VasQ U.S. pivotal study demonstrates the safety and effectiveness of an external vascular support for arteriovenous fistula creation.

OBJECTIVE: Arteriovenous fistula (AVF) creation is a commonly performed vascular operation that reports 6-month functional success rates as low as 50%. Recently, a nitinol external vascular support device, VasQ, has shown potential in studies outside the United States (U.S.) to improve AVF outcomes when implanted at creation. Here, the pivotal study results of this novel technology in treating patients in the U.S. are described. METHODS: VasQ was implanted in 144 patients at 16 centers across the U.S. who were referred for creation of a new AVF and consented for enrollment in a 2-year, prospective, multicenter, single-arm, open-label study. Brachiocephalic (n = 129) and radiocephalic (n = 15) AVFs were analyzed. The primary endpoint was primary patency at 6 months compared against a performance goal of 55% derived from a systematic literature search. Safety endpoints included device-related events, ischemic steal, infection, aneurysm, and seroma at up to 6 months. Minimum arterial size was 2.0 mm; target veins were required to measure 2.5 to 6 mm. Key exclusion criteria were patients <18 or >80 years, those with known ipsilateral central venous occlusion, target cannulation zone venous depth greater than 8 mm, and New York Heart Association class 3 or 4. RESULTS: Patients were 61% male, 53% White, 35% African American, and 14% Hispanic. Mean age was 60 years, and median body mass index was 30.4. Of the patients, 69% were diabetic, 66% were on dialysis at the time of creation, and 70% had a prior access surgery. At 6 months, steal was observed in 2.1%, infection in 0.7%, and no aneurysms or seromas were seen. Primary patency at 6 months was 66% (P < .021 vs performance goal). Physiological maturation was achieved in 92.4% of patients. Successful two-needle cannulation for patients that entered the study on dialysis was achieved in 88% of VasQ AVFs at a median of 56 days. Pre-dialysis patients who initiated dialysis during the study achieved two-needle cannulation in 81.6% VasQ AVFs. Interventions were required at a rate of 1.07 per patient year over the entire study period. Two-year cumulative patency was 76.6% (95% confidence interval, 67.9%-83.4%) with no statistical difference between patients requiring interventions and those that did not. No patency differences were observed between brachiocephalic and radiocephalic AVFs. CONCLUSIONS: The U.S. pivotal study results demonstrated improved AVF outcomes and an excellent safety profile with VasQ use relative to traditional AVFs. Under the conditions of this trial, VasQ shows great promise in expeditiously and efficiently enhancing AVF functional success.

The FACT : Use of a novel intermittent pneumatic compression device to promote pre-surgery arm vein dilation in patients with chronic renal failure.

BACKGROUND: Arteriovenous fistula (AVF) creation and maturation for hemodialysis is globally a topic of importance given the poor results and high costs associated with renal care. Successful AVF (surgical or endovascular) creation requires appropriate superficial veins and quality arteries. Many procedures fail due to initial small veins with limited blood flow capacity and distensibility. Intermittent pneumatic compression has previously shown success in trials to increase superficial veins in patients with end stage renal disease post AVF. The objective of this study is to investigate the role of an intermittent pneumatic device, the Fist Assist®, to dilate cephalic arm veins in patients with advanced chronic kidney disease (CKD) prior to AVF placement. METHODS: Three centers enrolled subjects from June 2019 through July 2021. Baseline Doppler measurements of the cephalic vein in standard locations the forearm and upper arm with and without a blood pressure cuff were recorded. Patients were instructed and used Fist Assist® on their non-dominant arm for up to 4 h daily for 90 days. At approximately 3 months, Doppler measurements were repeated. The primary endpoint was cephalic vein enlargement with secondary endpoints based on percentage of veins approaching 2.5 mm in the forearm and 3.5 mm in the upper arm. RESULTS: Thirty-seven subjects with CKD (mean eGFR 13.8 mL/min) were enrolled and completed the trial. Paired-difference t-tests (one tail) for aggregate data showed significant venous dilation of the cephalic vein in both the forearm and upper arm after use with the Fist Assist® (p < 0.05). Mean differences in the forearm veins were approximately 0.6 and 1.1 mm in the upper arm cephalic vein after Fist Assist® application. There were no major complications reported by any subject during the trial. CONCLUSIONS: Fist Assist® use in patients with CKD is effective to enhance vein dilation. Forearm and upper arm cephalic veins increased on average 0.6 and 1.1 mm respectively after Fist Assist® application. This is the first trial to evaluate the effect of intermittent, focal pneumatic compression on pre-surgery vein diameter in patients with advanced CKD before AVF creation.

PATENCY-2 trial of vonapanitase to promote radiocephalic fistula use for hemodialysis and secondary patency.

OBJECTIVE: Arteriovenous fistulas created for hemodialysis often fail to become usable and are frequently abandoned. This prospective trial evaluated the efficacy of vonapanitase, a recombinant human elastase, in increasing radiocephalic fistula use for hemodialysis and secondary patency. METHODS: PATENCY-2 was a randomized, double-blind, placebo-controlled trial in patients on or approaching the need for hemodialysis undergoing radiocephalic arteriovenous fistula creation. Of 696 screened, 613 were randomized, and 603 were treated (vonapanitase n = 405, placebo n = 208). The study drug solution was applied topically to the artery and vein for 10 min immediately after fistula creation. The primary endpoints were fistula use for hemodialysis and secondary patency (fistula survival without abandonment). Other efficacy endpoints included unassisted fistula use for hemodialysis, primary unassisted patency, fistula maturation and unassisted maturation by ultrasound criteria, and fistula procedure rates. RESULTS: The proportions of patients with fistula use for hemodialysis was similar between groups, 70% vonapanitase and 65% placebo, (p = 0.33). The Kaplan-Meier estimates of 12-month secondary patency were 78% (95% confidence interval [CI], 73-82) for vonapanitase and 76% (95% CI, 70-82) for placebo (p = 0.93). The proportions with unassisted fistula use for hemodialysis were 46% vonapanitase and 37% placebo (p = 0.054). The Kaplan-Meier estimates of 12-month primary unassisted patency were 50% (95% CI, 44-55) for vonapanitase and 43% (95% CI, 35-50) for placebo (p = 0.18). There were no differences in the proportion of patients with fistula maturation or in fistula procedure rates. Adverse events were similar between groups. Vonapanitase was not immunogenic. CONCLUSIONS: Vonapanitase treatment did not achieve clinical or statistical significance to meaningfully improve radiocephalic fistula surgical outcomes. Outcome in the placebo group were better than in historical controls. Vonapanitase was well-tolerated and safe. TRIAL REGISTRATION: clinicaltrials.gov: NCT02414841 (https://clinicaltrials.gov/ct2/show/NCT02414841).

Creating arteriovenous fistulas for children in Guatemala.

OBJECTIVE: The Guatemalan Foundation for Children with Kidney Diseases was established in 2003 as the first and only comprehensive pediatric nephrology program and hemodialysis unit in Guatemala. Bridge of Life (BOL) is a not-for-profit charitable organization focused on chronic kidney disease and supplied equipment, training and support during formation of the hemodialysis unit. Pediatric permanent vascular access (VA) expertise had not been established and noncuffed dialysis catheters provided almost all VA, many through subclavian vein access sites. BOL assistance was requested for establishing a VA surgical program, resulting in recurring BOL surgical missions to create arteriovenous fistulas (AVF) in these children. This study analyzes the BOL pediatric VA missions to Guatemala. METHODS: Three surgical pediatric VA missions were conducted in Guatemala from 2015 to 2017. Each mission was led by two or three surgeons. All supplies and equipment (including ultrasound units) were taken as part of each mission. The BOL surgical VA mission teams work with local pediatric surgeons, pediatric nephrologists, and dialysis nurses to establish collegial relationships and foster teaching interactions. We retrospectively reviewed the patient demographic data, procedures, and outcomes for these missions. RESULTS: AVFs were created in 54 new pediatric patients. Ages were 8 to 19 years (13.4 ± 2.8 years) and 29 patients (54%) were male. Patient weights were 28 to 50 kg (30.8 ± 8.3 kg) with body mass indexes of 12 to 25 kg/m2 (17.9 ± 2.9 kg/m2). Radiocephalic AVFs were created in 21 children (39%), proximal radial artery AVFs in 12 (22%). and brachial artery inflow AVFs in 5 (9%). Sixteen patients (30%) required transpositions and one a translocation; two of these were femoral procedures. Primary and cumulative patency rates were 83% and 85% at 12 months and 62% and 85% at 36 months, respectively. The median follow-up was 17 months. Interventions with fistulagram and balloon angioplasty options were not available for AVF dysfunction or access salvage during the study period. However, six patients underwent an AVF revision and salvage during subsequent missions or by one of the Guatemalan surgeons (R.S.). Four individuals underwent successful transplantation during the study period. There were no operative deaths or major complications. CONCLUSIONS: Pediatric VA missions to Guatemala created safe and functional AVFs in concert with local pediatric surgeons and pediatric nephrologists. Three surgical missions included access operations in 54 new patients. Cumulative AVF patency was 85% at 36 months.

ENU induced mutations causing congenital cardiovascular anomalies.

We used non-invasive high frequency ultrasound to screen N-ethyl-N-nitrosourea mutagenized mouse fetuses for congenital cardiovascular anomalies. We ultrasound scanned 7546 mouse fetuses from 262 mutagenized families, and identified 124 families with cardiovascular defects. Represented were most of the major congenital cardiovascular anomalies seen clinically. The ENU-induced mutations in several families were mapped using polymorphic microsatellite DNA markers. One family with forelimb anomalies and ventricular septal defects, phenotypes similar to Holt-Oram syndrome, and one family with transposition of the great arteries and heart situs anomalies were mapped to different regions of mouse chromosome 4. A third mutation causing persistent truncus arteriosus and craniofacial defects, phenotypes reminiscent of DiGeorge syndrome, was mapped to mouse chromosome 2. We note that mouse chromosomes 4 and 2 do not contain Tbx5 or Tbx1, genes previously linked to Holt-Oram and DiGeorge syndromes, respectively. In two other families, the ENU-induced mutation was identified--Sema3CL605P was associated with persistent truncus arteriosus with interrupted aortic arch, and the Gja1W45X connexin43 mutation caused conotruncal malformation and coronary aneurysms. Although our screen was designed as a recessive screen, a number of the mutations showed cardiovascular phenotypes in both heterozygote and homozygote animals. These studies show the efficacy of ENU mutagenesis and high-throughput ultrasound phenotyping in recovering mutations causing a wide spectrum of congenital heart defects. These ENU-induced mutations hold promise in yielding new insights into the genetic basis for human congenital heart disease.