Investigational Device Exemption Research Articles

Prospective assessment of dynamic changes in frailty and its impact on early clinical outcomes following physician-modified fenestrated-branched endovascular repair of complex abdominal and thoracoabdominal aortic aneurysms

IntroductionFrailty, a predictor of poor outcomes, has been widely studied as a screening tool in surgical decision-making. However, the impact of frailty on the outcomes after fenestrated-branched endovascular aortic repairs (FBEVARs) is less well established. In addition, the changes in frailty during recovery after FBEVAR are unknown. We aim to assess the impact of frailty on outcomes of high-risk patients undergoing physician-modified FBEVARs for complex abdominal and thoracoabdominal aortic aneurysms, as well as the changes in frailty during follow-up. MethodsConsecutive patients enrolled in a single-center prospective Physician-Sponsored Investigational Device Exemption protocol (FDA# G200159) were evaluated. In addition to the baseline characteristics, frailty was assessed using the Hopkins Frailty Score (HFS) and frailty index (FI) measured by the Frailty Meter. Sarcopenia was measured by L3 total psoas muscle area (PMA). These measurements were repeated during follow-up. The follow-up HFS and FI were compared with baseline scores using the Wilcoxon signed-rank test, whereas follow-up PMA measurements were compared with the baseline using the paired t test. The association between baseline frailty and morbidity was evaluated by the Wilcoxon rank-sum test. ResultsSeventy patients were analyzed in a prospective Physician-Sponsored Investigational Device Exemption study from February 9, 2021, to June 2, 2023. At baseline, HFS identified 54% of patients as not frail, 43% as intermediately frail, and 3% as frail. Technical success of FBEVAR was 94% with one in-hospital mortality. Early major adverse events were seen in 10 (14.3%) patients. No difference in baseline FI was seen between patients with early morbidity and those without. Patients who were not frail per HFS were less likely to experience early morbidity (P = .033), and there was a significantly lower baseline PMA in patients who experienced early morbidity (P = .016). At 1 month, patients experienced a significant increase in HFS and HFS category (P = .001 and P = .01) and a significant decrease in sarcopenia (mean PMA: −96 mm2, P = .005). At 6 months, HFS and HFS category as well as PMA returned toward baseline (P = .42, P = .38, and mean PMA: +4 mm2, P = .6). ConclusionsPreoperative frailty and sarcopenia were associated with early morbidity after physician-modified FBEVAR. During follow-up, patients became more frail and sarcopenic by 1 month. Recovery from this initial decline was seen by 6 months, suggesting that frailty and sarcopenia are reversible processes rather than a unidirectional phenomenon of continued decline.

Safety and effectiveness of the first contact force ablation catheter with a flexible tip

Catheter ablation is an established therapy for paroxysmal atrial fibrillation (PAF). The TactiFlex Ablation Catheter, Sensor Enabled (TactiFlex SE) is a next-generation radiofrequency ablation catheter incorporating fiber optics-based contact force-sensing technology with a flexible, laser-cut tip. The study sought to evaluate the safety and effectiveness of the TactiFlex SE ablation catheter for treatment of drug-refractory PAF. The TactiFlex AF investigational device exemption was a prospective, nonrandomized, multicenter clinical study. Enrollment began on June 26, 2020 and completed June 18, 2021. Subjects with PAF underwent de novo pulmonary vein isolation and, if indicated, ablation for typical atrial flutter. Subjects were followed for 12 months. Of the 355 subjects enrolled at 37 sites worldwide, 334 underwent ablation with the TactiFlex SE catheter. The Kaplan-Meier estimate of 12-month freedom from AF/atrial flutter (AFL)/atrial tachycardia recurrence was 72.9% (95% confidence interval [CI] 95% CI 67.2%-77.8%) and clinical success was 83.6% (95% CI 95% CI 78.1%-87.2%). As-treated analyses compared subjects treated at high power (left atrium time-averaged power setting 40-50 W; n = 222) vs low power (<40 W; n = 97). The Kaplan-Meier estimate of 12-month freedom from AF/AFL/atrial tachycardia recurrence was 76.4% (95% CI 69.3%-82.0%) and clinical success was 83.9% (95% CI 77.5%-88.6%) in the high-power group compared with 66.8% (95% CI 56.1%-75.5%) and 80.7% (95% CI 70.8%- 87.5%), respectively, in the low-power group. The primary safety event rate in all treated subjects was 4.3%; 4.1% in the HP group and 5.2% in the LP group (P = .7671). TactiFlex SE is safe and effective for treatment of drug-refractory PAF and concomitant AFL and enables more efficient procedures than previous generation catheters.

Safety and learning curve of percutaneous axillary artery access for complex endovascular aortic procedures

BackgroundPercutaneous axillary artery access is increasingly used for large-bore access during interventional vascular and cardiac procedures. The aim of this study was to evaluate the safety and learning curve of percutaneous axillary artery access in patients undergoing complex endovascular aortic repair (fenestrated and branched endovascular aneurysm repair [FBEVAR]) requiring large-bore upper extremity access and to discuss best practices for technique and complication management. MethodsOne-hundred forty-six patients undergoing large-bore percutaneous axillary artery access during FBEVAR in a prospective, nonrandomized, Investigational Device Exemption study between September 2017 and January 2023 were analyzed. Ultrasound guidance and micropuncture were used to access the second portion of the axillary artery and 2 Perclose Proglide or Prostyle devices (Abbott Vascular) were predeployed before the insertion of the large-bore sheath. Completion angiography was performed in all patients to verify hemostatic closure. Axillary artery patency was also assessed on follow-up computed tomography angiography. Patient-related, procedural, and postoperative variables were collected and analyzed. ResultsOne-hundred forty-five patients underwent successful percutaneous axillary artery access; 1 patient failed axillary access and alternative access was established. The left axillary artery was accessed in 115 patients (79%), and the right axillary artery was accessed in 30 patients (21%). The largest profile sheath was 14 F in 4 patients (2.8%), 12F in 133 patients (91.7%), and 8F in 8 patients (5.5%). Ten patients (6.9%) required covered stent placement (Viabahn, W. L. Gore & Associates) for failure to achieve hemostasis; there were no conversions to open surgical repair. Additional adverse events included transient upper extremity weakness in two patients (1.3%) and transient upper extremity paresthesias in two patients (1.3%). Three patients (2%) suffered postoperative strokes, including one unrelated hemorrhagic stroke and two possibly access-related embolic strokes. On follow-up, axillary artery patency was 100%. There was a trend toward decreased closure failure over time, with seven patients (10%) in the early cohort and three (4%) in the late cohort. There was a significant negative correlation between the cumulative complication rate and the cumulative experience. ConclusionsLarge-bore percutaneous axillary artery access provides safe upper extremity large-bore access during FBEVAR, achieving successful closure in >90% of patients with a low incidence of access-related complications. There was a trend toward better closure rates with increasing experience, suggesting a learning curve effect. Application of best practices including ultrasound guidance and angiography may ensure safe application of the technique of percutaneous large-bore axillary artery access.

EsophAguS Deviation During RadiofrequencY Ablation of Atrial Fibrillation: The EASY AF Trial

BackgroundInjury to the esophagus has been reported in a high percentage of patients undergoing ablation of atrial fibrillation (AF). ObjectivesThis study assessed the incidence of esophageal injury in patients undergoing ablation of AF with and without an esophageal deviating device. MethodsThis prospective, randomized, multicenter, double-blinded, controlled Food and Drug Administration investigational device exemption trial compared the incidence of ablation-related esophageal lesions, as assessed by endoscopy, in patients undergoing AF ablation assigned to a control group (luminal esophageal temperature [LET] monitoring alone) compared with patients randomized to a deviation group (esophagus deviation device + LET). This novel deviating device uses vacuum suction and mechanical deflection to deviate a segment of the esophagus, including the trailing edge. ResultsThe data safety and monitoring board recommended stopping the study early after randomizing 120 patients due to deviating device efficacy. The primary study endpoint, ablation injury to the esophageal mucosa, was significantly less in the deviation group (5.7%) in comparison to the control group (35.4%; P < 0.0001). Control patients had a significantly higher severity and greater number of ablation lesions per patient. There was no adverse event assigned to the device. By multivariable analysis, the only feature associated with reduced esophageal lesions was randomization to deviating device (OR: 0.13; 95% CI: 0.04-0.46; P = 0.001). Among control subjects, there was no difference in esophageal lesions with high power/short duration (31.8%) vs other radiofrequency techniques (37.2%; P = 0.79). ConclusionsThe use of an esophageal deviating device resulted in a significant reduction in ablation-related esophageal lesions without any adverse events.

Stemless Reverse Shoulder Arthroplasty.

Since the Food and Drug Administration (FDA) approval nearly two decades ago, the indications for and utilization of reverse shoulder arthroplasty (RSA) have expanded considerably. Stemless RSA designs have been used in Europe since 2005, but have only recently been introduced in domestic Investigational Device Exemption trials. Potential advantages of stemless RSA are similar to those of stemless anatomic total shoulder arthroplasty, which may include fewer shaft-related complications, avoidance of stress shielding, bone preservation, and easier revision surgery. European data support similar outcomes between certain stemless RSA prostheses compared with that of stemmed RSA implants at early and mid-term follow-up. However, long-term outcomes remain to be seen and differences exist between the stemless RSA designs used in Europe and those being studied in domestic clinical trials. An understanding of the potential advantages and disadvantages of stemless RSA, differences between existing designs, and reported clinical outcomes is prudent for the safe and meaningful implementation of this new technology in the United States.

Branched stented anastomosis frozen elephant trunk repair: Early results from a physician-sponsored investigational device exemption study

BackgroundMultisegment thoracic aortic disease typically requires total aortic arch replacement, affects a heterogenous population, and carries a high risk even at centers of excellence. Risk has been associated with the duration of operation and complexity of repair. A novel branched stented anastomosis frozen elephant trunk repair (B-SAFER) technique has been developed at our center and is currently being studied as a physician-sponsored investigation device exemption (PS-IDE). ObjectiveThis study aimed to assess the early safety of using this investigational technique to treat the proximal aorta in subjects with aortic disease involving multiple segments. MethodsThis prospective, single center, nonrandomized study enrolled patients undergoing B-SAFER for acute aortic syndrome (n = 73), aortic aneurysm with chronic aortic dissection (n = 68), degenerative aortic aneurysm (n = 33), or congenital aortic arch disease (n = 4). Devices are delivered antegrade under hypothermic circulatory arrest, and the arch reconstruction is performed as a single anastomosis single stent (SASS; n = 70), single anastomosis multiple stent (SAMA; n = 68), multiple anastomosis single stent (MASS; n = 21), or multiple anastomosis multiple stent (MAMS; n = 16) reconstruction. The primary safety endpoints were operative mortality, disabling stroke, and paraparesis/paralysis. ResultsBetween May 27, 2021, and December 31, 2022, 178 patients underwent B-SAFER in the configurations and for the indications as described above. The median patient age was 65 years (range, 21 to 85 years), and 52 (29%) were female. The median cardiopulmonary bypass time was 188 minutes (interquartile range [IQR], 155 to 226 minutes), and 97% of the patients underwent repair with antegrade brain perfusion for a median of 46 minutes (IQR, 38 to 61 minutes). Operative mortality occurred in 10 patients (5.6%, including 6 [8.2%] with acute dissection, 2 [2.9%] with chronic dissection, 2 [6.1%] with degenerative aneurysm, and 0 with a congenital disorder), disabling stroke in 5 patients (2.9%), and paraparesis in 1 patient. Other serious complications included respiratory failure (n = 20; 11.4%) and acute kidney injury (n = 18; 10%). Thirty-two patients (18%) had undergone second-stage repairs (28 endovascular and 4 open), with 1 operative mortality after that procedure due to distal rupture. Estimated survival was 95% at 30 days, 88% at 90 days, 84% at 6 months, and 79% at 1 year. One-year survival differed by indication (72% for acute dissection, 91% for chronic dissection, 71% for degenerative aneurysm, and 100% for congenital disorders). Conclusions:The B-SAFER technique for total arch replacement in a complex cohort of patients with various indications for surgery is a safe and reproducible operation, as demonstrated by the early results from a very inclusive PS-IDE study. Further follow-up and analysis will help refine the technique. Novel devices to perform this procedure should be developed.

Technical Infrastructure for Clinical Translation of Electron FLASH

For safe clinical translation of electron FLASH, hardware tools for real-time beam control and software tools for treatment planning are necessary. The purpose of this study is to prototype high-throughput hardware for real-time beam control, along with accurate beam modeling of a modern clinical Linac configured to deliver FLASH dose-rates. For real-time beam current monitoring, a beam current transformer (BCT) was initially coupled to a fast digitizer and its linearity was established by varying dose per pulse. The radiation pulse width was modified, and this change was measured using the BCT. The BCT was then used to measure the variability of dose per pulse and pulse width due to a mistuned linear accelerator system. Next, the BCT was interfaced with a field programmable gate array (FPGA) which provides the ability for high-throughput and deterministic control of the Linac based on dose accumulation. For beam modeling, the program, TOol for PArticle Simulation (TOPAS), was used to obtain beam parameters by using Bayesian optimization of the beam energy, source size, angular, and energy spread via comparison of simulated and representative dose profiles. The beam model would then be employed to calculate 3D dose distribution in a CT scan of a 3D-printed anatomically realistic mouse phantom. The area under the current-time curve from the BCT exhibited excellent linearity (response = 12.80 nC/Gy) up to 2.5 Gy/Pulse (R2 = 0.99). The peak beam current for the electron FLASH beam was measured to be ∼10 mA for an instantaneous dose-rate of ∼5×105 Gy/s. The measured radiation pulse width agreed with the expected value (3.7 μs). The pulse width was then shortened and the measurement by the BCT indicated pulse widths of 1.8 μs and 0.5 μs corresponding to 0.7 Gy/pulse and 0.3 Gy/pulse, respectively. The beamline exhibited a ramp-up in dose per pulse and pulse width when using the automatic frequency controller (AFC). For the first pulse, the dose delivered was ∼0.1-0.3 Gy and the pulse width was 0.6 μs. The output stabilized to nominal values of dose and pulse width after 3-4 pulses. This ramp-up was mitigated by manually tuning the RF resonance with the AFC disabled, after which the BCT exhibited constant output and pulse width. The beam modeling work is in progress. We demonstrated that a BCT can provide real-time measurement of per-pulse output suitable as input for FLASH beam control based on dose accumulation. The next steps are to quantify the accuracy of the dose control mechanism with the FPGA-based hardware. Potential failure modes will be identified and mitigated in parallel with the development of the hardware. A 3D-printed mouse phantom has been constructed to facilitate beam modeling work for treatment planning (in progress). On completion of this work, it is expected that we will have key infrastructure elements needed to move towards an eventual FDA investigational device exemption for clinical trials.

Current and Expanded Indications for Cervical Disc Arthroplasty: Beyond the FDA IDE Studies.

The widespread success of cervical disc arthroplasty (CDA) has led to an interest in expanding indications beyond those outlined in the initial Food and Drug Administration investigational device exemption studies. Some of these off-label indications currently include 3-level and 4-level CDA, hybrid constructs with adjacent segment anterior cervical discectomy and fusion or corpectomy constructs, pre-existing kyphosis, revision of a failed anterior cervical discectomy and fusion to a CDA, CDA in the setting of significant degenerative disc disease and/or facet joint arthropathy, CDA for congenital cervical stenosis, and CDA in the presence of ossification of the posterior longitudinal ligament. This review article will summarize the current literature pertaining to the aforementioned indications.

OS09.5.A BREAKING DOWN BARRIERS: THE IMPACT OF BLOOD-BRAIN BARRIER DISRUPTION ON THE GLIOMA METABOLIC MICROENVIRONMENT, IN SITU

Abstract BACKGROUND The microenvironment of glioblastoma is complex and defined in part by protumorigenic metabolic changes. Within this microenvironment, blood-brain barrier disruption is often associated with the most aggressive portions of the tumor. To date, the metabolic tumor microenvironments of enhancing, blood-brain barrier (BBB) disrupted portions of gliomas, as compared to BBB-intact tumor, remain poorly understood. Specifically, it is unclear if the associated blood-brain barrier disruption merely reflects or functionally supports tumor aggressiveness. METHODS Intra-operative high-molecular weight microdialysis was utilized under an investigational device exemption (NCT NCT04047264) to sample the extracellular metabolome of radiographically diverse regions during fifteen neurosurgical resections. The global extracellular metabolome of recovered microdialysate from contrast-enhancing and non-enhancing tumor, as well as brain adjacent to tumor, was evaluated via ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) on the Metabolon platform and assessed using enrichment and correlation analyses. RESULTS Among 162 named metabolites identified via ultra-performance liquid chromatography tandem mass spectrometry, a novel glioma-associated metabolite, guanidinoacetate (GAA), was 126.32x higher in enhancing tumor than in adjacent brain and 13.63x higher in non-enhancing tumor than brain. Forty-eight additional metabolites were 2.05-10.18x more abundant in enhancing tumor than brain, including carnitine family members and all nine large neutral amino acids. Except for GAA and 2-hydroxyglutarate in IDH-mutant gliomas, differences between non-enhancing tumor and brain microdialysate were comparatively modest and less consistent, suggesting heterogeneity in the glioma metabolic microenvironment of blood-brain barrier (BBB) intact areas as compared to BBB-disrupted portions of gliomas. Interestingly, the enhancing but not the non-enhancing glioma metabolome was significantly enriched for plasma-associated metabolites, largely comprising amino acids and carnitines. CONCLUSION Our patient-derived data suggest that the BBB-disrupted metabolome of high-grade gliomas is characterized by metabolite diffusion from circulation into the tumor microenvironment. Further studies are ongoing to determine how this alteration in the glioma extracellular metabolome impacts glioma behavior and how it could be therapeutically targeted via BBB-modulating drugs.

Seven-year outcomes following aortic valve replacement with a novel tissue bioprosthesis

ObjectiveAs bioprosthetic aortic valve replacement (AVR) extends to younger cohorts, tissue durability is of paramount importance. We report 7-year outcomes from an AVR bioprosthesis utilizing novel tissue. MethodsThis was an international investigational device exemption trial for novel AVR with annual follow-up and a subset re-consented at 5 years for extended 10-year follow-up. Safety end points and echocardiographic measurements were adjudicated by an independent clinical events committee and by a dedicated core laboratory, respectively. ResultsBetween January 2013 and March 2016, 689 patients underwent AVR with the study valve. Mean age was 66.9 ± 11.6 years, Society of Thoracic Surgeons risk score was 2.0% ± 1.8%, and 74.3% of patients were New York Heart Association functional class II and III. Five-year follow-up was completed by 512 patients, and 225 re-consented for extended follow-up. Follow-up duration was 5.3 ± 2.2 years (3665.6 patient-years), and 194 and 195 patients completed 6- and 7-year follow-ups, respectively. One-, 5-, and 7-year freedom from all-cause mortality was 97.7%, 89.4%, and 85.4%, respectively. Freedom from structural valve deterioration at 7 years was 99.3%. At 7 years, effective orifice area and mean gradients were 1.82 ± 0.57 cm2 (n = 153), and 9.4 ± 4.5 mm Hg (n = 157), respectively. At 7 years, predominantly none (96.8% [152 out of 157]) or trivial/trace (2.5% [4 out of 157]) paravalvular regurgitation and none (84.7% [133 out of 157]) or trivial/trace (11.5% [18 out of 157]) transvalvular regurgitation were observed. ConclusionsWe report the longest surgical AVR follow-up with novel tissue in an investigational device exemption trial utilizing an independent clinical events committee and an echocardiography core laboratory. This tissue demonstrates excellent outcomes through 7 years and is the benchmark for future surgical and transcatheter prostheses.

Validation of a 12-color flow cytometry assay for acute myeloid leukemia minimal/measurable residual disease detection.

Acute myeloid leukemia (AML) minimal/measurable residual disease (MRD) by multicolor flow cytometry is a complex laboratory developed test (LDT), challenging for implementation. We share our experience in the validation of a 12-color AML MRD flow cytometry assay to meet stringent regulatory requirements. We worked under the guidelines of the CLSI HL62 publication, illustrated the details of the validation process that was tailored to uniqueness of AML MRD, and tested its clinical validity in 61 patients. The "trueness" was determined by correlating with concurrent molecular genetic testing and follow-up bone marrow examinations. Under assay specificity, we shared the details of panel design, analysis, and criteria for interpretation and reporting. The assay accuracy was assessed by testing known positive and negative samples and correlating with molecular genetic testing and follow-up bone marrow examination. The limit of detection (LOD) and limit of quantification (LOQ) were validated to a level between 0.01% and 0.1%, varied from the leukemia-associated immunophenotypes (LAIP) and the numbers of events obtained for analysis. Assay linearity, precision and carry over studies all met acceptable criteria. In the clinical validity test, the concordance was 93%, specificity 98% and sensitivity 83%. The most challenging aspects of the assay were the discrimination of pre-leukemic cells (persistent clonal hematopoiesis) or underlying myelodysplastic clones from AML MRD with immunophenotypic switch or subclone selection. The validation met all criteria and obtained FDA IDE (investigational device exemption) approval. This study provides ample technical and professional details in setting up the AML MRD flow cytometry assay and illustrates through the example of the "fit for purpose" validation process. We also highlight the need for further characterization of abnormal blasts bearing the potential for AML relapse.

Rationale and design of an implant procedure and pivotal study to evaluate safety and effectiveness of Medtronic's tibial neuromodulation device

Percutaneous tibial neuromodulation is a medical guideline recommended therapy for treating symptoms of overactive bladder. Stimulation is delivered to the tibial nerve via a thin needle placed percutaneously for 30 min once a week for 12-weeks, and monthly thereafter. Studies have shown that this therapy can effectively relieve symptoms of overactive bladder; however, the frequent office visits present a barrier to patients and can impact therapy effectiveness. To mitigate the burden of frequent clinic visits, small implantable devices are being developed to deliver tibial neuromodulation. These devices are implanted during a single minimally invasive procedure and deliver stimulation intermittently, similar to percutaneous tibial neuromodulation. Here, we describe the implant procedure and design of a pivotal study evaluating the safety and effectiveness for an implantable tibial neuromodulation device. The Evaluation of Implantable Tibial Neuromodulation (TITAN 2) pivotal study is a prospective, multicenter, investigational device exemption study being conducted at up to 30 sites in the United States and enrolling subjects with symptoms of overactive bladder.

3-Year Outcomes From the Amplatzer Amulet Left Atrial Appendage Occluder Randomized Controlled Trial (Amulet IDE)

BackgroundThe Amulet (Abbott) left atrial appendage occluder investigational device exemption trial is the largest randomized trial evaluating the safety and effectiveness of the Amulet left atrial appendage occluder compared with the Watchman 2.5 device (Boston Scientific) through 5 years. ObjectivesThis analysis evaluated the device effect on 3-year outcomes in the Amulet investigational device exemption trial. MethodsThe medication regimen and key clinical outcomes were reported through 3 years including: 1) the composite of ischemic stroke or systemic embolism (SE); 2) the composite of all strokes, SE, or cardiovascular (CV) death; 3) major bleeding; and 4) all-cause death and CV death. ResultsA total of 1,878 patients at 108 sites were randomized. A significantly higher percentage of patients were free of oral anticoagulation usage at 3 years with Amulet (96.2%) vs Watchman (92.5%) (P < 0.01). Clinical outcomes were comparable for the composite of ischemic stroke or SE (5.0% vs 4.6%; P = 0.69); the composite of all strokes, SE, or CV death (11.1% vs 12.7%; P = 0.31); major bleeding (16.1% vs 14.7%; P = 0.46); all-cause death (14.6% vs 17.9%; P = 0.08); and CV death (6.6% vs 8.5%; P = 0.14) for Amulet and Watchman, respectively. Through 3 years, device factors (device-related thrombus or peridevice leak ≥3 mm) preceded ischemic stroke events and CV deaths more frequently in Watchman compared with Amulet patients. ConclusionsThe Amulet occluder demonstrated continued safety and effectiveness with over 96% free of oral anticoagulation usage through 3 years in a high-risk population compared to the Watchman device. (AMPLATZER Amulet LAA Occluder Trial [Amulet IDE]; NCT02879448)

Safety and effectiveness of the Woven EndoBridge (WEB) system for the treatment of wide necked bifurcation aneurysms: final 5 year results of the pivotal WEB Intra-saccular Therapy study (WEB-IT)

IntroductionThe US Woven EndoBridge Intra-saccular Therapy (WEB-IT) study is a pivotal, prospective, single arm, investigational device exemption study to evaluate the safety and effectiveness of the WEB device for the...

Severity of acute kidney injury is associated with decreased survival after fenestrated and branched endovascular aortic aneurysm repair

ObjectiveAcute kidney injury (AKI) occurs frequently in complex aortic surgery and has been implicated in perioperative and long-term survival. This study sought to characterize the relationship between AKI severity and mortality after fenestrated and branched endovascular aortic aneurysm repair (F/B-EVAR). MethodsConsecutive patients enrolled by the US Aortic Research Consortium in 10, prospective, nonrandomized, physician-sponsored investigational device exemption studies evaluating F/B-EVAR, between 2005 and 2023, were included in this study. Perioperative AKI during hospitalization was defined by and staged using the 2012 Kidney Disease Improving Global Outcomes criteria. Determinants of AKI were evaluated with backward stepwise mixed effects multivariable ordinal logistic regression. Survival was analyzed with conditionally adjusted survival curves and backward stepwise mixed effects Cox proportional hazards modelling. ResultsIn the study period, 2413 patients with a median (interquartile range [IQR]) age of 74 years (IQR, 69-79 years) underwent F/B-EVAR. The median follow-up duration was 2.2 years (IQR, 0.7-3.7 years). The median baseline estimated glomerular filtration rate (eGFR) and creatinine were 68 mL/min/1.73 m2 (IQR, 53-84 mL/min/1.73 m2) and 1.1 mg/dL (IQR, 0.9-1.3 mg/dL), respectively. Stratification of AKI identified 316 patients (13%) with stage 1 injury, 42 (2%) with stage 2 injury, and 74 (3%) with stage 3 injury. Renal replacement therapy was initiated during the index hospitalization in 36 patients (1.5% of cohort, 49% of stage 3 injuries). Thirty-day major adverse events were associated with AKI severity (all P ≤ .0001). Multivariable predictors of AKI severity included baseline eGFR (proportional odds ratio, 0.9 per 10 mL/min/1.73 m2 [95% confidence interval (CI), 0.85-0.95 per 10 mL/min/1.73 m2]; P < .0001), baseline serum hematocrit (0.58 per 10% [95% CI, 0.48-0.71 per 10%]; P < .0001), renal artery technical failure during aneurysm repair (3 [95% CI,1.61-5.72]; P = .0006), and total operating time (1.05 per 10 minutes [95% CI, 1.04-1.07 per 10 minutes]; P < .0001). One-year unadjusted survivals for AKI severity strata were 91% (95% CI, 90%-92%) for no injury, 80% (95% CI, 76%-85%) for stage 1 injury, 72% (95% CI, 59-87%) for stage 2 injury, and 46% (95% CI, 35-59%) for stage 3 injury (P<.0001). Multivariable determinants of survival included AKI severity (stage 1, hazard ratio [HR], 1.6 [95% CI, 1.3-2]); stage 2, HR, 2.2 [95% CI, 1.4-3.4]); stage 3 HR, 4 [95% CI, 2.9-5.5]; P < .0001), decreased eGFR (HR, 1.1 [95% CI, 0.9-1.3]; P = .4), patient age (HR, 1.6 per 10 years [95% CI, 1.4-1.8 per 10 years]; P < .0001), baseline chronic obstructive pulmonary disease (HR, 1.5 [95% CI, 1.3-1.8]; P < .0001), baseline congestive heart failure (HR, 1.7 [95% CI, 1.6-2.1]; P < .0001), postoperative paraplegia (HR, 2.1 [95% CI, 1.1-4]; P = .02), and procedural technical success (HR, 0.6 [95% CI, 0.4-0.8]; P = .003). ConclusionsAKI, as defined by the 2012 Kidney Disease Improving Global Outcomes criteria, occurred in 18% of patients after F/B-EVAR. Greater severity of AKI after F/B-EVAR was associated with decreased postoperative survival. The predictors of AKI severity identified in these analyses suggest a role for improved preoperative risk mitigation and staging of interventions in complex aortic repair.

Mid-Term Outcomes of "Complete Aortic Repair": Surgical or Endovascular Total Arch Replacement With Thoracoabdominal Fenestrated-Branched Endovascular Aortic Repair.

To describe a single-center experience of "complete aortic repair" consisting of surgical or endovascular total arch replacement/repair (TAR) followed by thoracoabdominal fenestrated-branched endovascular aortic repair (FB-EVAR). We reviewed 480 consecutive patients who underwent FB-EVAR with physician-modified endografts (PMEGs) or manufactured stent-grafts between 2013 and 2022. From those, we selected only patients treated with open or endovascular arch repair and distal FB-EVAR for aneurysms involving the ascending, arch and thoracoabdominal aortic segments (zones 0-9). Manufactured devices were used under an investigational device exemption protocol. Endpoints included early/in-hospital mortality, mid-term survival, freedom from secondary intervention, and target artery instability. There were 22 patients, 14 men and 8 women with a median age of 72±7 years. Thirteen postdissection and 9 degenerative aortic aneurysms were repaired with a mean maximum diameter of 67±11 mm. Time from index aortic procedure to aneurysm exclusion was 169 and 270 days in those undergoing 2- and 3-stage repair strategies, respectively. The ascending aorta and aortic arch were treated with 19 surgical and 3 endovascular TAR procedures. Three (16%) surgical arch procedures were performed elsewhere, and perioperative details were unavailable. Mean bypass, cross-clamp, and circulatory arrest times were 295±57, 216±63, and 46±11 minutes, respectively. There were 4 major adverse events (MAEs) in 2 patients: both required postoperative hemodialysis, 1 had postbypass cardiogenic shock necessitating extracorporeal membrane oxygenation, and the other required evacuation of an acute-on-chronic subdural hematoma. Thoracoabdominal aortic aneurysm repair was performed with 17 manufactured endografts and 5 PMEGs. There was no early mortality. Six (27%) patients experienced MAEs. There were 4 (18%) cases of spinal cord injury with 3 (75%) experiencing complete symptom resolution before discharge. Mean follow-up was 30±17 months in which there were 5 patient deaths-0 aortic related. Eight patients required ≥1 secondary intervention, and 6 target arteries demonstrated instability (3 IC, 1 IIIC endoleaks; 2 TA stenoses). Kaplan-Meier 3-year estimates of patient survival, freedom from secondary intervention, and target artery instability were 78±8%, 56±11%, and 68±11%, respectively. Complete aortic repair with staged surgical or endovascular TAR and distal FB-EVAR is safe and effective with satisfactory morbidity, mid-term survival, and target artery outcomes. The presented study demonstrates that repair of the entirety of the aorta - via total endovascular or hybrid means- is safe and effective with low rates of spinal cord ischemia. Cardiovascular specialists within comprehensive aortic teams at should feel confident that staged repair of the most complex degenerative and post-dissection thoracoabdominal aortic aneurysms can be safely performed in their patients with complication profile similar to that of less extensive repairs. Meticulous and intentional case planning is imperative for immediate and long-term success.

Predictors and outcomes of spinal cord injury following complex branched/fenestrated endovascular aortic repair in the US Aortic Research Consortium: Presented at the 2021 European Society for Vascular Surgery Meeting, Rotterdam, the Netherlands, September 28-29, 2021.

Objective: Spinal cord ischemia (SCI) is a well-known complication of thoracoabdominal aortic aneurysm repair and is associated with profound morbidity and mortality. The purpose of this study was to describe predictors for the development of SCI, as well as outcomes for patients who develop SCI, after branched/fenestrated endovascular aortic repair in a large cohort of centers with adjudicated physician-sponsored investigational device exemption studies.

Impact of Using Endografts From Multiple Manufacturers on the Mid-term Outcomes of Physician-Modified Fenestrated-Branched Endovascular Aneurysm Repair

Complex endovascular aortic repairs can involve interactions of multiple aortic endografts from different device manufacturers. This may be due to the repair of failed previous endografts, intentional staging of extensive thoracoabdominal aortic repairs, and different manufacturers offering distinct device features suitable for specific purposes. However, there are limited data evaluating the interactions between aortic components from different manufacturers and their impact on clinical outcomes. Thus, we evaluated the impact of mixing aortic endografts from multiple manufacturers by comparing the rate of type IIIA endoleaks and clinical outcomes after physician-modified fenestrated-branched endovascular aortic repairs (PM-FBEVAR) using endografts from a single vs multiple manufacturers. A single-institution retrospective review of consecutive patients who underwent PM-FBEVAR between September 2015 and December 2022 was performed. Patients with a single aortic component were excluded. The remaining patients were divided into single- or multimanufacturer groups. Patient demographics, aneurysm extent, and operative details were compared. The primary outcome was type IIIA endoleak. The secondary outcomes included reintervention for type IIIA endoleak, major adverse events, and mortality. These outcomes were compared out to 2 years. Freedom from type IIIA endoleak-related reintervention was estimated using the Kaplan-Meier analysis and compared between the groups using a log-rank test. Data from this cohort include those reported to the Food and Drug Administration in the physician-sponsored investigational device exemption application, and those enrolled in the physician-sponsored investigational device exemption (FDA#: G200159, NCI#:APP-20-04282). Of 232 patients included in this study, 44 patients received a single-manufacturer and 188 patients received multimanufacturer aortic components. Baseline demographics and aneurysm extent were similar between the groups. The majority of concomitant iliac aneurysms repaired with Iliac Branch Endoprosthesis were in the multimanufacturer group (24 of 25). Procedure time, contrast usage, fluoroscopy time, estimated blood loss, and transfusion were significantly lower for the multimanufacturer group (Table). The overall 30-day mortality (2.3% single vs 3.2% multimanufacturer, P = .99) and major adverse events (20.5% vs 20.2%, P = .97) were similar between the groups. At 2-year follow-up, type IIIA endoleak occurred in 3 (6.8%) in the single- and 4 patients (2.1%) in the multimanufacturer groups (P = .128). These endoleaks were repaired in 2 of 3 and 4 of 4 patients in each group (P = .319) (Fig). Two-year mortality was similar between the groups (15.9% vs 13.3%, P = .651). Aortic endografts from multiple manufacturers can be used to facilitate PM-FBEVAR without a significant increase in type IIIA endoleaks, major adverse events, and reinterventions at 2 years. Continued follow-up is planned to assess long-term durability.TableCharacteristics, operative metrics, and outcomes of single vs multimanufacturerTotalSingle manufacturerMultimanufacturerP value23244188Aneurysm characteristics, No. (%) Presentation.113Asymptomatic167 (72.3)27 (61.4)140 (74.9)Symptomatic59 (25.5)15 (34.1)44 (23.5)Ruptured5 (2.2)2 (4.5)3 (1.6) Anatomical classification.160Juxtarenal19 (8.2)3 (6.8)16 (8.5)Pararenal/paravisceral76 (32.8)9 (20.5)67 (35.6)Pseudoaneurysm2 (0.9)0 (0)2 (1.1)TAAA135 (58.2)32 (72.7)103 (54.8)TAAA extent.463Extent I20 (14.8)4 (12.5)16 (15.5)Extent II54 (40.0)11 (34.4)43 (41.7)Extent III23 (17.0)6 (18.8)17 (16.5)Extent IV35 (25.9)9 (28.1)26 (25.2)Extent V3 (2.2)2 (6.3)1 (1.0) Iliac aneurysms requiring IBE25 (10.8)1 (2.3)24 (12.8).055 Aneurysm max diameter68.2 (16.7)66.5 (12.0)68.6 (17.6).336Intraoperative metrics Procedure time, minutes287.9 ± 108.7329.1 ± 115.6278.3 ±105.0.005 Iodinated contrast, cc121.6 ± 58.3154.6 ± 72.9113.9 ± 51.5<.001 Fluoroscopy time, minutes63.9 ± 33.579.5 ± 34.660.3 ± 32.3<.001 Estimated blood loss, cc [median, IQR]150 [262.5]400 [487.5]100 [250]<.00130-day outcomes, No. (%) Mortality7 (3.0)1 (2.3)6 (3.2)1.000 Major adverse events47 (20.3)9 (20.5)38 (20.2).9712-year outcomes, No. (%) All-cause mortality32 (13.8)7 (15.9)25 (13.3).651 Type IIIA endoleak7 (3.0)3 (6.8)4 (2.1).128IBE, Iliac Branch Endoprosthesis; IQR, interquartile range; TAAA, thoracoabdominal aortic aneurysm. Open table in a new tab

Persistent Thrombocytopenia Indicates Endoleak After Complex Endovascular Aneurysm Repair

High-pressure endoleaks (types I or III) after fenestrated-branched endovascular aneurysm repair (F-BEVAR) pose an ongoing risk of rupture. Early identification of such endoleaks may facilitate appropriate reintervention and mitigate that risk. The purpose of this study was to determine if persistent thrombocytopenia after F-BEVAR correlates with the presence of a high-pressure endoleak in the early postoperative period. Sequential patients enrolled in a physician-sponsored investigational device exemption study of physician modified and Cook manufactured F-BEVAR endografts were evaluated. Patients with type I endoleak or type III endoleak identified on computed tomography imaging within the first 6 months of follow-up were categorized as high-pressure endoleaks; any type II endoleaks were classified as low-pressure endoleaks. Univariable and multivariable analysis was performed to assess if thrombocytopenia was associated with the presence of endoleaks. We treated 185 patients. Twenty-six patients (14%) developed a high-pressure endoleak and 30 (16%) developed a low-pressure endoleak (Table I). Age, gender, race, indications for the procedure, and preoperative medications did not significantly differ between the endoleak groups. To maximize sensitivity and clinical utility, we selected a cut point of daily average platelet count of <100,000/μL (Table II). The proportion of high-pressure endoleak patients with platelet counts of <100,000/μL was significantly greater compared to patients with low-pressure and no endoleaks on postoperative day (POD) 1 through 4 (POD 4: high-pressure 42%, low-pressure 27%, no endoleak 10%; P ≤ .001). After adjusting for demographics and comorbidities, patients with high-pressure endoleak were over 12-times more likely to have a platelet count of <100,000/μL on POD 4 compared to patients with no endoleak (odds ratio, 12.3; 95% confidence interval, 3.5-43.0). F-BEVAR patients who developed high- or low-pressure endoleak were significantly more thrombocytopenic in the postoperative period. Consideration should be made to perform computed tomography imaging in patients with platelet counts of <100,000/μL persisting at POD 4 after F-BEVAR as these patients have a 35% chance of having a high-pressure endoleak requiring reintervention.Table IProportion of patients with platelet count under 100,000/μL at preoperative (day 0), and postoperative days (POD) 1-7 after F-BEVAR among the type I, II, and III endoleak and no endoleak groupsDay 0Day 1Day 2Day 3Day 4Day 5Day 6Day 7No endoleak (n = 125)12 (10)17 (14)27 (22)28 (22)13 (10)11 (9)4 (3)4 (3)T1E/T3E (n = 26)7 (27)12 (46)15 (58)12 (46)11 (42)3 (12)1 (4)1 (4)T2E (n = 30)5 (17)10 (33)11 (37)13 (43)8 (27)5 (17)3 (10)1 (3)P value.06<.001.001.02<.001.8.6a1.0aT1EL/T3EL, Type I endoleak/type III endoleak; T2EL, type II endoleak.Data presented as number (%).aFisher's exact was used. Open table in a new tab Table IIComparison of the test characteristics of a cutpoint of <100,000/μL at different postoperative days (POD) for predicting the presence of a high-pressure endoleakSensitivity (95% CI)Specificity (95% CI)PPV (95% CI)NPV (95% CI)ROC area (95% CI)Average platelets <100,000/μL on POD 30.46 (0.29-0.66)0.77 (0.70-0.84)0.30 (0.18-0.46)0.87 (0.80-0.92)0.61 (0.51-0.72.)Average platelets <100,000/μL on POD 40.42 (0.26-0.63)0.89 (0.83-0.94)0.45 (0.29-0.67)0.88 (0.82-0.93)0.66 (0.55-0.76)Average platelets <100,000/μL on POD 3 or 40.50 (0.33-0.70)0.76 (0.68-0.83)0.31 (0.19-0.47)0.87 (0.80-0.93)0.62 (0.52-0.73)95% CI, 95% Confidence interval; NPV, negative predictive value; PPV, positive predictive value; ROC, receiver operating characteristic. Open table in a new tab

Gore thoracoabdominal branched endoprosthesis: early result and impressions.

The remarkable advances in technology and devices in the last two decades have made possible the endovascular repair of complex abdominal (cAAA) and thoracoabdominal (TAAA) aortic aneurysms with challenging anatomy. To date, despite the creation of multiple fenestrated/branched endografts intended to treat these difficult cases, in the USA, many of them remain available only under physician sponsored investigational device exemption (PSIDE) protocols in few institutions. The Gore Thoracoabdominal Branched Endoprosthesis (TAMBE; W.L. Gore & Associates, Flagstaff, AZ, USA) investigational device is a four-branched off-the-shelf (OTS) endograft that concluded an early feasibility study in 2016 and is currently finalizing a pivotal trial in pursuit of approval from the Food and Drug Administration. This article discusses the TAMBE early feasibility multicenter study results, the most relevant features of this device, its anatomical feasibility, and the impressions about this endograft as an OTS option for the treatment of CAAA and TAAA.