Peripheral arterial disease (PAD) - A challenging manifestation of atherosclerosis.

The diagnosis of peripheral arterial disease (PAD) is not always evident as symptoms and signs may show great variation. As all grades of PAD are linked to both an increased risk for cardiovascular complications and adverse limb events, awareness of the condition and knowledge about diagnostic measures, prevention and treatment is crucial. This article presents in a condensed form information on PAD and its management.

Myocardial infarction and peripheral arterial disease: Treatment patterns and long-term outcome in men and women results from a Swedish nationwide study.

BACKGROUND: Differences in comorbidity, pharmacotherapy, cardiovascular (CV) outcome, and mortality between myocardial infarction (MI) patients and peripheral arterial disease (PAD) patients are not well documented. AIM: The aim of this study was to compare comorbidity, treatment patterns, CV outcome, and mortality in MI and PAD patients, focusing on sex differences. METHODS: This observational, population-based study used data retrieved from mandatory Swedish national registries. The risks of MI and death were assessed by Kaplan-Meier analysis. Secondary preventive drug use was characterized. Cox proportional risk hazard modelling was used to determine the risk of specific events. RESULTS: Overall, 91,808 incident MI patients and 52,408 PAD patients were included. CV mortality for MI patients at 12, 24, and 36 months after index was 12.3%, 19.3%, and 25.4%, and for PAD patients it was 15.5%, 23.4%, and 31.0%. At index, 89% of MI patients and 65% of PAD patients used aspirin and 74% and 53%, respectively, used statins. Unlike MI women, women with PAD had a lower rate of other CV-related comorbidities and a lower risk of CV events (age-adjusted hazard ratio 0.81, 95% confidence interval 0.79‒0.84), CV death (0.78, 0.75‒0.82), and all-cause death (0.78, 0.76‒0.80) than their PAD male counterparts. CONCLUSION: PAD patients were less intensively treated and had a higher CV mortality than MI patients. Women with PAD were less likely than men to present with established polyvascular disease, whereas the opposite was true of women with MI. This result indicates that the lower-limb vasculature may more often be the index site for atherosclerosis in women.

Leukocyte subsets and abdominal aortic aneurysms detected by screening in men.

OBJECTIVE: In the present case-control study, we describe the associations between leukocyte subsets in blood and early, screening-detected AAA in men. An abdominal aortic aneurysm (AAA) may result in a life-threatening rupture of the aortic wall. The trigger for AAA formation remains unknown, but the vascular adventitia of advanced AAAs is infiltrated by various leukocytes, indicating that the pathogenesis may involve inflammation. METHODS: In Sweden, all 65-year-old men are invited to an ultrasound examination for detection of AAA. At the Gothenburg screening site, 16 256 men were examined in 2013-2017, 1.2% of whom had an AAA (diameter of the infrarenal aorta ≥30 mm). All men with AAA at screening as well as a randomized selection of AAA-free screened men were invited to participate in a case-control study. RESULTS: The median diameter of AAAs was 33 mm. Men with an AAA (n = 151) had a higher frequency of smoking, hypertension and statin use than controls (n = 224). Blood levels of neutrophils, lymphocytes, monocytes and basophils were higher in individuals with an AAA, but eosinophil count did not differ from controls. Odds ratios (95% confidence interval) for AAA were 8.6 (4.2-17.4), 3.5 (1.9-6.6) and 3.3 (1.8-6.3) for the highest versus lowest quartile of neutrophils, lymphocytes and monocytes, respectively. For neutrophils and lymphocytes, the association with AAA remained significant after adjustment for smoking and other known risk factors/markers. CONCLUSION: Several, but not all, subsets of circulating leukocytes are associated with screening-detected AAA in men, which is insufficiently explained by associations with smoking and other confounders.

Cost-effectiveness of revascularization in patients with intermittent claudication.

BACKGROUND: Revascularization is a treatment option for patients with intermittent claudication. However, there is a lack of evidence to support its long-term benefits and cost-effectiveness. The aim of this study was to compare the cost-effectiveness of revascularization and best medical therapy (BMT) with that of BMT alone. METHODS: Data were used from the IRONIC (Invasive Revascularization Or Not in Intermittent Claudication) RCT where consecutive patients with mild-to-severe intermittent claudication owing to aortoiliac or femoropopliteal disease were allocated to either BMT alone (including a structured, non-supervised exercise programme) or to revascularization together with BMT. Inpatient and outpatient costs were obtained prospectively over 24 months of follow-up. Mean improvement in quality-adjusted life-years (QALYs) was calculated based on responses to the EuroQol Five Dimensions EQ-5D-3 L™ questionnaire. Cost-effectiveness was assessed as the cost per QALY gained. RESULTS: A total of 158 patients were randomized, 79 to each group. The mean cost per patient in the BMT group was €1901, whereas it was €8280 in the group treated with revascularization in addition to BMT, with a cost difference of €6379 (95 per cent c.i. €4229 to 8728) per patient. Revascularization in addition to BMT resulted in a mean gain in QALYs of 0·16 (95 per cent c.i. 0·06 to 0·24) per patient, giving an incremental cost-effectiveness ratio of €42 881 per QALY. CONCLUSION: The costs associated with revascularization together with BMT in patients with intermittent claudication were about four times higher than those of BMT alone. The incremental cost-effectiveness ratio of revascularization was within the accepted threshold for public willingness to pay according to the Swedish National Guidelines, but exceeded that of the UK National Institute for Health and Care Excellence guidelines.

Amputation Rates, Mortality, and Pre-operative Comorbidities in Patients Revascularised for Intermittent Claudication or Critical Limb Ischaemia: A Population Based Study.

OBJECTIVES: The aims of this population based study were to describe mid- to long-term amputation risk, cumulative incidence of death or amputation, and differences in pre-operative comorbidities in patients revascularised for lower limb peripheral artery disease (PAD). METHODS: This was an observational cohort study. Data from the Swedish National Quality Registry for Vascular Surgery (Swedvasc) were combined with mandatory national health care registries and patient medical records. All patients who underwent revascularisation in Sweden between May 2008 and May 2013 for intermittent claudication (IC) or critical limb ischaemia (CLI), aged 50 years and older, were identified through the Swedvasc database. The mandatory national health care registries and medical records provided data on comorbidities, mortality, and major amputations. RESULTS: A total of 16,889 patients with PAD (IC, n = 6272; CLI, n = 10,617) were studied. The incidence of amputations in IC patients was 0.4% (range 0.3%-0.5%) per year. Among CLI patients, the amputation rate during the first 6 months following revascularisation was 12.0% (95% CI 11.3-12.6). Thereafter, the incidence declined to approximately 2% per year. The cumulative combined incidence of death or amputation 3 years after revascularisation was 12.9% (95% CI 12.0-13.9) in IC patients and 48.8% (95% CI 47.7-49.8) in CLI patients. Among CLI patients, compared with IC patients, the prevalence of diabetes, ischaemic stroke, heart failure, and atrial fibrillation was approximately doubled and renal failure was nearly tripled, even after age standardisation. CONCLUSION: The risk of amputation is particularly high during the first 6 months following revascularisation for CLI. IC patients have a benign course in terms of limb loss. Mortality in both IC and CLI patients is substantial. Revascularised CLI patients have different comorbidities from IC patients.

Assessment of Minimum Important Difference and Substantial Clinical Benefit with the Vascular Quality of Life Questionnaire-6 when Evaluating Revascularisation Procedures in Peripheral Arterial Disease.

OBJECTIVES: Patient reported outcomes are increasingly used to assess outcomes after peripheral arterial disease (PAD) interventions. VascuQoL-6 (VQ-6) is a PAD specific health-related quality of life (HRQoL) instrument for routine clinical practice and clinical research. This study assessed the minimum important difference for the VQ-6 and determined thresholds for the minimum important difference and substantial clinical benefit following PAD revascularisation. MATERIALS AND METHODS: This was a population-based observational cohort study. VQ-6 data from the Swedvasc Registry (January 2014 to September 2016) was analysed for revascularised PAD patients. The minimum important difference was determined using a combination of a distribution based and an anchor-based method, while receiver operating characteristic curve analysis (ROC) was used to determine optimal thresholds for a substantial clinical benefit following revascularisation. RESULTS: A total of 3194 revascularised PAD patients with complete VQ-6 baseline recordings (intermittent claudication (IC) n = 1622 and critical limb ischaemia (CLI) n = 1572) were studied, of which 2996 had complete VQ-6 recordings 30 days and 1092 a year after the vascular intervention. The minimum important difference 1 year after revascularisation for IC patients ranged from 1.7 to 2.2 scale steps, depending on the method of analysis. Among CLI patients, the minimum important difference after 1 year was 1.9 scale steps. ROC analyses demonstrated that the VQ-6 discriminative properties for a substantial clinical benefit was excellent for IC patients (area under curve (AUC) 0.87, sensitivity 0.81, specificity 0.76) and acceptable in CLI (AUC 0.736, sensitivity 0.63, specificity 0.72). An optimal VQ-6 threshold for a substantial clinical benefit was determined at 3.5 scale steps among IC patients and 4.5 in CLI patients. CONCLUSIONS: The suggested thresholds for minimum important difference and substantial clinical benefit could be used when evaluating VQ-6 outcomes following different interventions in PAD and in the design of clinical trials.

Weak Links in the Early Chain of Care of Acute Lower Limb Ischaemia in Terms of Recognition and Emergency Management.

OBJECTIVES: Acute lower limb ischaemia (ALLI) is a potentially fatal, limb threatening medical emergency. Early treatment is essential for a good outcome. The aim was to describe the early chain of care in ALLI focusing on lead times and emergency management in order to identify weak links for improvement. METHODS: This was a retrospective, descriptive case study. This study analysed the medical records of all patients with a main discharge diagnosis of ALLI between January 2009 and December 2014. Predetermined emergency care data on lead times, diagnosis recognition, presenting symptoms, emergency care treatment and outcome were collected for patients who were transported by the Emergency Medical Service (EMS) and those who were not. RESULTS: In total, 552 medical records were audited of which 195 patients fulfilled the inclusion criteria and were analysed. Among them were 117 (60%) transported by the EMS. The median time from symptom onset to revascularisation was 23 (interquartile range [IQR] 10-55; EMS transported) and 93 (IQR 42-152, not EMS transported) hours (p < .01). The time from symptom onset to arrival in hospital was 5 (IQR 2-26; EMS transported) and 48 (IQR 6-108; not EMS transported) hours. After arrival in hospital, the median time to first doctor evaluation was 51 (IQR 28-90; EMS transported) and 80 (IQR 44-169; not EMS transported) minutes, p = .01. Low molecular weight heparin (LMWH) was given to 72% of patients in the emergency department (ED) and a multivariate analysis showed that the use of LMWH was associated with a more favourable outcome. CONCLUSIONS: Both the time spent in the ED and the time from the onset of symptoms to revascularisation were considerably longer than optimal. Time delays in the early treatment chain can mainly be attributed to "patient delay" and a considerable time spent in hospital before revascularisation. The use of LMWH as an integral part of ED management was associated with a better outcome.

The Impact of Initial Misdiagnosis of Ruptured Abdominal Aortic Aneurysms on Lead Times, Complication Rate, and Survival.

OBJECTIVE/BACKGROUND: To investigate the frequency of initial misdiagnosis and the clinical consequences of an initial misdiagnosis of ruptured abdominal aortic aneurysms (rAAA). METHODS: This was a retrospective cohort study. Data from the Swedish National Registry for Vascular Surgery (Swedvasc) and medical charts were extracted for patients treated for rAAA in the West of Sweden in the period 2008-14. Initially misdiagnosed patients were compared with correctly diagnosed patients. RESULTS: In all, 261 patients were included in the study. Patients with rAAA were initially misdiagnosed in 33% (n = 86) of the cases and this caused a 4.8 hour (median time) additional delay to surgical intervention. There were no differences in 30 day mortality between initially misdiagnosed patients and correctly diagnosed patients (27.9% vs. 28.0%; p = 1.00). The adjusted odds ratio for mortality in initially misdiagnosed patients compared with correctly diagnosed patients was 0.78 (95% confidence interval 0.38-1.60). No difference was observed between the groups regarding 90 day mortality, length of intensive care, need for post-operative ventilator support, need of haemodialysis support, and length of hospital stay. CONCLUSION: Misdiagnosis is common in patients with rAAA, and treatment is significantly delayed in misdiagnosed patients. The study did not show any survival disadvantage or increased frequency of post-operative complications in misdiagnosed patients despite the delayed treatment. However, only patients who reached surgical intervention were included in the analysis.

Two-year results from a randomized clinical trial of revascularization in patients with intermittent claudication.

BACKGROUND: Intermittent claudication is associated with significant impairment of health-related quality of life. The use of revascularization techniques to improve health-related quality of life remains controversial. METHODS: Patients with intermittent claudication due to iliac or femoropopliteal peripheral artery disease were enrolled in the IRONIC trial. They were randomized to either best medical therapy (BMT), including a structured, non-supervised exercise programme, or revascularization with either endovascular or open techniques in addition to BMT. The primary outcome was health-related quality of life at 2 years assessed using the Short Form 36 (SF-36(®) ) questionnaire. Secondary outcomes included VascuQoL questionnaire results, treadmill walking distances and achievement of patient-specified treatment goals. RESULTS: Both randomized groups had improved health-related quality of life and treadmill walking distance at 2-year follow-up. Overall SF-36(®) physical component summary score, three SF-36(®) physical domain scores, overall VascuQoL score, and three of five VascuQoL domain scores showed significantly greater improvement in the group that also received invasive treatment. Intermittent claudication distance on a graded treadmill improved more in the revascularization + BMT group (117 versus 55 m; P = 0·003) whereas maximum walking distance and 6-min walk test distance were similar. Some 44 per cent of patients in the revascularization + BMT group reported they had fully achieved their treatment goal versus 10 per cent in the BMT group. CONCLUSION: A revascularization strategy with unsupervised exercise improved health-related quality of life and intermittent claudication distance more than standard BMT and an unsupervised exercise programme in patients with lifestyle-limiting claudication. REGISTRATION NUMBER: NCT01219842 (http://www.clinicaltrials.gov).

Low post-operative mortality after surgery on patients with screening-detected abdominal aortic aneurysms: a Swedvasc registry study.

OBJECTIVES: Screening for abdominal aortic aneurysms (AAAs) substantially reduces aneurysm-related mortality in men and is increasing worldwide. This cohort study compares post-operative mortality and complications in men with screening-detected vs. non-screening-detected AAAs. METHODS: Data were extracted from the Swedish National Registry for Vascular Surgery (Swedvasc) for all screening-detected men treated for AAA (n = 350) and age-matched controls treated for non-screening-detected AAA (n = 350). RESULTS: There were no differences in baseline characteristics besides age, which was lower in the screening-detected group than in the non-screening-detected group (median 66 vs. 68, p < .001). Open repair was used more frequently than endovascular aortic repair (EVAR) in patients with screening-detected AAAs than in non-screening-detected controls (56% vs. 45% p = .005). No differences in major post-operative complications at 30 days were observed between the groups. In patients treated with open repair there were no differences in 30-day, 90-day or 1-year mortality in screening-detected patients compared to non-screening-detected controls (1.0% vs. 3.2% p = .25, 2.1% vs. 4.5% p = .23, 4.1% vs. 5.8% p = .61). None of the patients treated with EVAR in either group died within 30 days. The 90-day mortality after EVAR was lower in patients with screening-detected AAA than in those with non-screening-detected AAAs (0.0% vs. 3.1%, p = .04). No difference in the 1-year mortality was detected in the EVAR-patients between the two groups (1.4% vs. 4.7%, p = .12). CONCLUSIONS: The contemporary post-operative mortality after AAA surgery was low in this national audit of patients with screening-detected AAAs and age-matched controls. Patients with screening-detected AAAs have the same frequency of complications at 30 days as patients with non-screening-detected AAA. This study gives further support to national screening programs for the detection of AAA in men.

Nationwide experience of cardio- and cerebrovascular complications during infrainguinal endovascular intervention for peripheral arterial disease and acute limb ischaemia.

OBJECTIVES: Endovascular treatment for peripheral arterial disease (PAD) is increasingly used and also continuously applied to more severe vascular pathology. Only few studies report on systemic complications during these procedures, but it is important to address these risks. We report the results of a recent national audit on cardio- and cerebrovascular complications after endovascular procedures for PAD. METHODS: Data from the Swedish Vascular Registry (Swedvasc) were retrieved on all infrainguinal endovascular procedures performed between May 2008 and December 2011. A total of 9187 cases were analysed regarding the prevalence of myocardial infarction and major stroke within 30 days post-intervention. A literature review in PubMed and Cochrane databases was conducted. RESULTS: The risk of myocardial infarction was 0.3% in intermittent claudication, 1.2% in critical limb ischaemia and 1% in acute limb ischaemia. Corresponding risk of major stroke was 0.4%, 0.3% and 1.4%. Thrombolytic therapy was associated with a threefold risk of major stroke. Only a few studies relevant to the subject were found during the literature review. CONCLUSIONS: In this population-based study we found a low risk of cardiac complications, but catheter-administered thrombolytic therapy entailed a non-negligible risk of major stroke.

Walking performance and health-related quality of life after surgical or endovascular invasive versus non-invasive treatment for intermittent claudication--a prospective randomised trial.

OBJECTIVES: Despite limited scientific evidence for the effectiveness of invasive treatment for intermittent claudication (IC), revascularisation procedures for IC are increasingly often performed in Sweden. This randomised controlled trial compares the outcome after 2 years of primary invasive (INV) versus primary non-invasive (NON) treatment strategies in unselected IC patients. MATERIALS/METHODS: Based on arterial duplex and clinical examination, IC patients were randomised to INV (endovascular and/or surgical, n = 100) or NON (n = 101). NON patients could request invasive treatment if they deteriorated during follow-up. Primary outcome was maximal walking performance (MWP) on graded treadmill test at 2 years and secondary outcomes included health-related quality of life (HRQL), assessed with Short Form (36) Health Survey (SF-36). RESULTS: MWP was not significantly (p = 0.104) improved in the INV versus the NON group. Two SF-36 physical subscales, Bodily Pain (p < 0.01) and Role Physical (p < 0.05) improved significantly more in the INV versus the NON group. There were 7% crossovers against the study protocol in the INV group. CONCLUSIONS: Although invasive treatment did not show any significant advantage regarding MWP, the HRQL improvements associated with invasive treatment tentatively suggest secondary benefits of this regimen. On the other hand, a primary non-invasive treatment strategy seems to be accepted by most IC patients.

Spontaneous isolated dissection of the celiac trunk with rupture of the proximal splenic artery: a case report.

INTRODUCTION: Spontaneous visceral artery dissection is an uncommon cause of acute abdominal pain. Complications are ischemia, aneurysm formation and rupture. We present a case with synchronous rupture of the splenic artery causing massive bleeding and demanding urgent surgery. To our knowledge, only 24 previous cases are reported in the literature. REPORT: The patient was a 56-year-old male smoker with no previous medical history who was treated surgically with exposure of the suprarenal aorta through left-sided medial visceral rotation and isolation of the celiac artery. The origin of the bleeding was identified as a longitudinal rupture of the splenic artery just distal to the hepatic artery. The artery was ligated and splenectomy was performed because of splenic infarction. The hepatic artery was patent and no reconstruction was needed. The postoperative course was uneventful, treatment with antiplatelets and antihypertensive drugs was initiated. The patient was discharged after ten days and at monthly follow-up the patient was in good condition. CT angiography was performed six months postoperative and the celiac trunk was patent but a small aneurysm had developed. DISCUSSION: Dissection of the celiac artery is uncommon and is rarely considered in the diagnosis of acute abdominal pain. The condition could be mistaken for a ruptured AAA. The condition may be underdiagnosed and it seems likely that more cases will be identified in the future as a result of the rapidly evolving vascular imaging modalities.

New concept in echocardiography: harmonic imaging of tissue without use of contrast agent.

BACKGROUND: Endocardial border detection is important for echocardiographic assessment of left-ventricular function. Second harmonic imaging of contrast agents enhances this border detection. We discovered that harmonic imaging improves tissue visualisation even before contrast injection. We therefore sought objectively to demonstrate the degree of enhancement of endocardial and myocardial visualisation. METHODS: An ATL HDI-3000 scanner with software for contrast harmonic imaging was used to record short-axis images of the left ventricle in 27 patients with possible myocardial disease and 22 controls, in the fundamental mode and with harmonic imaging. A computer program measured the relative grey-scale values within six segments of the endocardium and myocardium. An Acuson Sequoia scanner equipped with software for tissue harmonic imaging was used to investigate the reproducibility of ejection-fraction calculations in 22 patients with ischaemic heart disease. FINDINGS: Harmonic imaging produced brighter endocardium within each segment. Relative to the mean grey value of the total imaging sector, the values for harmonic and fundamental imaging were 171.5 vs 85.6% (p<0.0001) in end diastole and 194.1 vs 106.7% (p<0.0001) in end systole. Results for the myocardial segments were also significantly better for harmonic imaging. Structure enhancement of similar magnitude was seen among patients and healthy controls. Use of harmonic imaging reduced the proportion of unacceptable images by 14-46% in different views and improved the reproducibility of biplane ejection-fraction measurements. INTERPRETATION: In comparison with fundamental imaging, the relative endocardial and myocardial brightness is enhanced by harmonic imaging.