Valve Incompetence Research Articles

Tissue Level Mechanical Properties and Extracellular Matrix Investigation of the Bovine Jugular Venous Valve Tissue.

Jugular venous valve incompetence has no long-term remedy and symptoms of transient global amnesia and/or intracranial hypertension continue to discomfort patients. During this study, we interrogate the synergy of the collagen and elastin microstructure that compose the bi-layer extracellular matrix (ECM) of the jugular venous valve. In this study, we investigate the jugular venous valve and relate it to tissue-level mechanical properties, fibril orientation and fibril composition to improve fundamental knowledge of the jugular venous valves toward the development of bioprosthetic venous valve replacements. Steps include: (1) multi loading biaxial mechanical tests; (2) isolation of the elastin microstructure; (3) imaging of the elastin microstructure; and (4) imaging of the collagen microstructure, including an experimental analysis of crimp. Results from this study show that, during a 3:1 loading ratio (circumferential direction: 900 mN and radial direction: 300 mN), elastin may have the ability to contribute to the circumferential mechanical properties at low strains, for example, shifting the inflection point toward lower strains in comparison to other loading ratios. After isolating the elastin microstructure, light microscopy revealed that the overall elastin orients in the radial direction while forming a crosslinked mesh. Collagen fibers were found undulated, aligning in parallel with neighboring fibers and orienting in the circumferential direction with an interquartile range of −10.38° to 7.58° from the circumferential axis (n = 20). Collagen crimp wavelength and amplitude was found to be 38.46 ± 8.06 µm and 4.51 ± 1.65 µm, respectively (n = 87). Analyzing collagen crimp shows that crimp permits about 12% true strain circumferentially, while straightening of the overall fibers accounts for more. To the best of the authors’ knowledge, this is the first study of the jugular venous valve linking the composition and orientation of the ECM to its mechanical properties and this study will aid in forming a structure-based constitutive model.

Impact of Leadless Pacemaker Therapy on Cardiac and Atrioventricular Valve Function Through 12 Months of Follow-Up.

Endocardial pacemaker leads and right ventricular (RV) pacing are well-known causes of tricuspid valve, mitral valve, and cardiac dysfunction. Lead-related adverse consequences can potentially be mitigated by leadless pacemaker (LP) therapy by eliminating the presence of a transvalvular lead. This study assessed the impact of LP placement on cardiac and valvular structure and function. Echocardiographic studies before and 12±1 months after LP implantation were performed between January 2013 and May 2018 at our center and compared with age- and sex-matched controls of dual-chamber transvenous pacemaker recipients. A total of 53 patients receiving an LP were included, of whom 28 were implanted with a Nanostim and 25 with a Micra LP device. Tricuspid valve regurgitation was graded as being more severe in 23 (43%) patients at 12±1 months compared with baseline ( P<0.001). Compared with an apical position, an RV septal position of the LP was associated with increased tricuspid valve incompetence (odds ratio, 5.20; P=0.03). An increase in mitral valve regurgitation was observed in 38% of patients ( P=0.006). LP implantation resulted in a reduction of RV function, according to a lower tricuspid annular plane systolic excursion ( P=0.003) and RV tricuspid lateral annular systolic velocity ( P=0.02), and a higher RV Tei index ( P=0.04). LP implantation was further associated with a reduction of left ventricular ejection fraction ( P=0.03) and elevated left ventricular Tei index ( P=0.003). The changes in tricuspid valve regurgitation in the LP group were similar to the changes in the dual-chamber transvenous pacemaker control group (43% versus 38%, respectively; P=0.39). LP therapy is associated with an increase in tricuspid valve dysfunction through 12 months of follow-up; yet it was comparable to dual-chamber transvenous pacemaker systems. Furthermore, LP therapy seems to adversely impact mitral valve and biventricular function.

Updates in Aortic Valve Sparing Surgery

For more than 90 years ago Aortic valve-sparing operations had been performed, but only recently surgeons have been able to match the aortic root disorder to the operative procedure correctly The development of aortic valve-sparing operations (re-implantation of the aortic valve and remodeling of the aortic root) expanded the surgical issues for treating patients with aortic root dilation caused by a variety of disorders. Young adults with aortic root aneurysms associated with genetic syndromes are ideal candidates for re-implantation of the aortic valve, and the long-term results have been excellent. Incompetent bicuspid aortic valves with dilated aortic annuli are also satisfactorily treated with the same type of operation. Older patients with ascending aortic aneurysm and aortic insufficiency secondary to dilated sino-tubular junction and a normal aortic annulus can be treated with remodeling of the aortic root or with re-implantation of the aortic valve. Annular dilation is often present in patients with incompetent BAV, correction of annular dilation is important, and re-implantation of the aortic valve may be the best option. There is a variety of techniques for Cusp Repair, considered as one of the valve-sparing techniques. Aortic valve-sparing surgery is performed to prevent hazards of Prosthetic valve implantation which is the most widely used therapeutic option for aortic regurgitation (AR), but complications associated with prosthetic valves, with an incidence of 3–5% patient/year, and the need for anticoagulation in mechanical valves, force us to consider aortic valve repair as an alternative to the prosthetic implant, especially in young people with many potential years of life for these complications. Aim of the work: This paper aims to have a description of surgical and dynamic anatomy of the aortic root, pathological changes that may affect it and important investigation for proper diagnosis and surgical planning. Highlights for aortic valve-sparing operations and their modification Review of Literature: Aortic valve-sparing (AVS) operations have become established alternatives to composite valve graft (CVG) procedures for patients with aortic root aneurysms and favorable aortic cusp morphology. The theoretical benefits of AVS procedures include avoiding the complications associated with prosthetic valves, specifically the risks of systemic thromboembolism and lifelong anticoagulation associated with mechanical valves. Summary: The development of aortic valve-sparing operations (re-implantation of the aortic valve and remodeling of the aortic root) expanded the surgical issues for treating patients with aortic root dilation caused by a variety of disorders.

Cardiac MRI clinches diagnosis of Libman-Sacks endocarditis

A 28-year-old man presented to our hospital with exertional dyspnoea that had become gradually worse over the previous 3 months. On clinical examination of his heart, the apex was displaced laterally and inferiorly, the first heart sound was muffled, and there was a grade IV–VI apical pan-systolic murmur. 2 days after admission, the patient developed a non-haemorrhagic stroke. A transthoracic echocardiogram showed a dilated left ventricle with global hypokinesia and impaired systolic function: the left ventricular ejection fraction was 33% (video 1). A roughly spherical, relatively immobile mass, approximately 1·6 cm × 1·6 cm, was seen attached to the base of the posterior leaflet of the mitral valve (video 2). There was severe, eccentric, posteriorly directed mitral valve incompetence (video 1). A transoesophageal echocardiogram confirmed the transthoracic echocardiogram findings, but it did not help us understand the true nature of the mass (video 3). A three-dimensional transoesophageal echocardiogram confirmed the previous findings (appendix and video 3). All blood cultures obtained were negative. Additionally, we did a cardiac MRI to investigate the nature of the tissue or tissues of the abnormality. After confirming the location of the mass (video 3), the MRI showed an increased T2-weighted signal (figure) with an isointense T1-weighted signal. It also had an increased signal on delayed hyperenhancement (figure), with patchy myocardial fibrosis indicating myocarditis. Taken together, all these findings confirmed that the mass was not a thrombus or the vegetation of an infective endocarditis. We concluded the diagnosis was most likely to be non-infective endocarditis—commonly known as Libman-Sacks endocarditis. Laboratory investigations supported this diagnosis: a lupus anticoagulant test was positive and the levels of anticardiolipin IgM and anti-β2 glycoprotein I IgG antibodies—markers of the antiphospholipid syndrome—were increased. We started treatment with prednisone, an immunosuppressant (mycophenolate mofetil), anticoagulation, and measures to prevent cardiac failure. Pleasingly, the patient's clinical condition improved remarkably, and his left ventricular function increased with an ejection fraction of 43%; the mitral valve mass also reduced in size to 0·5 cm × 0·4 cm (figure and video 4).

Aortic Insufficiency during LVAD Support: A Mock Loop Study

Purpose Aortic valve (AoV) insufficiency (AI) is a serious complication in more than 20% of Left Ventricle Assist Device (LVAD) patients within 12 months of LVAD implantation. Normal AoV have developed AI following long-term LVAD support,which has been associated with a significant reduction in LVAD patient survival. During LVAD support, the AoV pressure difference is increased, which reduces systolic opening and worsens regurgitant flow through an incompetent valve. The goal of this study was to measure the effect of LVAD support on intraventricular flow during AI. Methods The velocity field was measured in the midplane of a dilated silicone LV model attached to a rotary LVAD (Abbott Labs, Chicago IL) in a mock circulatory loop. A Pre-LVAD without AI condition (BL) of 20% ejection fraction was established, followed by testing at three LVAD speeds. AI was created with a small 3-D printed stent which was nonobstructive to forward flow but prevented the leaflets from fully closing. LV and aortic pressure, and LVAD and distal aortic flow, were recorded. Results At the Pre-LVAD BL condition, the mean aortic pressure was 63 mmHg and the cardiac output was 2.3 L/min; AI maintained a similar pressure but reduced flow to 1.8 L/min producing a 32% regurgitant fraction (mild-moderate AI). At an LVAD speed of 6400rpm, total systemic flow was 4.3 L/min and 3.1 L/min for BL and AI, respectively, and LVAD flow was 4.2 and 3.6 L/min, producing a 45% regurgitant fraction (moderate-severe AI). The reduction of systemic flow was accompanied by higher LVAD flow, confirming that a regurgitant loop was present. Net forward flow through AoV during BL decreased progressively by 23%, 12% and 0.5% for 4800, 5400, and 6400rpm respectively. AI reduced forward flow and increased backward flow, such that net forward flow was 0.5%, -14%, and -17% at 4800, 5400 and 6400rpm. The AI vena contracta width increased from 2.3 to 3.4 mm as LVAD speed increased. Conclusion Overall, the results showed that an initially mild level of AI worsened with LVAD support prior to any remodeling, simply due to the altered biomechanics of the AoV. These findings provide a foundation for new strategies that can restore AoV biomechanics and reduce the impact of AI on patients with LVAD support.

The influence of May-Thurner syndrome on post-thrombotic syndrome in young women.

Background: The mechanism for post-thrombotic syndrome (PTS), the most important long-term sequelae of deep venous thrombosis, is not entirely known. It is probably caused by venous hypertension due to venous insufficiency and venous obstruction. Venous hypertension could also be a consequence of the May-Thurner syndrome (MTS), i.e. the obstruction of the common iliac vein. The aim of the present study was to explore if women with untreated MTS and a history of proximal DVT develop PTS more frequently. Patients and methods: A cohort of 68 female patients with a history of proximal left-sided DVT in the past were evaluated. According to Villalta score, they were segregated in two groups- with and without PTS (Villalta score≥5 or<5points, respectively). For the diagnosis of MTS, magnetic resonance venography was performed. Results: Out of 68 patients, 25 developed PTS (36.8%). Recurrent DVT, older age, pre-existent chronic venous insufficiency, and shorter compression stockings wearing time were statistically related to PTS. Deep and superficial valve incompetence was also significantly related to PTS, while incomplete thrombus removal showed only a trend towards PTS development. On the other hand, MTS per se turned out not to be linked to PTS. Conclusions: Our study suggests that women with MTS might not develop PTS more often, which puts aggressive treatment of MTS under question. More clinical trials are warranted to further examine this yet not fully explained field.

Imaging Appearance and Nonsurgical Management of Pelvic Venous Congestion Syndrome.

Pelvic venous congestion syndrome (PVCS) is a challenging and complex cause of chronic pelvic pain in female patients. PVCS due to incompetent vein valves is the combination of gonadal vein reflux and pelvic venous engorgement in patients with chronic pelvic pain without other causes. However, pelvic venous engorgement and gonadal vein reflux can be seen in patients without pelvic pain, which makes obtaining a detailed history and physical examination important for workup and diagnosis. The underlying cause of PVCS may be incompetent gonadal vein valves or structural causes such as left renal vein compression with an incompetent gonadal vein valve (nutcracker syndrome) or iliac vein compression (May-Thurner configuration) with reflux into the ipsilateral internal iliac vein. Venography is considered the criterion standard for imaging diagnosis; however, more recently, US and MRI have been shown to provide adequate accuracy for diagnosis. Noninvasive imaging studies aid in the diagnosis of PVCS and also aid in pretreatment planning. When PVCS is caused by incompetent gonadal vein valves, treatment typically is performed by means of embolization via a minimally invasive catheter with excellent technical and clinical success rates. When PVCS is caused by venous obstruction, the obstruction must be treated first before gonadal vein embolization and sclerotherapy are considered. ©RSNA, 2019 Online supplemental material is available for this article.

Evaluation of Results and Patients’ Satisfaction of Alar Base Resection Surgery after Rhinoplasty Operations in 15 Khordad Hospital

Background: Alar base surgery is one of the controversial issues in rhinoplasty. In this surgery the nasal base width and alar flaring is got smaller with some kind of procedures. One of these procedures is wedge resection of alar base. This procedure may accompany with either some dissatisfaction of scars and adverse effects or complications. In this study, we evaluate the patient satisfaction of scar and possible complications. Materials and Methods: A total of 120 rhinoplasty patients at 15 khordad hospital were candidates for alar base wedge resection due to broad nasal base and / or alar flaring who were chosen for this study. We recorded and examined these patients before and minimum 6 months after surgery, then evaluated these information and data, which finally, compared all the preoperation and postoperation findings. Results: Mean age of patients was 30.11 years old. The full satisfaction of scar was 85.5% (103), but 6.7% (8) of patients had not satisfaction of scar due to visible scar in their alar facial groove. The rate of nostril symmetry satisfaction was 79.2% (95) and 8.3% (10) was dissatisfied due to nostril asymmetry. There was no external valve incompetency nor alar and sill notching in our study. There was not any narrowing of nostrils as well. The mean interalar distance preoperatively was 35.88 mm, which reduced to 32.61mm of mean diameter after surgery, (P-value = 0.000). Alar flaring correction was 88% (106) which was an acceptable consequence. Conclusion: The results of present study showed that in spite of surgeons fear for scar and some common complications after alar base resection, the satisfaction rate of our patients in this study were high, and complications frequencies were low. Therefore, we advise that it is better and wiser to do this operation in indicated patients surely within primary rhinoplasty and do not postpone it to another surgery.

Almost All Incompetent BAV Should Be Repaired

The short answer to this topic is "No, most incompetent bicuspid aortic valve should not be repaired." Aortic valve repair certainly plays an important role in the management of incompetent bicuspid aortic valve of young patients, and the selection criteria are like those for incompetent tricuspid aortic valve. The tissue that makes the cusps should normal or have minor abnormalities easily corrected by surgery such as plication of the free margin. In addition, the anatomic orientation of the conjoint and the normal cusps should be approximately at 180°. If the root is dilated, reimplantation of the aortic valve is likely the most reproducible approach, and if the root is not dilated but the annulus is, a subannular annuloplasty and correction of the cusp prolapse is adequate. Most patients with incompetent bicuspid aortic valve have malformed, fibrotic and calcified cusps and replacement with either pulmonary autograft or a mechanical aortic valve in young patients and a bioprosthetic aortic valve are likely to provide better long-term outcomes than aortic valve repair.

Incidence of Internal Jugular Vein Valve Incompetence through High versus Low Approach for IJV Cannulation

Incidence of Internal Jugular Vein Valve Incompetence through High versus Low Approach for IJV Cannulation

Surgical ablation of ventricular tachycardia in patients with repaired tetralogy of Fallot†.

Life expectancy of patients with repaired tetralogy of Fallot is normal until adulthood, when it becomes burdened by major complications such as cardiac arrhythmias and heart failure. Ventricular tachycardia (VT), associated with electrical conduction abnormalities in anatomical isthmuses, is the most common complication and is refractory to medical therapy. The arrhythmogenic sources can be surgically ablated during reoperations for pulmonary valve incompetence. The purpose of our study is to evaluate the safety and effectiveness of surgical radiofrequency ablation during PVR and its long-term impact on the occurrence of cardiac events. A total of 118 patients with repaired tetralogy of Fallot underwent reoperation for pulmonary valve regurgitation in IRCCS-Policlinico San Donato between January 2002 and February 2016. Twenty patients with risk factors for ventricular arrhythmia underwent EP testing and were found positive. The mean QRS duration was 178 ms. Right ventricular dysfunction was present in all the patients, and 20% had associated tricuspid regurgitation. The cohort (N = 20), with positive EP study, underwent pulmonary valve replacement and concomitant intraoperative ventricular surgical radiofrequency ablation, targeting the slow conducting isthmuses identified during preoperative electroanatomical mapping. All patients were reviewed at 1 month, 3 months and 6 months with clinical evaluation, echocardiography, ECG and implantable cardioverter-defibrillator interrogation. At 6 months, a postoperative electrophysiological study was performed in all patients, and a cardioverter defibrillator was implanted as primary preventive measure in patients with residual inducible VT. Pulmonary valve replacement and surgical ventricular radiofrequency ablation were performed in all cases. One patient died while on V-V extracorporeal membrane oxygenation (ECMO) due to respiratory failure. There was no late mortality. Follow-up was complete with a median of 6.5 years. During the postoperative EPS study, inducible VT was found in 15.7% of patients who received an implantable cardioverter-defibrillator, whereas VT could no longer be induced in the remaining patients. No procedure-related complication was observed, and freedom from ventricular arrhythmia was 94% and 89.5% at 1 year and 5 years, respectively. Pulmonary regurgitation and right ventricular dysfunction correlate with VT and SCD, but valve replacement alone does not reduce the risk of ventricular tachyarrhythmias. Intraoperative ventricular ablation during reoperation for pulmonary regurgitation prevents the occurrence of ventricular arrhythmias in the early and medium term. Accordingly, this technique may be proposed as a safe associated procedure in selected patients.

The utility of integrating basic echocardiography in routine respiratory intensive care practice

ObjectiveThe aim of this study was to evaluate the impact of integrating basic echocardiography in routine assessment of patients admitted to the respiratory intensive care unit and to assess its effect on the outcome of those patients.Patients and methodsThis prospective cross-sectional study was performed upon 300 patients admitted to the respiratory intensive care unit between January 2015 and December 2015 at Abbasia Chest Hospital. Baseline bedside scanning of patients on admission by portable echo machine for basic echocardiography was reviewed by an experienced cardiologist in all cases as gold standard. Basic echocardiography was done to assess the pericardium, left and right ventricular size and function, valvular lesions, and inferior vena cava. Limited compression ultrasonography was done to detect lower limb deep venous thrombosis (DVT).ResultsBasic echocardiography showed that 91/300 (30.3%) patients had normal echocardiogram, whereas 209/300 (69.7%) patients had cardiac abnormalities. Basic echocardiography added unsuspected serious conditions to the diagnosis in 33 (11%) patients; five patients with massive pericardial effusion, 22 patients who required inotropics due to dilated cardiomyopathy in 11 patients and ischemic cardiomyopathy in 11 patients, five patients with DVT, and one patient with aortic aneurysm. In addition to this, basic echocardiography confirmed suspected massive pulmonary embolism in seven patients and DVT in 13 patients. Basic echo was able to read the whole finding data as compared to standard echo, with mean sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 93, 97, 97, 98, and 98%, respectively, except for probable incompetent and probable normal tricuspid valve; the standard echo had the upper hand (P<0.0001).ConclusionBasic echocardiography in critically ill patients can readily provide adequate information to get a successful diagnosis and management, especially in life-threatening conditions that can be missed at the primary assessment.

Assessment of The Degree of Ischemic Mitral Valve Incompetence Before and After Percutaneous Coronary Intervention

Assessment of The Degree of Ischemic Mitral Valve Incompetence Before and After Percutaneous Coronary Intervention

Great saphenous vein reflux treatment in patients with femoral valve incompetence, the Excluded Saphenous Vein Technique (ESVT): a pilot study.

To describe and evaluate feasibility and efficacy of a saphenous ablation technique performed in patients with varicose veins (VVs), great saphenous vein (GSV) incompetence, and proximal femoral valve incompetence: the Excluded Saphenous Vein Technique (ESVT). Patients with primary great saphenous and proximal femoral valve incompetence underwent ESVT. This technique is composed of selective crossectomy, GSV ligation next to the thigh incompetent tributary vein, and saphenous vein sclerosing performed from the proximal zone. Demographic, clinical and instrumental data were collected. CEAP classification was used to describe VVs severity. The primary outcome was perioperative complications. Secondary outcomes were 30-days, 6-months and 1-years GSV occlusion rate, and VVs recurrence rate. During a ten months period, 104 patients were analyzed. Among these, 82 patients underwent ESVT (59 female, age 50 ± 21 years), eighty C2 and two C5, according to CEAP classification. The average length of GSV treated was 23 ± 9 cm. No intraoperative complications occurred. A 1-year follow-up analysis revealed no partial or complete saphenous recanalization, deep venous thrombosis, pulmonary embolism. No VVs recurrence was detected during the follow-up period among the entire population. ESVT seems to be a safe and effective treatment for primary saphenous reflux and proximal femoral valve incompetence. Further studies are needed to assess long-term results.

Fluid–structure interactions modeling the venous valve

In this study, a fully coupled fluid–structure interaction computational model for a pulsatile flow in the venous valve was developed. An arbitrary Lagrangian–Eulerian formulation is used in the coupled model, considering two domains, specifically the blood flow and the valve leaflets. The effect of the gap width between the valve leaflets (venous valve incompetence) on the valve reverse flow (reflux) has been investigated.

Evaluation of Peak Reflux Velocities with Vector Flow Imaging and Spectral Doppler Ultrasound in Varicose Veins.

Purpose Spectral Doppler ultrasound (SDUS) is used for quantifying reflux in lower extremity varicose veins. The technique is angle-dependent opposed to the new angle-independent Vector Flow Imaging (VFI) method. The aim of this study was to compare peak reflux velocities obtained with VFI and SDUS in patients with chronic venous disease, i. e., pathological retrograde blood flow caused by incompetent venous valves. Materials and Methods 64 patients with chronic venous disease were scanned with VFI and SDUS in the great or the small saphenous vein, and reflux velocities were compared to three assessment tools for chronic venous disease. A flow rig was used to assess the accuracy and precision of the two methods. Results The mean peak reflux velocities differed significantly (VFI: 47.4 cm/s vs. SDUS: 62.0 cm/s, p<0.001). No difference in absolute precision (p=0.18) nor relative precision (p=0.79) was found. No correlation to disease severity, according to assessment tools, was found for peak reflux velocities obtained with either method. In vitro, VFI was more accurate but equally precise when compared to SDUS. Conclusion Both VFI and SDUS detected the pathologic retrograde flow in varicose veins but measured different reflux velocities with equal precision. VFI may play a role in evaluating venous disease in the future.

Comparison of nasal obstruction symptom evaluation, peak nasal inspiratory flowmeter, and rhinomanometry in patients with nasal deformities

Nasal obstruction is the most common symptom in daily otolaryngology practice that correlates with quality of life. Nasal obstruction etiology is multifactorial and can result from mucosal or structural factors. Subjective and objective evaluation approaches are a significant challenge in its diagnosis. This study aimed to evaluate correlations among the nasal obstruction and symptom evaluation (NOSE) and peak nasal inspiratory flowmeter (PNIF) scores and active anterior rhinomanometry values for nasal obstruction diagnosis in subjects with nasal deformities including crooked nose, saddle nose, nasal valve incompetence, and deviated septum. Furthermore, the correlation of nasal obstruction with sleep-disordered breathing was evaluated. Data in this cross-sectional analytical study in 52 consecutive subjects with nasal deformities and 10 consecutive normal subjects were analyzed with the bootstrapping method. Mean nasal resistance in normal subjects and those with nasal deformities were 0.172 and 0.173 Pa/cm3/s, respectively, on 75 Pa. The NOSE score was not significantly correlated with the PNIF score or the nasal airflow resistance determined by rhinomanometry. However, there was a significant correlation between PNIF and nasal airflow resistance.

Benefits of combining change-point analysis with disproportionality analysis in pharmacovigilance signal detection.

Change-point analysis (CPA) is a powerful method to analyse pharmacovigilance data but it has never been used on the disproportionality metric. To optimize signal detection investigating the interest of time-series analysis in pharmacovigilance and the benefits of combining CPA with the proportional reporting ratio (PRR). We investigated the couple benfluorex and aortic valve incompetence (AVI) using the French National Pharmacovigilance and EudraVigilance databases: CPA was applied on monthly counts of reports and the lower bound of monthly computed PRR (PRR-). We stated a CPA hypothesis that the substance-event combination is more likely to be a signal when the 2 following criteria are fulfilled: PRR- is greater than 1 with at least 5 cases, and CPA method detects at least 2 successive change points of PRR- which made consecutively increasing segments. We tested this hypothesis by 95 test cases identified from a drug safety reference set and 2 validated signals from EudraVigilance database: CPA was applied on PRR-. For benfluorex and AVI, change points detected by CPA on PRR- were more meaningful compared with monthly counts of reports: More change points detected and detected earlier. In the reference set, 14 positive controls satisfied CPA hypothesis, 6 positive controls only met first requirements, 3 negative controls only met first requirement, and 2 validated signals satisfied CPA hypothesis. The combination of CPA and PRR represents a significant advantage in detecting earlier signals and reducing false-positive signals. This approach should be confirmed in further studies.

Retrograde administration of ultrasound-guided endovenous microfoam chemical ablation for the treatment of superficial venous insufficiency

ObjectiveThis study measured patient outcomes among symptomatic patients with superficial chronic venous insufficiency who were treated with retrograde ultrasound-guided polidocanol microfoam 1% in a community setting. MethodsBetween March 2015 and June 2017, 250 symptomatic patients with C2-C6 chronic venous insufficiency received polidocanol microfoam 1% and were followed for 16 ± 7 months. Sixteen of the 250 patients (6.4%) had skin ulcers, and 56 (22.4%) were treated previously with thermal or surgical interventions. All patients underwent a duplex ultrasound venous incompetence study to map perforators and veins to be treated. Incompetent veins were accessed with a micropuncture needle distal to the midthigh perforator, approximately 10 cm above the knee fold. The leg was then elevated 45°. Under ultrasound guidance, the incompetent greater saphenous vein was closed with polidocanol microfoam 1%. A second injection was administered through the same catheter directing the microfoam to flow in a retrograde fashion through the incompetent venous valves to the ankle. ResultsAll patients completed the initial treatment; 55 (22.0%) required planned secondary treatment during the follow-up period for residual venous reflux in the below-knee greater saphenous vein. Complete elimination of venous valvular reflux and symptom improvement was documented in 236 patients (94.4%). Minor adverse events included asymptomatic deep vein thrombi (n = 2), common femoral vein thrombus extension (n = 1), and superficial venous thrombi (n = 4). Of the 16 patients with skin ulcers, 10 were C6 patients and 80% experienced wound closure within 4 weeks of treatment. ConclusionsRetrograde administration of polidocanol microfoam 1% is a safe and effective treatment with important clinical benefit for superficial venous insufficiency in community practice.

Biaxial Mechanical Behavior of Bovine Saphenous Venous Valve Leaflets

Chronic venous disease is caused by chronic venous insufficiency (CVI), which results in significant symptoms such as venous ulcers, ankle eczema, leg swelling, etc. Venous valve incompetence is a major cause of CVI. When the valves of veins in the leg become incompetent (i.e., do not close properly), blood is able to flow backwards (i.e., reflux), which results in blood pooling in the lower extremities, distal venous hypertension, and CVI. Current clinical therapies, such as surgical venous valve reconstruction and bioprosthetic venous valve replacement, are highly invasive and only moderately successful. This is due, in part, to the scanty information available about venous valve leaflet structure and mechanical properties. To date, only one previous study by our research group has reported on the mechanical properties of venous valve leaflet tissue, and specifically in the case of jugular vein valves. In this study, we conducted equibiaxial tensile tests on bovine saphenous vein valve leaflet tissues to better understand their nonlinear, anisotropic mechanical behavior. By stretching the valvular tissues to 60% strain in both the circumferential and radial directions, we generated stress-strain curves for proximal (i.e., those closest to the heart) and distal (i.e., those furthest from the heart) valve leaflets. Histology and collagen assays were also conducted to study corresponding leaflet microstructures and the biochemical properties of the tissues. Results showed: (1) saphenous venous valve tissues possessed overall anisotropic properties. The tissues were stiffer in the circumferential direction than in the radial direction (p<0.01), and (2) saphenous venous valve tissues from the proximal end showed nonlinear isotropic mechanical properties, while those from the distal end showed nonlinear anisotropic mechanical properties. (3) Distal saphenous venous valve tissues appeared to be stiffer than proximal ones in the circumferential direction, p=0.04 (i.e., inter-valvular variability), and (4) the collagen concentration showed a decreasing trend from the proximal to the distal end. This study focuses on highly relevant animal (bovine) tissues to develop test protocols, establish biomechanical structure-function correlations, and to provide data critical to the design of clinical prosthetic venous valves. To the best of the author's knowledge, this is the first study reporting the biaxial mechanical properties of saphenous venous valve leaflet tissues and thus contributes toward refining our collective understanding of valvular tissue biomechanics.