Cohort profile of PLUTO: a perioperative biobank focusing on prediction and early diagnosis of postoperative complications.

PURPOSE: Although elective surgery is generally safe, some procedures remain associated with an increased risk of complications. Improved preoperative risk stratification and earlier recognition of these complications may ameliorate postoperative recovery and improve long-term outcomes. The perioperative longitudinal study of complications and long-term outcomes (PLUTO) cohort aims to establish a comprehensive biorepository that will facilitate research in this field. In this profile paper, we will discuss its design rationale and opportunities for future studies. PARTICIPANTS: Patients undergoing elective intermediate to high-risk non-cardiac surgery are eligible for enrolment. For the first seven postoperative days, participants are subjected to daily bedside visits by dedicated observers, who adjudicate clinical events and perform non-invasive physiological measurements (including handheld spirometry and single-channel electroencephalography). Blood samples and microbiome specimens are collected at preselected time points. Primary study outcomes are the postoperative occurrence of nosocomial infections, major adverse cardiac events, pulmonary complications, acute kidney injury and delirium/acute encephalopathy. Secondary outcomes include mortality and quality of life, as well as the long-term occurrence of psychopathology, cognitive dysfunction and chronic pain. FINDINGS TO DATE: Enrolment of the first participant occurred early 2020. During the inception phase of the project (first 2 years), 431 patients were eligible of whom 297 patients consented to participate (69%). Observed event rate was 42% overall, with the most frequent complication being infection. FUTURE PLANS: The main purpose of the PLUTO biorepository is to provide a framework for research in the field of perioperative medicine and anaesthesiology, by storing high-quality clinical data and biomaterials for future studies. In addition, PLUTO aims to establish a logistical platform for conducting embedded clinical trials. TRIAL REGISTRATION NUMBER: NCT05331118.

Leisure-time and occupational physical activity and health outcomes in cardiovascular disease.

OBJECTIVE: In healthy populations, leisure-time physical activity (LTPA) improves health outcomes, while, paradoxically, occupational physical activity (OPA) is associated with detrimental health effects. This study aimed to investigate the associations of LTPA and OPA with mortality, cardiovascular events and type 2 diabetes (T2D) in patients with cardiovascular disease (CVD). METHODS: In 7058 outpatients with CVD (age 61±10 years, 75% male) from the prospective Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease cohort, Cox models were used to quantify the associations between self-reported LTPA and OPA and all-cause mortality, cardiovascular events and T2D. RESULTS: Over 8.6 years (IQR: 4.6-12.5) of follow-up, 1088 vascular events, 1254 deaths and 447 incident T2D cases occurred. The top LTPA quarter had a lower risk of all-cause mortality (HR 0.63, 95% CI 0.54 to 0.74), recurrent cardiovascular events (HR 0.72, 95% CI 0.60 to 0.84) and incident T2D (HR 0.71, 95% CI 0.55 to 0.93), compared with the lowest quarter. The continuous LTPA associations were reverse J-shaped for all-cause mortality and vascular events and linear for T2D. OPA (heavy manual vs sedentary) showed a trend towards an increased risk of all-cause mortality (HR 1.08, 95% CI 0.86 to 1.35), cardiovascular events (HR 1.15, 95% CI 0.91 to 1.45) and T2D (HR 1.04, 95% CI 0.72 to 1.50). The detrimental effects of higher OPA were more pronounced in men, never-smokers, people with higher education and active employment. CONCLUSIONS: In patients with CVD, LTPA was associated with lower risk of all-cause mortality, recurrent cardiovascular events and incident T2D. In contrast, OPA seemed to increase the risk of these outcomes. These findings support the existence of a physical activity paradox in patients with CVD.

Platelet aggregation inhibitor prescription for newly diagnosed peripheral arterial disease in the Netherlands: a cohort study.

OBJECTIVES: Pharmacological treatment of peripheral arterial disease (PAD) comprises of antiplatelet therapy (APT), blood pressure control and cholesterol optimisation. Guidelines provide class-I recommendations on the prescription, but there are little data on the actual prescription practices. Our study provides insight into the prescription of medication among patients with PAD in the Netherlands and reports a 'real-world' patient journey through primary and secondary care. DESIGN: We conducted a cohort study among patients newly diagnosed with PAD between 2010 and 2014. SETTING: Data were obtained from the PHARMO Database Network, a population-based network of electronic pharmacy, primary and secondary healthcare setting records in the Netherlands. The source population for this study comprised almost 1 million individuals. PARTICIPANTS: 'Newly diagnosed' was defined as a recorded International Classification of Primary Care code for PAD, a PAD-specific WCIA examination code or a diagnosis recorded as free text episode in the general practitioner records with no previous PAD diagnosis record and no prescription of P2Y12 inhibitors or aspirin the preceding year. The patient journey was defined by at least 1 year of database history and follow-up relative to the index date. RESULTS: Between 2010 and 2014, we identified 3677 newly diagnosed patients with PAD. Most patients (91%) were diagnosed in primary care. Almost half of all patients (49%) had no APT dispensing record. Within this group, 33% received other anticoagulant therapy (vitamin K antagonist or direct oral anticoagulant). Mono-APT was dispensed as aspirin (40% of patients) or P2Y12 inhibitors (2.5% of patients). Dual APT combining aspirin with a P2Y12 inhibitor was dispensed to 8.5% of the study population. CONCLUSION: Half of all patients with newly diagnosed PAD are not treated conforming to (international) guideline recommendations on thromboembolism prevention through APT. At least 33% of all patients with newly diagnosed PAD do not receive any antithrombotic therapy. Evaluation and improvement of APT prescription and thereby improved prevention of (secondary) cardiovascular events is warranted.

Long-term Outcome of Axillo-axillary Bypass in Patients with Subclavian or Innominate Artery Stenosis.

BACKGROUND: Subclavian or innominate artery stenosis (SAS) may cause upper extremity and cerebral ischemia. In patients with symptomatic subclavian or innominate artery stenosis, percutaneous transluminal angioplasty is the treatment of first choice. When percutaneous transluminal angioplasty is technically restricted or unsuccessful, an extrathoracic bypass grafting, such as an axillo-axillary bypass can be considered. The patency rate of axillo-axillary bypass is often questioned. The aim of this study was to assess long-term outcomes of patients undergoing axillo-axillary bypass for subclavian or innominate artery stenosis (SAS) and to provide a literature overview. METHODS: In this single-center study, data from patients who underwent axillo-axillary bypass for symptomatic SAS between 2002 and 2018 were retrospectively analyzed. Bypass material was Dacron® (54%) or polytetrafluoroethylene (PTFE) (46%). Primary outcome was graft patency and secondary outcome was the occurrence of mortality and stroke. In addition, a systematic literature search was performed in MEDLINE and EMBASE databases including all studies describing patency of axillo-axillary bypass. RESULTS: In total, 28 axillo-axillary bypasses had been performed. Cumulative primary, primary-assisted, and secondary patency rates at one year were 89%, 93%, and 96%, respectively. Cumulative primary, primary-assisted, and secondary patency rates at five years were 76%, 84%, and 87%, respectively. The primary-assisted patency rates at five years for Dacron® and PTFE were 93% and 73%, respectively. A total of four primary axillo-axillary bypass occlusions occurred (14%), with a mean of 12 months (range, 0.4-25) after operation. The 30-day mortality was 7%; one patient died after a stroke and one died of a myocardial infarction. At the first postoperative follow-up control, 22 of the 26 remaining patients (85%) had relief of symptoms. The literature search included 7 studies and described a one-year primary patency range of 93-100% (n = 137) and early postoperative adverse events included death (range, 0-13%) and stroke (range, 0-5%). CONCLUSIONS: Patency rates of axillo-axillary bypasses for patients with a symptomatic SAS are good. However, the procedural complication rate in this series is high and attention should be paid to intervention indication.

Cardiovascular risk factors and the risk of major adverse limb events in patients with symptomatic cardiovascular disease.

AIM: To determine the relationship between non-high-density lipoprotein cholesterol (non-HDL-c), systolic blood pressure (SBP) and smoking and the risk of major adverse limb events (MALE) and the combination with major adverse cardiovascular events (MALE/MACE) in patients with symptomatic vascular disease. METHODS: Patients with symptomatic vascular disease from the Utrecht Cardiovascular Cohort - Secondary Manifestations of ARTerial disease (1996-2017) study were included. The effects of non-HDL-c, SBP and smoking on the risk of MALE were analysed with Cox proportional hazard models stratified for presence of peripheral artery disease (PAD). MALE was defined as major amputation, peripheral revascularisation or thrombolysis in the lower limb. RESULTS: In 8139 patients (median follow-up 7.8 years, IQR 4.0-11.8), 577 MALE (8.7 per 1000 person-years) and 1933 MALE/MACE were observed (29.1 per 1000 person-years). In patients with PAD there was no relation between non-HDL-c and MALE, and in patients with coronary artery disease (CAD), cerebrovascular disease (CVD) or abdominal aortic aneurysm (AAA) the risk of MALE was higher per 1 mmol/L non-HDL-c (HR 1.14, 95% CI 1.01 to 1.29). Per 10 mm Hg SBP, the risk of MALE was higher in patients with PAD (HR 1.06, 95% CI 1.01 to 1.12) and in patients with CVD/CAD/AAA (HR 1.15, 95% CI 1.08 to 1.22). The risk of MALE was higher in smokers with PAD (HR 1.45, 95% CI 0.97 to 2.14) and CAD/CVD/AAA (HR 7.08, 95% CI 3.99 to 12.57). CONCLUSIONS: The risk of MALE and MALE/MACE in patients with symptomatic vascular disease differs according to vascular disease location and is associated with non-HDL-c, SBP and smoking. These findings confirm the importance of MALE as an outcome and underline the importance of risk factor management in patients with vascular disease.

Factors Associated with Hospital Dependent Delay to Carotid Endarterectomy in the Dutch Audit for Carotid Interventions.

OBJECTIVES: As the risk of a recurrent neurological event in patients with symptomatic carotid stenosis requiring carotid endarterectomy (CEA) is highest in the early phase after the first neurological event, guidelines recommend operating on these patients as soon as possible or at least within 14 days of their initial event. However, in real world practice this is often not met. The aim of this study is to identify factors that cause hospital dependent delay to CEA. METHODS: All consecutive patients with symptomatic carotid stenosis undergoing CEA registered in the mandatory Dutch Audit for Carotid Interventions from January 2014 up to and including December 2017 were included in the current analysis. Univariable followed by multivariable logistic regression was used to identify independent factors associated with hospital dependent waiting time, defined as time from the first consultation at any hospital to CEA of more than 14 days. RESULTS: A total of 8620 patients were included. The median time to CEA was 11 days (IQR 8-14). Seventy-eight per cent of patients underwent CEA within 14 days of first hospital consultation. Factors associated with a hospital dependent waiting time longer than 14 days were age (OR 0.99 per year, 95% CI 0.98-0.99), any previous CEA (OR 1.67, 95% CI 1.32-2.09), ocular symptoms as index event (OR 1.31, 95% CI 1.15-1.50), and indirect referral (OR 1.53, 95% CI 1.34-1.73). Hospital surgical volume was not identified as a factor for delay, except for the delay of indirectly referred patients where high volume hospitals reported the shortest delay. CONCLUSION: This cohort derived from a validated nationwide prospective audit identified younger age, previous CEA, ocular symptoms, and indirect referral as hospital dependent factors for delay. High volume hospitals had a similar hospital dependent waiting time to middle and low volume hospitals. However, high volume hospitals had more indirect referrals, implying that their logistics are more efficiently organised.

Heterogeneity in Standard Operating Procedures for Catheter Directed Thrombolysis for Peripheral Arterial Occlusions in The Netherlands: A Nationwide Overview.

OBJECTIVE: Catheter directed thrombolysis (CDT) for acute arterial occlusions of the lower extremities is associated with a risk of major bleeding complications. Strict monitoring of vital functions is advised for timely adjustment or discontinuation of thrombolytic treatment. Nevertheless, current evidence on the optimal application of CDT and use of monitoring during CDT is limited. In this study the different standard operating procedures (SOPs) for CDT in Dutch hospitals were compared against a national guideline in a nationwide analysis. METHODS: SOPs, landmark studies, and national and international guidelines for CDT for acute lower extremity arterial occlusions were compared. The protocols of 34 Dutch medical centres where CDT is performed were assessed. Parameters included contraindications to CDT, co-administration of heparin, thrombolytic agent administration, angiographic control, and patient monitoring. RESULTS: Thirty-four SOPs were included, covering 94% of medical centres performing CDT in the Netherlands. None of the SOPs had identical contraindications and a strong divergence in relative and absolute grading was found. Heparin and urokinase dosages differed by a factor of five. In 18% of the SOPs heparin co-administration was not mentioned. Angiographic control varied between once every 6 h to once every 24 h. In 76% of the SOPs plasma fibrinogen levels were used for CDT dose adjustments. However, plasma fibrinogen level threshold values for treatment adjustments varied between 2.0 g/L and 0.5 g/L. CONCLUSION: The SOPs for CDT for acute arterial occlusions of the lower extremities differ greatly on five major operating aspects among medical centres in the Netherlands. None of the SOPs exactly conforms to current national or international guidelines. This study provides direction on how to increase homogeneity in guideline recommendations and to improve guideline adherence in CDT.

[When is carotid endarterectomy actually indicated for stenosis?] / Wie moet er eigenlijk nog aan vernauwing in de A. carotis geopereerd worden?

Criteria for carotid endarterectomy are based on the results of clinical trials that were conducted more than two decades ago. In the meantime medical treatment has improved, and surgery can be performed more safely. As such, it is currently unknown which patients should be recommended to undergo carotid surgery. The aim of the currently running European Carotid Surgery Trial 2 is to find better answers to this dilemma.

[Faster wound healing after vascular surgery: negative pressure wound therapy for exposed prosthetic vascular grafts in the groin]. / Snellere wondgenezing na vaatchirurgie.

Vascular surgery in the groin is highly susceptible to wound infection (up to about 30%). Wound infections associated with exposed vascular prosthetic grafts are difficult to treat and may lead to acute bleeding or graft failure, requiring amputation of the lower limb in extreme cases. Negative pressure wound therapy is a method to promote wound healing in case of infected vascular grafts. Since there is suspected risk of bleeding, this technique has been adapted with a double-sponge technique in combination with lower negative pressure.

Unexpected Cardiac Computed Tomography Findings in Patients With Postoperative Myocardial Injury.

BACKGROUND: Postoperative myocardial injury (PMI) is a strong predictor of mortality after noncardiac surgery. PMI is believed to be attributable to coronary artery disease (CAD), yet its etiology is largely unclear. We aimed to quantify the prevalence of significant CAD in patients with and without PMI using coronary computed tomography angiography (CCTA). METHODS: This prospective cohort study included patients of 60 years or older without a history of cardiac disease and with and without PMI after intermediate- to high-risk noncardiac surgery. PMI was defined as any serum troponin I level ≥60 ng/L on the first 3 postoperative days. Main exclusion criteria were known cardiac disease and postoperative ischemic symptoms or electrocardiography abnormalities. Noninvasive imaging consisted of a postoperative CCTA. Main outcome was CAD defined as >50% coronary stenosis on CCTA. RESULTS: The analysis included 66 patients. Median peak troponin levels in the PMI (n = 46) and control group (n = 20) were 150 (interquartile range, 120-298) vs 15 (interquartile range, 10-31) ng/L (P < .01). CAD was found in 23 patients with PMI (50%) vs 3 without PMI (15%; relative risk, 3.3; 95% confidence interval, 1.1-9.8). Remarkably, pulmonary embolism was present in 15 patients with PMI (33%) versus in 4 without PMI (20%; relative risk, 1.6; 95% confidence interval, 0.6-4.3). None of the patients died within 30 days. CONCLUSIONS: In patients without a history of cardiac disease, PMI after noncardiac surgery was associated with CAD. In addition, a clinically silent pulmonary embolism was found in one-third of patients with PMI. This urges further research to improve clinical workup using imaging and may have important clinical implications.

Expert review on the VenaSeal® system for endovenous cyano-acrylate adhesive ablation of incompetent saphenous trunks in patients with varicose veins.

INTRODUCTION: The treatment of incompetent truncal veins has been innovated by the introduction of minimally invasive non-thermal non-tumescent (NTNT) techniques. One of these consists of the use of cyanoacrylate glue to occlude the vein lumen by means of the VenaSeal device. Areas covered: This expert-review aims to evaluate NTNT ablation of incompetent saphenous trunks using the VenaSeal device. Expert commentary: Cyanoacrylate adhesive embolization of incompetent truncal veins using the VenaSeal device is a safe and efficacious innovative technique. Further studies are needed to evaluate anatomical and clinical outcomes at long term.

The effect of P2Y12 inhibition on platelet activation assessed with aggregation- and flow cytometry-based assays.

Patients on P2Y12 inhibitors may still develop thrombosis or bleeding complications. Tailored antiplatelet therapy, based on platelet reactivity testing, might reduce these complications. Several tests have been used, but failed to show a benefit of tailored antiplatelet therapy. This could be due to the narrowness of current platelet reactivity tests, which are limited to analysis of platelet aggregation after stimulation of the adenosine diphosphate (ADP)-pathway. However, the response to ADP does not necessarily reflect the effect of P2Y12 inhibition on platelet function in vivo. Therefore, we investigated whether measuring platelet reactivity toward other physiologically relevant agonists could provide more insight in the efficacy of P2Y12 inhibitors. The effect of in vitro and in vivo P2Y12 inhibition on αIIbß3-activation, P-selectin and CD63-expression, aggregate formation, release of alpha, and dense granules content was assessed after stimulation of different platelet activation pathways. Platelet reactivity measured with flow cytometry in 72 patients on P2Y12 inhibitors was compared to VerifyNow results. P2Y12 inhibitors caused strongly attenuated platelet fibrinogen binding after stimulation with peptide agonists for protease activated receptor (PAR)-1 and -4, or glycoprotein VI ligand crosslinked collagen-related peptide (CRP-xl), while aggregation was normal at high agonist concentration. P2Y12 inhibitors decreased PAR-agonist and CRP-induced dense granule secretion, but not alpha granule secretion. A proportion of P2Y12-inhibitor responsive patients according to VerifyNow, displayed normal fibrinogen binding assessed with flow cytometry after stimulation with PAR-agonists or CRP despite full inhibition of the response to ADP, indicating suboptimal platelet inhibition. Concluding, measurement of platelet fibrinogen binding with flow cytometry after stimulation of thrombin- or collagen receptors in addition to ADP response identifies different patients as nonresponders to P2Y12 inhibitors, compared to only ADP-induced aggregation-based assays. Future studies should investigate the value of both assays for monitoring on-treatment platelet reactivity.

Clinical Experience amongst Surgeons in the Asymptomatic Carotid Surgery Trial-1.

INTRODUCTION: Hospital volume may influence the outcomes of carotid revascularization, but in trials the effect of the clinical experience of individual surgeons on procedural outcome is less certain. We assessed perioperative event rates amongst centers with different trial entry volumes and also the effects of individual operator experience in the first Asymptomatic Carotid Surgery Trial-1 (ACST-1). METHODS: In 126 centers participating in ACST-1, surgeons were classified according to their in-trial experience (group A: 50 cases; group B: 51-100 cases; group C: >100 cases), center enrolment volume (group I: <30 patients; group II: 30-75 patients; group III: >75 patients) and center annual hospital volume (group 1: <40 carotid endarterectomies (CEAs); group 2: 40-75 CEAs; group 3: >75 cases). Differences in perioperative event rates were compared using logistic regression analysis. RESULTS: In centers with the most clinical experience compared with those with least experience (groups C vs. A), the number of strokes or deaths was 8 of 275 (2.9%) versus 24 of 810 (3.0%) with OR 0.99 (95% CI 0.44-2.25, p = 0.986). Numbers of strokes or death in high enrolment centers compared with those in low enrolment centers (groups III vs. I) was 20 of 680 (2.9%) versus 21 of 580 (3.6%) with OR 0.81 (95% CI 0.43-1.51, p = 0.921). In centers with a high annual volume compared with those of low annual volume (groups 3 vs. 1), numbers of strokes and death were non-significantly lower, 26 of 823 (3.2%) versus 19 of 422 (4.5%) with OR 0.68 (95% CI 0.37-1.26, p = 0.386). Cumulative stroke risk at 5 and 10 years were similar among different levels of reported clinical experience, enrolment volume and annual hospital volume. CONCLUSION: Although our data did not demonstrate an association between perioperative complications and operators' experience, enrolment volume or annual hospital volume, rates of stroke or death were numerically lower in both high enrolment and high annual volume centers. This lack of association could be explained by an overall low procedural risk in ACST-1.

One-Year Mortality, Causes of Death, and Cardiac Interventions in Patients with Postoperative Myocardial Injury.

BACKGROUND: To evaluate the role of routine troponin surveillance in patients undergoing major noncardiac surgery, unblinded screening with cardiac consultation per protocol was implemented at a tertiary care center. In this study, we evaluated 1-year mortality, causes of death, and consequences of cardiac consultation of this protocol. METHODS: This observational cohort included 3224 patients ≥60 years old undergoing major noncardiac surgery. Troponin I was measured routinely on the first 3 postoperative days. Myocardial injury was defined as troponin I >0.06 µg/L. Regression analysis was used to determine the association between myocardial injury and 1-year mortality. The causes of death, the diagnoses of the cardiologists, and interventions were determined for different levels of troponin elevation. RESULTS: Postoperative myocardial injury was detected in 715 patients (22%) and was associated with 1-year all-cause mortality (relative risk [RR] 1.4, P = 0.004; RR 1.6, P < 0.001; and RR 2.2, P < 0.001 for minor, moderate, and major troponin elevation, respectively). Cardiac death within 1 year occurred in 3%, 5%, and 11% of patients, respectively, in comparison with 3% of the patients without myocardial injury (P = 0.059). A cardiac consultation was obtained in 290 of the 715 patients (41%). In 119 (41%) of these patients, the myocardial injury was considered to be attributable to a predisposing cardiac condition, and in 111 patients (38%), an intervention was initiated. CONCLUSIONS: Postoperative myocardial injury was associated with an increased risk of 1-year all-cause but not cardiac mortality. A cardiac consultation with intervention was performed in less than half of these patients. The small number of interventions may be explained by a low suspicion of a cardiac etiology in most patients and lack of consensus for standardized treatment in these patients.

The Mechanism of Procedural Stroke Following Carotid Endarterectomy within the Asymptomatic Carotid Surgery Trial 1.

INTRODUCTION: Understanding the pathophysiological mechanism of procedural stroke during carotid intervention may help reduce the risk of stroke in those undergoing surgery. We therefore studied the features of procedural strokes within the first Asymptomatic Carotid Surgery Trial-1 (ACST-1) to identify the underlying pathophysiological mechanism. METHODS: In ACST-1, 3,120 patients with severe asymptomatic carotid stenosis thought suitable for surgery were randomized to CEA or indefinite deferral of surgery. Information on procedural (within 30 days) stroke type, laterality, severity and timing was collected. Eight possible mechanisms were defined: embolism from the carotid artery, haemodynamic, thrombosis or occlusion of the carotid artery, hyperperfusion syndrome, cardioembolic, either carotid embolic or haemodynamic, either carotid embolic or thrombotic occlusion, or undetermined. RESULTS: Procedural strokes occurred in 53 patients (2.7%). Strokes were predominantly ischaemic (n = 43; 81%), ipsilateral to the treated artery (n = 42; 79%), often occurred on the day of the operation (n = 32; 60%) and in over half the patients, were disabling or fatal (n = 27; 51%). The identified stroke mechanism was carotid embolic (n = 7), haemodynamic (n = 5), thrombosis or occlusion of the carotid artery (n = 9), hyperperfusion (n = 7), cardioembolic (n = 3), 'probably carotid embolic or haemodynamic' (n = 7), 'probably carotid embolic or thrombotic occlusion' (n = 3) and undetermined in 12 cases. CONCLUSION: In ACST-1, the risk of procedural stroke was low. Most strokes (60%) occurred on the day of the procedure and were caused by thrombosis or thrombotic occlusion of the ipsilateral carotid artery. These findings emphasize the importance of immediate assessment of the treated carotid artery when a stroke occurs after CEA.

Percutaneous Transluminal Angioplasty and Drug-Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia (PADI) Trial.

BACKGROUND: Endovascular infrapopliteal treatment of patients with critical limb ischemia using percutaneous transluminal angioplasty (PTA) and bail-out bare metal stenting (BMS) is hampered by restenosis. In interventional cardiology, drug-eluting stents (DES) have shown better patency rates and are standard practice nowadays. An investigator-initiated, multicenter, randomized trial was conducted to assess whether DES also improve patency and clinical outcome of infrapopliteal lesions. METHODS AND RESULTS: Adults with critical limb ischemia (Rutherford category ≥4) and infrapopliteal lesions were randomized to receive PTA±BMS or DES with paclitaxel. Primary end point was 6-month primary binary patency of treated lesions, defined as ≤50% stenosis on computed tomographic angiography. Stenosis >50%, retreatment, major amputation, and critical limb ischemia-related death were regarded as treatment failure. Severity of failure was assessed with an ordinal score, ranging from vessel stenosis through occlusion to the clinical failures. Seventy-four limbs (73 patients) were treated with DES and 66 limbs (64 patients) received PTA±BMS. Six-month patency rates were 48.0% for DES and 35.1% for PTA±BMS (P=0.096) in the modified-intention-to-treat and 51.9% and 35.1% (P=0.037) in the per-protocol analysis. The ordinal score showed significantly worse treatment failure for PTA±BMS versus DES (P=0.041). The observed major amputation rate remained lower in the DES group until 2 years post-treatment, with a trend toward significance (P=0.066). Less minor amputations occurred after DES until 6 months post-treatment (P=0.03). CONCLUSIONS: In patients with critical limb ischemia caused by infrapopliteal lesions, DES provide better 6-month patency rates and less amputations after 6 and 12 months compared with PTA±BMS. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00471289.

The use of platelet reactivity testing in patients on antiplatelet therapy for prediction of bleeding events after cardiac surgery.

Many patients are treated with platelet inhibitors such as aspirin and clopidogrel for prevention of thrombotic cardiovascular events. However, the inhibitory effect of antiplatelet therapy is variable between patients; in some, the platelets are hardly inhibited, while in others, the platelets are excessively inhibited. The newer and more potent platelet inhibitors, prasugrel and ticagrelor, often lead to low platelet reactivity, which potentially leads to bleeding events. Preoperative measurement of platelet reactivity in patients receiving platelet inhibitors who undergo cardiac surgery, could be useful to identify those with low platelet reactivity and thus have an increased risk of bleeding during or after surgery. In this review, we discuss the most commonly used platelet inhibitors and platelet function tests. Furthermore, we will provide an overview of the evidence for the prediction of post-operative bleeding at the operation site with preoperative platelet reactivity testing in patients undergoing cardiac surgery.

Cause-specific mortality and years of life lost in patients with different manifestations of vascular disease.

BACKGROUND: Patients with cardiovascular disease might be at increased risk of non-vascular mortality due to shared risk factors. Our aim was to evaluate causes of death and years of life lost (YLL) in patients with different manifestations of vascular disease. DESIGN: The design was a prospective cohort study. METHODS: A total of 5911 patients with stable coronary artery disease, cerebrovascular disease, peripheral artery disease (PAD), abdominal aortic aneurysm or polyvascular disease were followed-up for mortality. Cause-specific standardised mortality ratios (SMRs) and YLL, compared to the Dutch population, were estimated. Determinants for cause-specific mortality were evaluated using competing risks models. RESULTS: During a median follow-up of 6.0 years (interquartile range (IQR): 3.1-9.2), 958 (16.2%) patients died. All-cause mortality was increased compared to the general population (SMR: 1.26, 95% confidence interval (CI): 1.18-1.34). Patients with PAD and polyvascular disease were at highest risk, especially for ischaemic heart disease (SMR: 2.52, 95% CI: 1.70-3.60 and SMR: 3.97, 95% CI: 3.18-4.90, respectively). Patients with PAD were at increased risk of dying from cancer (SMR: 1.67, 95% CI: 1.25-2.17). On average, patients with vascular disease of ≥50 years died 7.8 years younger than the general population, with 80% of the excess YLL attributable to cardiovascular disease. In middle-aged patients the excess YLL were about 10 years, of which 24% were lost due to cancer. Important determinants for mortality were male gender, smoking, physical inactivity, renal insufficiency and polyvascular disease. CONCLUSIONS: Patients with manifest vascular disease are at increased risk of both cardiovascular and cancer mortality, particularly patients with PAD or polyvascular disease. On average, patients with vascular disease of ≥50 years die 7.8 years younger than the general population.