios 2.3, 95% confidence interval [CI] 1.4-3.6 and 1.8, 95% CI 1.1-2.9, respectively) and long-term cardiovascular mortality (hazard ratios 4.6, 95% CI 2.4-8.5 and 3.0, 95% CI 1.5-6.0, respectively). In endovascular surgery (n = 356), only symptomatic heart failure was associated with 30-day cardiovascular events (odds ratio 1.8, 95% CI 1.1-2.9) and long-term cardiovascular mortality (hazard ratio 10.3, 95% CI 5.4-19.3). CONCLUSIONS: This study demonstrated that asymptomatic LV dysfunction is predictive for 30-day and long-term cardiovascular outcome in open vascular surgery patients. These data suggest that preoperative risk stratification should include not only solely heart failure symptoms but also routine preoperative echocardiography to risk stratify open vascular surgery patients.

Bisoprolol and fluvastatin for the reduction of perioperative cardiac mortality and myocardial infarction in intermediate-risk patients undergoing noncardiovascular surgery: a randomized controlled trial (DECREASE-IV).

OBJECTIVE: This study evaluated the effectiveness and safety of beta-blockers and statins for the prevention of perioperative cardiovascular events in intermediate-risk patients undergoing noncardiovascular surgery. SUMMARY BACKGROUND DATA: Beta-blockers and statins reduce perioperative cardiac events in high-risk patients undergoing vascular surgery by restoring the myocardial oxygen supply/demand balance and/or stabilizing coronary plaques. However, their effects in intermediate-risk patients remained ill-defined. METHODS: In this randomized open-label 2 x 2 factorial design trial 1066 intermediate cardiac risk patients were assigned to bisoprolol, fluvastatin, combination treatment, or control therapy before surgery (median: 34 days). Intermediate risk was defined by an estimated risk of perioperative cardiac death and myocardial infarction (MI) of 1% to 6%, using clinical data and type of surgery. Starting dose of bisoprolol was 2.5 mg daily, titrated to a perioperative heart rate of 50 to 70 beats per minute. Fluvastatin was prescribed in a fixed dose of 80 mg. The primary end point was the composite of 30-day cardiac death and MI. This study is registered in the ISRCTN registry and has the ID number ISRCTN47637497. RESULTS: Patients randomized to bisoprolol (N = 533) had a lower incidence of perioperative cardiac death and nonfatal MI than those randomized to bisoprolol-control (2.1% vs. 6.0% events; hazard ratios: 0.34; 95% confidence intervals: 0.17-0.67; P = 0.002). Patients randomized to fluvastatin experienced a lower incidence of the end point than those randomized to fluvastatin-control therapy (3.2% vs. 4.9% events; hazard ratios: 0.65; 95% confidence intervals: 0.35-1.10), but statistical significance was not reached (P = 0.17). CONCLUSION: Bisoprolol was associated with a significant reduction of 30-day cardiac death and nonfatal MI, while fluvastatin showed a trend for improved outcome.

Intima media thickness of the common carotid artery in vascular surgery patients: a predictor of postoperative cardiovascular events.

BACKGROUND: Cardiovascular (CV) complications are the leading cause of morbidity and mortality in vascular surgery patients. The Revised Cardiac Risk (RCR) index, identifying cardiac risk factors, is commonly used for preoperative risk stratification. However, a more direct marker of the underlying atherosclerotic disease, such as the common carotid artery intimamedia thickness (CCA-IMT) may be of predictive value as well. The current study evaluated the prognostic value of the CCA-IMT for postoperative CV outcome. METHODS: In 508 vascular surgery patients, the CCA-IMT was measured using high-resolution B-mode ultrasonography. We recorded the RCR factors: ischemic heart disease, heart failure, cerebrovascular disease, diabetes mellitus, and renal dysfunction. Repeated Troponin T measurements and electrocardiograms were performed postoperatively. The study end point was the composite of 30-day CV events and long-term CV mortality. Multivariable regression analyses were used to assess the additional value of CCA-IMT for the prediction of cardiac events. RESULTS: In total, 30-day events and long-term cardiovascular mortality were noted in 122 (24%) and 81 (16%) patients, respectively. The optimal predictive value of CCA-IMT, using receiver-operating characteristic curve analysis, for the prediction of CV events was calculated to be 1.25 mm (sensitivity 70%, specificity 80%). An increased CCA-IMT was independently associated with 30-day CV events (OR 2.20, 95% CI 1.38-3.52) and long-term CV mortality (HR 6.88, 95% CI 4.11-11.50), respectively. CONCLUSIONS: This study shows that an increased CCA-IMT has prognostic value in vascular surgery patients to predict 30-day CV events and long-term CV mortality, incremental to the RCR index.

Plasma N-terminal pro-B-type natriuretic peptide as a predictor of perioperative and long-term outcome after vascular surgery.

OBJECTIVE: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is secreted by the heart in response to ventricular wall stress and has prognostic value in patients with heart failure, coronary artery disease, and heart valve abnormalities. Postoperative and long-term outcome is also related to these risk factors. This study assessed the additional prognostic value of NT-proBNP levels as a simple objective risk marker for postoperative cardiac events among vascular surgery patients. METHODS: A detailed cardiac history (angina, myocardial infarction, age >70 years, diabetes mellitus, renal failure, stroke, heart failure), resting echocardiography, and NT-proBNP levels were obtained in 400 vascular surgery patients. Postoperative troponin-T levels and an electrocardiogram were obtained on days 1, 3, 7, and 30, and whenever clinically indicated. Patients were monitored every 6 months at the outpatient clinic. Study end points were perioperative cardiac events (ie, composite of cardiac death, myocardial infarction, and troponin release) and long-term all-cause mortality. The additional value of NT-proBNP was assessed with multivariable regression analysis. The optimal cutoff value was assessed by receiver operating characteristic curve analysis. RESULTS: Postoperative troponin T release occurred in 79 patients (20%). Cardiac risk factors were used to classify patients as low (0 risk factors), intermediate (1 to 2), and high (>3) cardiac risk (event rate of 7%, 15%, and 37%, respectively). The median NT-proBNP level was 206 pg/mL (interquartile range, 80-548 pg/mL). The risk of postoperative cardiac events was augmented with increasing NT-proBNP, irrespective of underlying cardiac risk factors and type of vascular surgery. In addition to cardiac risk factors only (C index, 0.66) or cardiac risk factors and site and type of surgery (C index, 0.81), NT-proBNP was an excellent tool for further risk stratification (C index, 0.86), with an optimal cutoff value of 350 pg/mL. In multivariate analysis, NT-proBNP >350 pg/mL remained significantly associated with perioperative cardiac events (odds ratio [OR], 4.7; 95% confidence interval [CI], 2.1-10.5, P < .001). NT-proBNP >350 pg/mL was also associated with an independent 1.9-fold (95% CI 1.1-3.2) increased risk for long-term mortality during a median follow-up of 2.4 years. CONCLUSION: NT-proBNP is an independent prognostic marker for postoperative cardiac events and long-term mortality in patients undergoing different types of vascular surgery and might be used for preoperative cardiac risk stratification.

Perioperative asymptomatic cardiac damage after endovascular abdominal aneurysm repair is associated with poor long-term outcome.

BACKGROUND: Endovascular abdominal aortic aneurysm (AAA) repair (EVAR) is associated with a decreased incidence of perioperative cardiac complications compared with open repair. However, EVAR is not associated with long-term survival benefit. This study assessed the effect of perioperative asymptomatic cardiac damage after EVAR on long-term prognosis. METHODS: In 220 patients undergoing elective EVAR, routine sampling for levels of cardiac troponin T and electrocardiography (ECG) were performed on days 1, 3, and 7 during the patient's hospital stay. Elevated cardiac troponin T was defined as serum concentrations >or=0.01 ng/mL. Asymptomatic cardiac damage was defined as cardiac troponin T release without symptoms or ECG changes. The median follow-up was 2.9 years. Survival status was obtained by contacting the Office of Civil Registry. RESULTS: Release of cardiac troponin T (median, 0.08 ng/mL) occurred in 24 of 220 patients, of whom 20 (83%) were asymptomatic and without ECG changes. Patients with asymptomatic cardiac damage had a mortality rate of 49% [corrected] after 2.9 years vs 15% [corrected] for patients without perioperative cardiac damage (P < .001). Also after adjustment for clinical risk factors and medication use applying multivariate Cox regression analysis, asymptomatic cardiac damage was associated with a 2.3-fold increased risk for death (95% confidence interval, 1.1-5.1). Statin use was associated with a reduced long-term risk for death (hazard ratio, 0.5; 95% confidence interval, 0.3-0.9). CONCLUSION: Asymptomatic cardiac damage in patients undergoing EVAR is associated with poor long-term outcome. Routine perioperative cardiac screening after EVAR might be warranted.

The interrelationship between preoperative anemia and N-terminal pro-B-type natriuretic peptide: the effect on predicting postoperative cardiac outcome in vascular surgery patients.

INTRODUCTION: N-terminal pro-B-type natriuretic peptide (NT-proBNP) predicts adverse cardiac outcome in patients undergoing vascular surgery. However, several conditions might influence this prognostic value, including anemia. In this study, we evaluated whether anemia confounds the prognostic value of NT-proBNP for predicting cardiac events in patients undergoing vascular surgery. METHODS: A detailed cardiac history, resting echocardiography, and hemoglobin and NT-proBNP levels were obtained in 666 patients before vascular surgery. Anemia was defined as serum hemoglobin <13 g/dL for men and <12 g/dL for women. Troponin T measurements and 12-lead electrocardiograms were performed on postoperative days 1, 3, 7, and 30 and whenever clinically indicated. The primary end point of the study was the composite of 30-day postoperative cardiovascular death, nonfatal myocardial infarction, and troponin T release. Receiver operating characteristic curve analysis was used to assess the optimal cutoff value of NT-proBNP for the prediction of the composite end point. Multivariable regression analysis was used to assess the additional value of NT-proBNP for the prediction of postoperative cardiac events in nonanemic and anemic patients. RESULTS: Anemia was present in 206 patients (31%) before surgery. Hemoglobin level was inversely related with the NT-proBNP levels (beta coefficient = -2.242; P = 0.025). The optimal predictive cutoff value of NT-proBNP for predicting the composite cardiovascular outcome was 350 pg/mL. After adjustment for clinical cardiac risk factors, both anemia (odds ratio [OR] 1.53; 95% confidence interval [CI]: 1.07-2.99) and increased levels of NT-proBNP (OR 4.09; 95% CI: 2.19-7.64) remained independent predictors for postoperative cardiac events. However, increased levels of NT-proBNP were not predictive for the risk of adverse cardiac events in the subgroup of anemic patients (OR 2.16; 95% CI: 0.90-5.21). CONCLUSIONS: Both anemia and NT-proBNP are independently associated with an increased risk for postoperative cardiac events in patients undergoing vascular surgery. NT-proBNP has less predictive value in anemic patients.