Summaries of recent phlebological abstracts

J Vasc Surg: Venous and Lym Dis 2019; 7: 428–440.

The study examined the correlations between air plethysmography (APG) and ambulatory venous pressure (AMVP) parameters and the role of “calf pump failure” in chronic venous disease (CVD). A total of 8456 limbs in 4610 patients investigated for CVD during a 20-year period were analyzed. APG and AMVP data were available in 4599 limbs for calculation of Pearson correlation coefficient; 1347 of these limbs had significant iliac vein stenosis, proven by intravascular ultrasound. Venn diagrams were used to explore overlapping incidence of APG and AMVP abnormalities. APG calf volume and reflux (venous volume, venous filling index) showed progressively significant deterioration with advancing CEAP clinical class, anatomic extent of reflux (superficial, deep, perforator), and reflux severity (axial reflux, segmental score). Notably, calf ejection volume increased in a nearly linear fashion (R = 0.71) to venous volume such that residual volume fraction (RVF) remained normal even in the worst of these categories. AMVP too progressively deteriorated with clinical disease and reflux severity. Venous filling time was the key parameter as the pressure drop alone was abnormal in only 4% of the limbs analyzed. There was no correlation between RVF and AMVP (R = 0.22) or between AMVP and many other APG parameters. Venn distribution showed only minor overlap (30%) between AMVP and key APG abnormalities overall, but the overlap increases from 40% to 70% in advanced clinical and reflux categories. AMVP was rarely abnormal (7%) when APG was normal. Median AMVP was normal in calf pump failure categories, however defined (subnormal ejection fraction, RVF, or both). Median AMVP is normal in venous obstruction without reflux, while AMVP abnormalities are associated three to seven times more with reflux than with obstruction. The authors concluded that APG (venous filling index) is a useful index of reflux. Calf pump ejection is a powerful and plastic compensatory mechanism, and calf pump failure is rare. Ambulatory venous hypertension is dominantly associated with reflux and less with obstruction. AMVP too worsens with clinical and reflux severity categories. However, there is little correlation between APG and AMVP parameters as APG measures volume and AMVP measures pressure, each in its own domain, and the volume–pressure curve is nonlinear. AMVP may be omitted in routine clinical testing if APG is normal, as the yield (7%) will be very low. AMVP reflects venous hypertension, the end stage in CVD. AMVP should be used to identify such cases when APG is abnormal.

J Vasc Surg Venous Lymphat Disord 2019 May 5. doi: 10.1016/j.jvsv.2019.01.060. [Epub ahead of print].

The authors in this Portuguese 13-year intrahospital database study ascertained whether there was a difference in outcomes between varicose vein (VV) surgery performed by surgeons with and without formal vascular training. Three hundred and fifteen random patients submitted to saphenous high ligation and stripping (175 patients from six vascular surgery departments and 140 patients from five general surgery divisions) were further queried over the phone, whereby additional nonregistered outcomes were evaluated: preoperative venous ultrasound, impact on quality of life by the 14-item Chronic Venous Insufficiency Quality of Life Questionnaire, visual analogue scale evaluation (score of 1 to 5) of the aesthetic results and general satisfaction, work absence days, and time to return to physical activities. There were a total of 153,382 patients submitted to VV surgery. Forty-nine percent were operated on by general surgeons and 40% by vascular surgeons; in 11%, it was not possible to identify the specialty performing the operation. Twenty-three deaths were registered (no differences between groups). In the general surgery cohort, 14% of patients were hospitalized for more than one night compared with 3% in the vascular group (P < .001). Reintervention rate was significantly higher in the general surgery group (13.5% vs. 8.2%; P < .001). Rate of outpatient surgery was higher in the vascular surgery group (60% vs. 36%; P < .001). Satisfaction and improvement in quality of life were equal in both groups (4.2 vs. 4.0 (P = .275) and 35% vs. 36% (P = .745), respectively). Patients operated on by general surgeons reported worse surgical scars (2.8 vs. 2.1; P = .007), higher number of residual VVs (2.4 vs. 1.7; P = .006), higher number of days absent from work (40 vs. 27 days; P = .005), and took longer to resume physical activities (60 vs. 41 days; P = .001).

The authors concluded that despite the majority of VV surgery in Portugal is executed by general surgeons, this study highlights important advantages when VV surgery is performed by vascular-trained surgeons.

Einstein (Sao Paulo) 2019 May 2; 17(2): eAO4526. doi: 10.31744/einstein_journal/2019AO4526.

In this 49-patient study, the authors compared the use of the radiofrequency ablation to high tie and saphenectomy from the saphenofemoral junction to the ankle. C (CEAP) classes 2 to 4 for clinical signs, etiology, anatomic distribution, and pathophysiology were assessed at baseline, four weeks, and one year. Patients were reexamined at one year and three years for varicose vein reoccurrence. The success rate per limb (p = 0.540), VCSS (p = 0.636), AVVQ (p = 0.163), and clinical complications were similar in the two treatment groups. Nevertheless, the radiofrequency ablation cohort had a significantly shorter length of hospital stay (0.69 ± 0.47) and absence from activities (8.62 ± 4.53), p < 000.1.

The authors concluded that patients submitted to radiofrequency ablation had an equal occlusion rate, clinical recurrence, and improvement in quality of life; however, these patients spent less time hospitalized and away from their daily activities during recovery.

Expert Rev Cardiovasc Ther 2019 May 17. doi: 10.1080/14779072.2019. [Epub ahead of print]

This article aims to compare medication adherence and persistence between warfarin and direct oral anticoagulants (DOACs) and identify reported adherence barriers. As with other chronic illness, medication non-adherence continues to be a problem, and appropriate adherence to long-term anticoagulation therapy is needed to improve patient health outcomes and to reduce health expenditure associated with hospitalizations and emergency visits. Areas covered: Warfarin and DOACs such as apixaban, rivaroxaban, edoxaban, and dabigatran have demonstrated effectiveness in the management of atrial fibrillation, deep vein thrombosis and pulmonary embolism. Adherence and long-term persistence to oral anticoagulants is highly associated with reduced adverse events. A systematic literature search from 2013 to 2018 examined the primary outcome of adherence and persistence. Expert commentary: Currently, warfarin is less preferred over DOACs due to associated complications like narrow therapeutic window, inconvenience, and increased risk of adverse events. At the same time, the lack of monitoring with DOACs in combination with cost issues may negatively impact medication adherence. Examining adherence barriers identified in the literature is the first step to designing effective interventions aimed at enhancing adherence in this high-risk population.

Am J Cardiol. 2019 Apr 23. pii: S0002-9149(19)30463-1. doi: 10.1016/j.amjcard.2019.04.024. [Epub ahead of print]

Mortality according to the use inferior vena cava (IVC) filters in patients with pulmonary embolism (PE) and heart failure (HF) has been sparsely studied. In the present investigation, we assess whether IVC filters in stable patients with PE and HF reduce mortality. This is a retrospective cohort study of administrative data from the Premier Healthcare Database, 2009 through 2015. Patients aged ≥18 years hospitalized with a primary diagnosis of PE and a discharge diagnosis of HF were identified by International Classification of Diseases-Ninth Revision-Clinical Modification codes. Exclusions were unstable patients (in shock or on a ventilator), patients who underwent pulmonary embolectomy, and patients with co-morbidities. In-hospital all-cause mortality was 102 of 2423 (4.2%) with an IVC filter compared with 686 of 14,063 (4.9%) without an IVC filter (p = 0.16). Only patients aged >80 years showed a lower in-hospital all-cause mortality with IVC filters, 38 of 933 (4.1%) with an IVC filter compared with 307 of 4,486 (6.8%) without an IVC filter (p = 0.0012). In conclusion, stable patients with PE and HF, if aged >80 years, showed a reduced in-hospital all-cause mortality with IVC filters.

Vasa 2019: Apr 24: 1–8. doi: 10.1024/0301-1526/a000792. [Epub ahead of print].

The authors compared outcomes in this 400-patient prospective comparative study of cyanoacrylate glue versus endovenous laser ablation for the management of incompetent great saphenous veins. The study period was from April 2014 through April 2016. There were 208 procedures in the cyanoacrylate ablation group (CAA) and 204 in the endovenous laser ablation group (EVLA). Operative time was 13 ± 3.4 min in the CAA and 31.7 ± 8.8 min in the EVLA (p < 0.001). All procedures in both groups were successful, and the target vein segments were fully occluded at the end of the procedure. Periprocedural pain was less in the CAA (p < 0.001). Induration, ecchymosis, and paresthesia rates were significantly higher in the EVLA (p < 0.001). The mean length of follow-up was 14 months (range 10–16). The 3-, 6-, and 12-month closure rates were 97.4%, 95.6%, and 94.1% for EVLA and 98.6%, 97.1%, and 96.6% for CAA, respectively. In both groups, there was no statistical significant difference among the Venous Clinical Severity Score and Chronic Venous Insufficiency Quality of Life Questionnaire.

The authors concluded that the management of incompetent great saphenous veins with endovenous cyanoacrylate ablation and laser ablation both result in high occlusion rates. Endovenous cyanoacrylate ablation technique is faster and does not require tumescent anesthesia.

PLoS Genet 2019; 2019 Apr 18; 15(4): e1008110. doi: 10.1371/journal.pgen.1008110. eCollection 2019 Apr.

The authors studied genetics in 408,455 European-ancestry individuals with varicose veins (VVs). They identified the 12 reliably associated loci that explain 13% of the single nucleotide polymorphisms (SNP) based heritability and prioritized the most likely causal genes CASZ1, PIEZO1, PPP3R1, EBF1, STIM2, HFE, GATA2, NFATC2, and SOX9. VVs-associated variants within these loci exhibited pleiotropic effects on several phenotypes including blood pressure/hypertension and blood cell traits. Gene set enrichment analysis revealed gene categories related to abnormal vasculogenesis. Genetic correlation analysis confirmed known epidemiological associations between VVs and deep venous thrombosis, weight, rough labor, and standing job, and found a genetic overlap with multiple traits that have not been previously suspected to share common genetic background with VVs. These traits included educational attainment, fluid intelligence, and prospective memory scores, walking pace (negative correlation with VVs), smoking, height, number of operations, pain, and gonarthrosis (positive correlation with VVs). Finally, Mendelian randomization analysis provided evidence for causal effects of plasma levels of MICB and CD209 proteins, and anthropometric traits such as waist and hip circumference, height, weight, and both fat and fat-free mass.

The authors concluded that the results provide insight into both VVs genetics and etiology. In addition, the revealed genes and proteins can be considered as good candidates for follow-up functional studies and might be of interest as potential drug targets.

Eur J Med Chem 2019; 176: 68–91.

Venous insufficiency is most often caused by the damage to the valves and walls of the veins. The mechanism of varicose vein formation is complex. It is, however, based on hypotensive blood vessels, hypoxia, and other mechanisms associated with inflammation. This work describes mechanisms related to the formation and development of the varicose vein. It discusses risk factors, pathogenesis of chronic venous disease, markers of the epithelial and leukocyte activation, state of hypoxia and inflammation, reactive oxygen species (ROS) generation, and oxidative stress. Additionally, this paper describes substances of plant origin used in the treatment of venous insufficiency. It also considers the structure of the molecules, their properties, and their mechanisms of action, the structure–activity relationship and chemical properties of flavonoids and other substances. The flavonoids include quercetin derivatives, micronized purified flavonoid fraction (Daflon), natural pine bark extract (Pycnogenol), and others such as triterpene saponine, extracts from Ruscus aculeatus and Centella asiatica, Ginkgo biloba extract, coumarin dereivatives that are used in chronic venous insufficiency. Flavonoids are natural substances found in plants, including fruits, vegetables, flowers, and others. They are important to the circulatory system and critical to blood vessels and the blood flow. Additionally, they have antioxidant, anti-inflammatory properties.