Editor's Choice - Short Term Cost Effectiveness of Radiofrequency Ablation and High Ligation and Stripping for Great Saphenous Vein Incompetence.

OBJECTIVE: Superficial venous incompetence (SVI) is a common disease that causes significant quality of life (QoL) impairment. There is a need for more health economic evaluations of SVI treatment. The aim of this study was to perform a cost effectiveness analysis in patients with great saphenous vein (GSV) incompetence comparing radiofrequency ablation (RFA), high ligation and stripping (HL/S), and no treatment or conservative treatment with one year follow up. METHODS: Randomised controlled trial economic analysis from an ongoing trial; 143 patients (156 limbs) with GSV incompetence (CEAP clinical class 2 - 6) were included. Treatment was performed with RFA or HL/S. Follow up was performed up to one year using duplex ultrasound, revised venous clinical severity score (r-VCSS), Aberdeen Varicose Vein Questionnaire (AVVQ), and EuroQol-5D-3L (EQ-5D-3L). RESULTS: Seventy-eight limbs were treated with RFA and HL/S respectively. No treatment or conservative treatment was assumed to have zero in treatment cost and no treatment benefit. In the RFA group, one limb had reflux in the GSV after one month and three limbs after one year. In HL/S, two limbs had remaining reflux in the treated area at one month and one year. Both disease severity (r-VCSS, p = .004) and QoL (AVVQ, p = .021 and EQ-5D-3L, p = .028) were significantly improved over time. The QALY gain was 0.21 for RFA and 0.17 for HL/S. The cost per patient was calculated as €1 292 for RFA and €2 303 for HL/S. The cost per QALY (compared with no treatment or conservative treatment) was €6 155 for RFA and €13 549 for HL/S. With added cost for days absent from work the cost per QALY was €7 358 for RFA and €24 197 for HL/S. The cost per QALY for both methods was well below the threshold suggested by Swedish National Board of Health. CONCLUSION: RFA is more cost effective than HL/S and no treatment or conservative treatment at one year follow up.

Quantifiable remaining reflux 1 year after treatment of superficial venous incompetence is associated with impaired clinical outcome.

OBJECTIVE: Remaining symptoms after treatment of superficial venous incompetence is a common problem. Duplex ultrasound is often used during follow-up, but does not permit an overall quantification of venous function. We have developed a plethysmographic method using occlusion cuffs for separation of superficial and deep venous reflux. By assessing the superficial component it is possible to quantify a potential suboptimal hemodynamic treatment in patients with superficial venous incompetence. The aim was to examine whether patients with hemodynamically quantifiable remaining reflux after treatment experience impaired clinical outcomes. METHODS: This single-center prospective cohort study evaluated 156 limbs with great saphenous vein incompetence treated with radiofrequency ablation or high ligation and stripping. Duplex ultrasound and strain-gauge plethysmography (SGP) with and without selective superficial occlusion were performed before and one-year after treatment. Time taken (seconds) to reach 50% of the venous volume (T50) was evaluated. A difference in the T50of >5 seconds between postoperative strain-gauge plethysmography with and without superficial occlusion was defined as remaining reflux. The Venous Clinical Severity Score (VCSS) and Aberdeen Varicose Vein Questionnaire (AVVQ) were evaluated and compared between patients with and without remaining reflux. Multivariable logistic regression was used to evaluate risk factors for remaining plethysmographic reflux. RESULTS: In all patients, median (25th, 75th percentile) T50 increased preoperatively from 7 seconds (3, 12 seconds) to 17 seconds (11, 28 seconds) (P < .001) 1 year after treatment. The VCSS and AVVQ were reduced (VCSS, 8.0 [6.0, 10.0] vs 3.0 [1.0, 5.0] [P < .001]; AVVQ, 21.8 [15.8, 32.1] vs 6.4 [2.2, 11.0] [P < .001]). Of the 156 limbs, 87 (56%) demonstrated remaining reflux 1 year after treatment. Patients with remaining plethysmographic reflux displayed higher median (25th, 75th percentile) VCSS (3.0 [2.0, 5.0] vs 2.0 [1.0, 4.0]; P = .012) and AVVQ (7.5 [2.7, 14.9] vs 4.7 [1.6, 9.2]; P = .025). Multivariate logistic regression showed that higher preoperative C in the Clinical Etiology Anatomy Pathophysiology classification (CEAP) (odds ratio [OR], 2.9 [95% confidence interval [CI], 1.34-6.46), age (OR, 1.03; 95% CI, 1.001-1.065), small saphenous vein incompetence (OR, 4.2; 95% CI, 1.30-13.73) and postoperative great saphenous vein reflux below the treated area (OR, 2.16; 95% CI, 1.02-4.56) were significant risk factors for remaining plethysmographic reflux. CONCLUSIONS: A majority of treated limbs showed quantifiable reflux 1 year after intervention and these patients displayed worse patient related outcomes assessed with the VCSS and AVVQ. Remaining plethysmographic reflux was associated with preoperative small saphenous vein incompetence and reflux below the treated area as well as advanced age and higher C in CEAP.

Attrition in the Gothenburg H70 birth cohort studies, an 18-year follow-up of the 1930 cohort.

Background: Longitudinal studies are essential to understand the ageing process, and risk factors and consequences for disorders, but attrition may cause selection bias and impact generalizability. We describe the 1930 cohort of the Gothenburg H70 Birth Cohort Studies, followed from age 70 to 88, and compare baseline characteristics for those who continue participation with those who die, refuse, and drop out for any reason during follow-up. Methods: A population-based sample born 1930 was examined with comprehensive assessments at age 70 (N = 524). The sample was followed up and extended to increase sample size at age 75 (N = 767). Subsequent follow-ups were conducted at ages 79, 85, and 88. Logistic regression was used to analyze baseline characteristics in relation to participation status at follow-up. Results: Refusal to participate in subsequent examinations was related to lower educational level, higher blood pressure, and lower scores on cognitive tests. Both attrition due to death and total attrition were associated with male sex, lower educational level, smoking, ADL dependency, several diseases, poorer lung function, slower gait speed, lower scores on cognitive tests, depressive symptoms, and a larger number of medications. Attrition due to death was also associated with not having a partner. Conclusions: It is important to consider different types of attrition when interpreting results from longitudinal studies, as representativeness and results may be differently affected by different types of attrition. Besides reducing barriers to participation, methods such as imputation and weighted analyses can be used to handle selection bias.

Prediction of Postoperative Delirium After Cardiac Surgery with A Quick Test of Cognitive Speed, Mini-Mental State Examination and Hospital Anxiety and Depression Scale.

Purpose: To evaluate if preoperative assessment with A Quick Test of Cognitive Speed (AQT) could increase the accuracy of predicting delirium after cardiac surgery compared to Mini-Mental State Examination (MMSE), and examine if a composite of variables, including cognitive function and depressive symptoms, could be useful to predict delirium. Patients and Methods: Cardiac surgery was performed in 218 patients (mean age 72 years). Preoperative evaluation involved AQT, MMSE and Hospital Anxiety And Depression Scale (HADS). Postoperative delirium was assessed using Nursing Delirium Screening Scale (Nu-DESC) and Confusion Assessment Method-ICU (CAM-ICU). Logistic regression was performed to detect predictors of postoperative delirium and receiver operator characteristic curves (ROC) with area under the curve (AUC) to determine the accuracy. Results: Postoperative delirium occurred in 47 patients (22%) who had lower MMSE scores (median (range), 27 (19-30) vs 28 (20-30), p=0.009) and slower AQT (median (range), 76 (48-181) vs 70 (40-182) seconds, p=0.030) than patients without delirium. Predictive power measured as AUC (95% CI) was 0.605 (0.51-0.70) for AQT and 0.623 (0.53-0.72) for MMSE. Logistic regression (OR, 95% CI) showed MMSE <27 points (2.72, 1.27-5.86), AQT >70 sec (2.26, 1.03-4.95), HADS-D >4 points (2.60, 1.21-5.58) and longer cardiopulmonary bypass-time (1.007, 1.002-1.013) to be associated with postoperative delirium. Combining these parameters yielded an AUC of 0.736 (0.65-0.82). Conclusion: The ability of predicting delirium using AQT was similar to MMSE, and only slightly higher by combining AQT and MMSE. Adding HADS-D and cardiopulmonary bypass-time to MMSE and AQT increased the predictive power to a borderline acceptable discriminatory value. Preoperative cognitive tests and screening for depressive symptoms may help identify patients at risk of postoperative delirium. Yet, there is still a need to establish useful preoperative tests.

Slowing gait speed precedes cognitive decline by several years.

INTRODUCTION: In this longitudinal study, we aimed to examine if slowing gait speed preceded cognitive decline and correlated with brain amyloidosis. METHODS: The sample (n = 287) was derived from the Gothenburg H70 Birth Cohort Studies, with follow-ups between 2000 and 2015. Gait speed was measured by indoor walk, and cognition using the Clinical Dementia Rating (CDR) score. All participants had CDR = 0 at baseline. Some participants had data on cerebrospinal fluid (CSF) amyloid beta (Aß)1-42 concentrations at the 2009 examination. RESULTS: Gait speed for participants who worsened in CDR score during follow-up was slower at most examinations. Baseline gait speed could significantly predict CDR change from baseline to follow-up. Subjects with pathological CSF Aß1- 42 concentrations at the 2009 visit had lost more gait speed compared to previous examinations. DISCUSSION: Our results indicate that gait speed decline precedes cognitive decline, is linked to Alzheimer's pathology, and might be used for early detection of increased risk for dementia development.

Cerebrovascular Reserve Capacity as a Predictor of Postoperative Delirium: A Pilot Study.

Introduction: Postoperative delirium is a common complication after cardiac surgery with cardiopulmonary bypass (CPB). Compromised regulation of the cerebral circulation may be a predisposing factor for delirium. However, the potential relationship between cerebrovascular reserve capacity and delirium is unknown. The aim of this study was to investigate if impaired cerebrovascular reserve capacity was associated with postoperative delirium. Methods: Forty-two patients scheduled for cardiac surgery with CPB were recruited consecutively. All patients underwent preoperative transcranial Doppler (TCD) ultrasound with calculation of breath-hold index (BHI). BHI < 0.69 indicated impaired cerebrovascular reserve capacity. In addition, patients were examined with preoperative neuropsychological tests such as MMSE (Mini Mental State Examination) and AQT (A Quick Test of cognitive speed). Postoperative delirium was assessed using Nursing Delirium Screening Scale (Nu-DESC) in which a score of ≥2 was considered as delirium. Results: Six patients (14%) scored high for postoperative delirium and all demonstrated impaired preoperative cerebrovascular reserve capacity. Median (25th-75th percentile) BHI in patients with postoperative delirium was significantly lower compared to the non-delirium group [0.26 (-0.08-0.44) vs. 0.83 (0.57-1.08), p = 0.002]. Preoperative MMSE score was lower in patients who developed postoperative delirium (median, 25th-75th percentile; 26.5, 24-28 vs. 28.5, 27-29, p = 0.024). Similarly, patients with postoperative delirium also displayed a slower performance during the preoperative cognitive speed test AQT color and form (mean ± SD; 85.8 s ± 19.3 vs. 69.6 s ± 15.8, p = 0.043). Conclusion: The present findings suggest that an extended preoperative ultrasound protocol with TCD evaluation of cerebrovascular reserve capacity and neuropsychological tests may be valuable in identifying patients with increased risk of developing delirium after cardiac surgery.

Assessment of Upper Extremity Venous Compliance in Patients With Abdominal Aortic Aneurysms.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is associated with morphological and functional changes in both aneurysmal and non-aneurysmal arteries. However, it remains uncertain whether similar changes also exist in the venous vasculature. The aim of this study was to evaluate global venous function in patients with AAA and controls. METHODS: This experimental study comprised 31 men with AAA (mean ± standard deviation age 70.0 ± 2.8 years) and 29 male controls (aged 70.6 ± 3.4 years). Venous occlusion plethysmography (VOP) was used to evaluate arm venous compliance at venous pressures between 10 and 60 mmHg in steps of 5 mmHg. Compensatory mobilisation of venous capacitance blood (capacitance response) was measured with a volumetric technique during experimental hypovolaemia induced by lower body negative pressure (LBNP). RESULTS: The VOP induced pressure-volume curve was significantly less steep in patients with AAA (interaction, p < .001), indicating lower venous compliance. Accordingly, the corresponding pressure-compliance curves displayed reduced venous compliance at lower venous pressures in patients with AAA vs. controls (interaction, p < .001; AAA vs. control, p = .018). After adjusting for arterial hypertension, diabetes mellitus, hyperlipidaemia, chronic obstructive pulmonary disease, and smoking, VOP detected differences in venous compliance remained significant at low venous pressures, that is, at 10 mmHg (p = .008), 15 mmHg (p = .013), and 20 mmHg (p = .026). Mean venous compliance was negatively correlated with aortic diameter (r = -.332, p = .010). Mobilisation of venous capacitance response during LBNP was reduced by approximately 25% in patients with AAA (p = .030), and the redistribution of venous blood during LBNP was negatively correlated with aortic diameter (r = -.417, p = .007). CONCLUSION: Men with AAA demonstrated reduced venous compliance and, as a result, a lesser capacity to mobilise peripheral venous blood to the central circulation during hypovolaemic stress. These findings imply that the AAA disease may be accompanied by functional changes in the venous vascular wall.

Impact on venous haemodynamics after treatment of great saphenous vein incompetence using plethysmography and duplex ultrasound.

OBJECTIVES: To evaluate postoperative venous haemodynamics and quality of life after treatment of great saphenous vein (GSV) incompetence. METHODS: Radiofrequency ablation and high ligation and stripping were performed in 62 patients (65 limbs) and 58 (65 limbs), respectively. Phlebectomies were performed in both modalities. Strain-gauge plethysmography on the foot combined with superficial venous occlusion was used to measure refilling time after knee bends. Strain-gauge plethysmography, duplex ultrasound and quality of life were assessed before and one month after treatment. RESULTS: Duplex ultrasound displayed successful intervention in all but two limbs. Refilling time increased similar in radiofrequency ablation and high ligation and stripping after treatment (p < 0.001). Postoperatively, strain-gauge plethysmography detected remaining reflux in 71% of the patients. Multivariate analysis showed that two or more incompetent calf branches were associated with remaining reflux (OR 4.82 (95% CI: 1.33-17.5), p = 0.02). No difference in quality of life was seen in patients with remaining reflux. CONCLUSIONS: Despite successful treatment, a majority of the limbs showed remaining reflux, in which incompetent calf branches appear to play an important role.Clinicaltials.gov: Lower Limb Venous Insufficiency and the Effect of Radiofrequency Treatment Versus Open Surgery. Nr: NCT02397226.

Cardiovascular biomarkers and echocardiographic findings at rest and during graded hypovolemic stress in women with recurrent vasovagal syncope.

INTRODUCTION: Vasovagal reflex is the most common type of syncope but its etiology is not fully elucidated. Venous return and cardiac output are key in hemodynamic control. The aim of the study was to assess cardiovascular biomarkers and echocardiographic measures at rest and during hypovolemia in women with and without a history of vasovagal syncope. METHODS: Fourteen women (aged 18-30) suffering from recurrent vasovagal syncope and 15 age-matched healthy women were included. Graded lower body negative pressure (LBNP) was used to create central hypovolemic stress until signs of presyncope occurred. Echocardiography was applied at rest and throughout LBNP. Cardiovascular biomarkers: copeptin, mid-regional proadrenomedullin, mid-regional pro-ANP, C-terminal proendothelin-1, and plasma norepinephrine were measured both at rest and throughout graded hypovolemia to presyncope. RESULTS: Women prone to vasovagal syncope presented with a narrower right ventricle (RV) (29 ± 1 vs 32 ± 1 mm, P < .05), smaller left atrium (36 ± 2 vs 47 ± 3 cm3 , P < .01) and lower cardiac output at rest (3.1 ± 0.2 vs 3.7 ± 0.2 L/min, P < .05) and during graded hypovolemia (P < .05). Copeptin was elevated at rest (4.3 ± 0.8 vs 2.5 ± 0.2 pmol/L, P < .05) and increased more in women with vasovagal syncope during progression of LBNP (P < .01). At rest, lower C-terminal proendothelin-1 (35 ± 5 vs 46 ± 2 pmol/L, P < .05) and higher norepinephrine levels (1.1 ± 0.1 vs 0.8 ± 0.1 nmol/L, P < .01) were seen in women with vasovagal syncope. CONCLUSION: Women prone to vasovagal syncope demonstrate reduced cardiac preload, lower cardiac output, as well as increased release of vasopressin in rest and during hypovolemic challenge. The results emphasize the importance of venous return and cardiac output in the pathogenesis of vasovagal syncope.

Reduced compensatory responses to maintain central blood volume during hypovolemic stress in women with vasovagal syncope.

Although vasovagal syncope (VVS) is a common clinical condition, the underlying pathophysiology is not fully understood. A decrease in cardiac output has recently been suggested as a factor in orthostatic VVS. The aim was to investigate compensatory mechanisms to maintain central blood volume and venous return during hypovolemic stress in women with VVS. Fourteen VVS women (25.7 ± 5.0 yr) and 15 matched controls (22.8 ± 3.2 yr) were investigated. Single-step and graded lower body negative pressure (LBNP) to presyncope were used to create hypovolemic stress. Peripheral mobilization of venous blood from the arm (capacitance response and net capillary fluid absorption) and lower limb blood pooling (calf capacitance response) were evaluated using a volumetric technique. Cardiovascular responses and plasma norepinephrine (P-NE) were measured. Resting P-NE was elevated in VVS women (P < 0.01). Despite a similar hypovolemic stimulus, the increase in P-NE was blunted (P < 0.01) and the maximal percent increase in total peripheral resistance was reduced (P < 0.05) during graded LBNP in VVS women. The arm capacitance response was slower (P < 0.05) and reduced in VVS women at higher levels of LBNP (P < 0.05). Capillary fluid absorption from extra- to intravascular space was reduced by ∼40% in VVS women (P < 0.05). Accordingly, the reduction in cardiac output was more pronounced (P < 0.05). In conclusion, in VVS women, mobilization of peripheral venous blood and net fluid absorption from tissue to blood during hypovolemic stress were decreased partly as a result of an attenuated vasoconstrictor response. This may seriously impede maintenance of cardiac output during hypovolemic stress and could contribute to the pathogenesis of VVS.

Reduced venous compliance: an important determinant for orthostatic intolerance in women with vasovagal syncope.

The influence of lower limb venous compliance on orthostatic vasovagal syncope (VVS) is uncertain. The most widespread technique to calculate venous compliance uses a nonphysiological quadratic regression equation. Our aim was therefore to construct a physiologically derived venous wall model (VWM) for calculation of calf venous compliance and to determine the effect of venous compliance on tolerance to maximal lower body negative pressure (LBNP). Venous occlusion plethysmography was used to study calf volume changes in 15 women with VVS (25.5 ± 1.3 yr of age) and 15 controls (22.8 ± 0.8 yr of age). The fit of the VWM and the regression equation to the experimentally induced pressure-volume curve was examined. Venous compliance was calculated as the derivative of the modeled pressure-volume relationship. Graded LBNP to presyncope was used to determine the LBNP tolerance index (LTI). The VWM displayed a better fit to the experimentally induced pressure-volume curve (P < 0.0001). Calf blood pooling was similar in the groups and was not correlated to the LTI (r = 0.204, P = 0.30). Venous compliance was significantly reduced at low venous pressures in women with VVS (P = 0.042) and correlated to the LTI (r = 0.459, P = 0.014) in the low pressure range. No correlation was found between venous compliance at high venous pressures and the LTI. In conclusion, the new VWM accurately adopted the curvilinear pressure-volume curve, providing a valid characterization of venous compliance. Reduced venous compliance at low venous pressures may adversely affect mobilization of peripheral venous blood to the central circulation during hypovolemic circulatory stress in women with VVS.

Thirst response to acute hypovolaemia in healthy women and women prone to vasovagal syncope.

The present study measured self-perceived thirst and plasma angiotensin II (ATII) concentrations during graded hypovolaemic stress, induced by lower body negative pressure (LBNP), to elucidate the dependence of thirst on haemodynamics. A total of 24 women aged between 20 and 36 (mean age, 23) years rated their thirst on a visual analogue scale, graded from 0 to 100, when LBNP of 20, 30 and 40 mmHg was applied. Half of the women had a history of vasovagal syncope (VVS). The results showed that the thirst score increased three-fold when LBNP was applied, from 11 (median; 25th-75th percentiles, 9-25) to 34 (27-53; P<0.001). The women in the VVS group had twice as great an increase as those without a history of VVS (P<0.02). The plasma ATII concentration increased significantly in response to LBNP, both in the VVS group and in the control group, but the changes did not correlate with thirst. Application of LBNP decreased systolic and mean arterial pressures, cardiac output and pulse pressure (P<0.001 for all), but thirst correlated only with increase in heart rate and, independently, with reduction of mean arterial pressure. In conclusion, thirst and ATII increase in response to hypovolaemic stress, but are not statistically related. The haemodynamic parameter that was most strongly related to thirst was tachycardia.