ASCT2-Targeting Antibody-Drug Conjugate MEDI7247 in Adult Patients with Relapsed/Refractory Hematological Malignancies: A First-in-Human, Phase 1 Study.

BACKGROUND: MEDI7247 is a first-in-class antibody-drug conjugate (ADC) consisting of an anti-sodium-dependent alanine-serine-cysteine transporter 2 antibody-conjugated to a pyrrolobenzodiazepine dimer. OBJECTIVE: This first-in-human phase 1 trial evaluated MEDI7247 in patients with hematological malignancies. PATIENTS AND METHODS: Adults with acute myeloid leukemia (AML), multiple myeloma (MM), or diffuse large B-cell lymphoma (DLBCL) relapsed or refractory (R/R) to standard therapies, or for whom no standard therapy exists, were eligible. Primary endpoints were safety and determination of the maximum tolerated dose (MTD). Secondary endpoints included assessments of antitumor activity, pharmacokinetics (PK), and immunogenicity. RESULTS: As of 26 March 2020, 67 patients were treated (AML: n = 27; MM: n = 18; DLBCL: n = 22). The most common MEDI7247-related adverse events (AEs) were thrombocytopenia (41.8%), neutropenia (35.8%), and anemia (28.4%). The most common treatment-related grade 3/4 AEs were thrombocytopenia (38.8%), neutropenia (34.3%), and anemia (22.4%). Anticancer activity (number of responders/total patients evaluated) was observed in 11/67 (16.4%) patients. No correlation was observed between ASCT2 expression and clinical response. Between-patient variability of systemic exposure of MEDI7247 ADC and total antibody were high (AUCinf geometric CV%: 62.3-134.2, and 74.8-126.1, respectively). SG3199 (PBD dimer) plasma concentrations were below the limit of quantification for all patients after Study Day 8. Anti-drug antibody (ADA) prevalence was 7.7%, ADA incidence was 1.9%, and persistent-positive ADA was 5.8%. CONCLUSIONS: Thrombocytopenia and neutropenia limited repeat dosing. Although limited clinical activity was detected, the dose-escalation phase was stopped early without establishing an MTD. The study was registered with ClinicalTrials.gov (NCT03106428).

Navigating the Healthcare Conundrum: Leadership Perspective from a Premier Healthcare Organization in Loma Linda's Blue Zone.

Navigating the healthcare conundrum in the Blue Zone of Loma Linda, California, requires understanding the unique factors that make this region stand out in terms of health and longevity. But more important is understanding the healthcare system sustaining the Blue Zone in Loma Linda, California. In an era marked by soaring healthcare costs and diminishing reimbursement rates, hospitals and physicians face an unprecedented challenge: providing excellent patient care while maintaining financial sustainability. This leadership perspective publication paper delves into the multifaceted struggles encountered by healthcare and hospital leaders, exploring the root causes, implications, and potential solutions for this complex issue. As we examine the evolving healthcare landscape, we aim to shed light on the critical need for innovative approaches to sustain the future of healthcare excellence in one of the five original Blue Zones.

Surgeons of the Future: A Novel Screening Tool for High-School Students.

INTRODUCTION: Given a looming shortage of surgeons and currently inadequate pipelines into our specialty for under-represented groups, there is an urgent need to identify and foster interest in young individuals who may have great potential as future surgeons. We aimed to explore the utility and feasibility of a novel survey instrument to identify high-school students well suited for careers in surgery based on personality profiling and grit. METHODS: An electronic screening tool was developed, combining components of the Myers-Briggs personality profile, the Big-Five Inventory 10, and the grit scale. This brief questionnaire was electronically distributed to surgeons and students across two academic institutions and three high schools (one private and two public). Wilcoxon rank-sum test and Chi-squared/Fisher's exact test were performed to evaluate variations between groups. RESULTS: Surgeons (n = 96) displayed mean Grit score of 4.03 (range: 3.08-4.92; standard deviation: 0.43), while high-schoolers' (n = 61) mean score was 3.38 (range: 2.08-4.58; standard deviation: 0.62) (P < 0.0001). Surgeons showed Myers-Brigg Type Indicator trait-dominance toward extroversion, intuition, thinking, and judging, while students displayed greater breadth of traits. Students were much less likely to show dominance in introversion versus extroversion (P < 0.0001) as well as perceiving versus judging (P < 0.0001). Big-Five Inventory 10 traits of neuroticism and conscientiousness were more prevalent among surgeons (P < 0.0001 for both). CONCLUSIONS: Importantly, there exists a subgroup of high-school students with personality and grit similar to those of surgeons. Moreover, we have demonstrated the feasibility of using this novel screening tool for future studies aimed to create pipelines for early exposure opportunities and mentorship.

Hot topics in interventional cardiology: Proceedings from the society for cardiovascular angiography and interventions (SCAI) 2021 think tank.

The Society for Cardiovascular Angiography and Interventions (SCAI) Think Tank is a collaborative venture that brings together interventional cardiologists, administrative partners, and select members of the cardiovascular industry community annually for high-level field-wide discussions. The 2021 Think Tank was organized into four parallel sessions reflective of the field of interventional cardiology: (a) coronary intervention, (b) endovascular medicine, (c) structural heart disease, and (d) congenital heart disease. Each session was moderated by a senior content expert and co-moderated by a member of SCAI's Emerging Leader Mentorship program. This document presents the proceedings to the wider cardiovascular community in order to enhance participation in this discussion, create additional dialog from a broader base, and thereby aid SCAI, the industry community and external stakeholders in developing specific action items to move these areas forward.

Hot topics in interventional cardiology: Proceedings from the society for cardiovascular angiography and interventions 2020 think tank.

The society for cardiovascular angiography and interventions (SCAI) think tank is a collaborative venture that brings together interventional cardiologists, administrative partners, and select members of the cardiovascular industry community for high-level field-wide discussions. The 2020 think tank was organized into four parallel sessions reflective of the field of interventional cardiology: (a) coronary intervention, (b) endovascular medicine, (c) structural heart disease, and (d) congenital heart disease (CHD). Each session was moderated by a senior content expert and co-moderated by a member of SCAI's emerging leader mentorship program. This document presents the proceedings to the wider cardiovascular community in order to enhance participation in this discussion, create additional dialogue from a broader base, and thereby aid SCAI and the industry community in developing specific action items to move these areas forward.

SCAI position statement on the performance of percutaneous coronary intervention in ambulatory surgical centers.

The Centers for Medicare & Medicaid Services (CMS) began reimbursement for percutaneous coronary intervention (PCI) performed in ambulatory surgical centers (ASC) in January 2020. The ability to perform PCI in an ASC has been made possible due to the outcomes data from observational studies and randomized controlled trials supporting same day discharge (SDD) after PCI. In appropriately selected patients for outpatient PCI, clinical outcomes for SDD or routine overnight observation are comparable without any difference in short-term or long-term adverse events. Furthermore, a potential for lower cost of care without a compromise in clinical outcomes exists. These studies provide the framework and justification for performing PCI in an ASC. The Society for Cardiovascular Angiography and Interventions (SCAI) supported this coverage decision provided the quality and safety standards for PCI in an ASC were equivalent to the hospital setting. The current position paper is written to provide guidance for starting a PCI program in an ASC with an emphasis on maintaining quality standards. Regulatory requirements and appropriate standards for the facility, staff and physicians are delineated. The consensus document identified appropriate patients for consideration of PCI in an ASC. The key components of an ongoing quality assurance program are defined and the ethical issues relevant to PCI in an ASC are reviewed.

Effects of zamicastat treatment in a genetic model of salt-sensitive hypertension and heart failure.

Hyperactivity of sympathetic nervous system plays an important role in the development and progression of cardiovascular diseases. An approach to mitigate the enhanced sympathetic nervous system drive is restricting the biosynthesis of noradrenaline via inhibition of the enzyme dopamine ß-hydroxylase (DßH), that catalyzes the hydroxylation of dopamine to noradrenaline in sympathetic nerves. The aim of the present study was to evaluate the effects of zamicastat, a novel DßH inhibitor that decreases noradrenaline and increases dopamine levels in peripheral sympathetically innervated tissues, on the hemodynamic and cardiometabolic parameters in salt-induced hypertension and heart failure in the Dahl salt-sensitive (SS) rat. Zamicastat (10, 30 and 100 mg/kg body weight) was tested acutely against salt-induced hypertension in the Dahl SS rat. Chronic zamicastat treatment (30 mg/kg/day) was evaluated against salt-induced cardiac hypertrophy and biomarkers of cardiometabolic risk and inflammation in Dahl SS rats and upon the survival rate in aged Dahl SS rats fed a high-salt diet. The reduction in the sympathetic tone attained with zamicastat shaped a dose- and time-dependent effect on blood pressure. Prolonged treatment with zamicastat ameliorated end-organ damage, metabolic syndrome and inflammation hallmarks in hypertensive Dahl SS rats. Survival rate of Dahl SS rats fed a high-salt diet demonstrated that zamicastat increased median survival of Dahl SS rats fed a high-salt diet. The use of DßH inhibitors, like zamicastat, is a promising approach to treat hypertension, heart failure and cardiovascular diseases where a reduction in the sympathetic tone has beneficial effects.

Achieving timely percutaneous reperfusion for rural ST-elevation myocardial infarction patients by direct transport to an urban PCI-hospital.

BACKGROUNDS: ST-elevation myocardial infarction (STEMI) guidelines recommend reperfusion by primary percutaneous coronary intervention (PCI) ≤ 90 min from time of first medical contact (FMC). This strategy is challenging in rural areas lacking a nearby PCI-capable hospital. Recommended reperfusion times can be achieved for STEMI patients presenting in rural areas without a nearby PCI-capable hospital by ground transportation to a central PCI-capable hospital by use of protocol-driven emergency medical service (EMS) STEMI field triage protocol. METHODS: Sixty STEMI patients directly transported by EMS from three rural counties (Nassau, Camden and Charlton Counties) within a 50-mile radius of University of Florida Health-Jacksonville (UFHJ) from 01/01/2009 to 12/31/2013 were identified from its PCI registry. The STEMI field triage protocol incorporated three elements: (1) a cooperative agreement between each of the rural emergency medical service (EMS) agency and UFHJ; (2) performance of a pre-hospital ECG to facilitate STEMI identification and laboratory activation; and (3) direct transfer by ground transportation to the UFHJ cardiac catheterization laboratory. FMC-to-device (FMC2D), door-to-device (D2D), and transit times, the day of week, time of day, and EMS shift times were recorded, and odds ratio (OR) of achieving FMC2D times was calculated. RESULTS: FMC2D times were shorter for in-state STEMIs (81 ± 17 vs. 87 ± 19 min), but D2D times were similar (37 ± 18 vs. 39 ± 21 min). FMC2D ≤ 90 min were achieved in 82.7% in-state STEMIs compared to 52.2% for out-of-state STEMIs (OR = 4.4, 95% CI: 1.24-15.57; P = 0.018). FMC2D times were homogenous after adjusting for weekday vs. weekend, EMS shift times. Nine patients did not meet FMC2D ≤ 90 min. Six were within 10 min of target; all patient achieved FMC2D ≤ 120 min. CONCLUSIONS: Guideline-compliant FMC2D ≤ 90 min is achievable for rural STEMI patients within a 50 mile radius of a PCI-capable hospital by use of protocol-driven EMS ground transportation. As all patients achieved a FMC2D time ≤ 120 min, bypass of non-PCI capable hospitals may be reasonable in this situation.

Sustained high blood pressure reduction with etamicastat, a peripheral selective dopamine ß-hydroxylase inhibitor.

The aim of the present study was to evaluate the influence of chronic inhibition of dopamine ß-hydroxylase by etamicastat on the development of hypertension in the spontaneously hypertensive rat (SHR) and the sustainability of effects on the systolic and diastolic blood pressure in the SHR and the normotensive Wistar-Kyoto rat (WKY). WKY and SHR received etamicastat (10 mg/kg/d) from 5 weeks of age for 35 weeks in drinking water, and cardiovascular assessments were performed on a weekly basis. Etamicastat reduced systolic and diastolic blood pressure when SHRs reached the age of 16 weeks with mean decreases of 37 and 32 mm Hg, respectively, for the subsequent for 24 weeks of treatment, but did not prevent the increase in blood pressure (BP) aged between 5 and 11 week. The BP lowering effect of etamicastat in SHR was reversible on discontinuation and quickly resumed after reinstatement of therapy and was not accompanied by changes in heart rate. Etamicastat affected neither BP nor heart rate in WKY during 36 weeks of treatment. Etamicastat reduced urinary excretion of norepinephrine to a similar extent in WKY and SHR, accompanied by significant increases in urinary dopamine in SHR. Chronic administration of etamicastat did not adversely affected development of animals. Chronic dopamine ß-hydroxylase inhibition with etamicastat effectively decreases BP, although does not prevent the development of hypertension in the SHR.

Eslicarbazepine acetate for the treatment of focal epilepsy: an update on its proposed mechanisms of action.

Eslicarbazepine acetate (ESL) is a once daily antiepileptic drug (AED) approved by the European Medicines Agency (EMA), the Food and Drug Administration (FDA) and Health Canada as an adjunctive therapy in adults with partial-onset seizures (POS). In humans and in relevant animal laboratory species, ESL undergoes extensive first pass hydrolysis to its major active metabolite eslicarbazepine that represents ∼95% of circulating active moieties. ESL and eslicarbazepine showed anticonvulsant activity in animal models. ESL may not only suppress seizure activity but may also inhibit the generation of a hyperexcitable network. Data reviewed here suggest that ESL and eslicarbazepine demonstrated the following in animal models: (1) the selectivity of interaction with the inactive state of the voltage-gated sodium channel (VGSC), (2) reduction in VGSC availability through enhancement of slow inactivation, instead of alteration of fast inactivation of VGSC, (3) the failure to cause a paradoxical upregulation of persistent Na(+) current (I NaP), and (4) the reduction in firing frequencies of excitatory neurons in dissociated hippocampal cells from patients with epilepsy who were pharmacoresistant to carbamazepine (CBZ). In addition, eslicarbazepine effectively inhibited high- and low-affinity hCaV3.2 inward currents with greater affinity than CBZ. These preclinical findings may suggest the potential for antiepileptogenic effects; furthermore, the lack of effect upon KV7.2 outward currents may translate into a reduced potential for eslicarbazepine to facilitate repetitive firing.

Role of P-glycoprotein and permeability upon the brain distribution and pharmacodynamics of etamicastat: a comparison with nepicastat.

1. This study explores the impact of permeability and P-glycoprotein (P-gp) efflux, upon brain exposure to etamicastat, a new dopamine-ß-hydroxylase (DBH) inhibitor and consequently brain levels of catecholamines. 2. Brain exposure to etamicastat (10 mg/kg), following intravenous administration to mice, was residual and upon oral administration of the same dose no compound was detected, concurring with the absence of effects upon brain catecholamines. The intravenous co-administration of elacridar (1.0 mg/kg), a known P-gp/BCRP dual modulator, significantly increased brain etamicastat exposure, but the levels attained were very low when compared to those of nepicastat, a centrally active DBH inhibitor. 3. In vitro permeability studies from apical-to-basal direction conducted in Caco-2 cells and MDCK-II cells showed that etamicastat apparent permeability was 1.2 × 10(-5) and 1.1 × 10(-6 )cm/s, respectively, 5- and 50-fold lower as compared to nepicastat. The secretory efflux ratio in MDCK-II cells overexpressing human P-gp showed an efflux ratio greater than 2, for both compounds, which was significantly decreased by elacridar. Despite its lower bioavailability and higher clearance, as compared to nepicastat, etamicastat showed preferential distribution to peripheral tissues and high plasma free fraction (15.5%), which may explain its effects upon peripheral DBH and catecholamine levels. 4. Though P-gp-mediated efflux may contribute to the limited brain penetration of etamicastat, the low permeability along with the pharmacokinetic properties of etamicastat may be perceived as the main contributors for its peripheral selectivity, which is advantageous for a cardiovascular drug candidate.

Characterization of the interaction of the novel antihypertensive etamicastat with human dopamine-ß-hydroxylase: comparison with nepicastat.

The interaction of etamicastat, a novel peripherally acting dopamine-ß-hydroxylase (DBH) inhibitor, with the enzyme was studied using a classical kinetic approach and the pharmacodynamics effect of the compound upon administration to rats was also evaluated. SK-N-SH cell homogenates convert tyramine into octopamine with a Km value of 9 mM, and a Vmax of 1747 nmol/mg protein/h. The K(m) value for ascorbate was 3 mM. The inhibition of DBH by etamicastat and nepicastat, a known centrally acting DBH inhibitor, with IC50 values of 107 and 40 nM, respectively, was fully reversed by dilution. Non-linear fitting of the velocities, determined at various concentrations of substrate (tyramine) and co-substrate (ascorbic acid), and of etamicastat and nepicastat, indicated that the inhibition of DBH by both compounds follows a mixed-model inhibition mechanism, approaching competitive behavior with regards to the substrate tyramine, with K(i) values of 34 and 11 nM, respectively. Relatively to ascorbate, both compounds followed a mixed-model inhibition mechanism, approaching uncompetitive behavior. Oral administration of both compounds (at 30 mg/kg) inhibited adrenal DBH activity over time and significantly decreased noradrenaline levels in the heart. Nepicastat also decreased noradrenaline levels in the parietal cortex, but not etamicastat. Both compounds significantly decreased systolic and diastolic blood pressure in spontaneously hypertensive rats. In conclusion, etamicastat and nepicastat behave as multisubstrate DBH inhibitors, binding reversibly and preferentially to the reduced form of the enzyme, and simultaneously at the substrate and oxygen binding sites. Etamicastat, in contrast to nepicastat, offers the advantage of peripheral selectivity without central effects.

Effects of eslicarbazepine acetate on acute and chronic latrunculin A-induced seizures and extracellular amino acid levels in the mouse hippocampus.

BACKGROUND: Latrunculin A microperfusion of the hippocampus induces acute epileptic seizures and long-term biochemical changes leading to spontaneous seizures. This study tested the effect of eslicarbazepine acetate (ESL), a novel antiepileptic drug, on latrunculin A-induced acute and chronic seizures, and changes in brain amino acid extracellular levels. Hippocampi of Swiss mice were continuously perfused with a latrunculin A solution (4 µM, 1 µl/min, 7 h/day) with continuous EEG and videotape recording for 3 consecutive days. Microdialysate samples were analyzed by HPLC and fluorescence detection of taurine, glycine, aspartate, glutamate and GABA. Thereafter, mice were continuously video monitored for two months to identify chronic spontaneous seizures or behavioral changes. Control EEG recordings (8 h) were performed in all animals at least once a week for a minimum of one month. RESULTS: Oral administration of ESL (100 mg/kg), previous to latrunculin A microperfusion, completely prevented acute latrunculin A-induced seizures as well as chronic seizures and all EEG chronic signs of paroxysmal activity. Hippocampal extracellular levels of taurine, glycine and aspartate were significantly increased during latrunculin A microperfusion, while GABA and glutamate levels remained unchanged. ESL reversed the increases in extracellular taurine, glycine and aspartate concentrations to basal levels and significantly reduced glutamate levels. Plasma and brain bioanalysis showed that ESL was completely metabolized within 1 h after administration to mainly eslicarbazepine, its major active metabolite. CONCLUSION: ESL treatment prevented acute latrunculin A-induced seizures as well as chronic seizures and all EEG chronic signs of paroxysmal activity, supporting a possible anti-epileptogenic effect of ESL in mice.

Etamicastat, a new dopamine-ß-hydroxylase inhibitor, pharmacodynamics and metabolism in rat.

Despite the importance of sympathetic nervous system in pathophysiological mechanisms of cardiac heart failure and essential hypertension, therapy specifically targeting the sympathetic nervous system is currently underutilized. Etamicastat is a novel dopamine-ß-hydroxylase (DBH) inhibitor that is oxidized into BIA 5-965 and deaminated followed by oxidation to BIA 5-998, which represents 13% of total etamicastat and quantified metabolites. However, the primary metabolic pathway of etamicastat in rats was found to be the N-acetylation (BIA 5-961), which represents 44% of total etamicastat and quantified metabolites. Trace amounts of BIA 5-961 de-sulfated and S-glucuronide were also detected. All the main metabolites of etamicastat inhibited DBH with IC50 values of 306 (228, 409), 629 (534, 741), 427 (350, 522) nM for BIA 5-965, BIA 5-998 and BIA 5-961, respectively. However, only etamicastat (IC50 of 107 (94; 121) nM) was able to reduce catecholamine levels in sympathetic nervous system innervated peripheral tissues, without effect upon brain catecholamines. Quantitative whole body autoradiography revealed a limited transfer of etamicastat related radioactivity to brain tissues and the mean recovery of radioactivity was ~90% of the administered radioactive dose, eliminated primarily via renal excretion over 5 days. The absolute oral bioavailability of etamicastat was 64% of the administered dose. In conclusion, etamicastat is a peripheral selective DBH inhibitor mainly N-acetylated in the aminoethyl moiety and excreted in urine. Etamicastat main metabolites inhibit DBH, but only etamicastat demonstrated unequivocal pharmacological effects as a DBH inhibitor with impact upon the activity of the sympathetic nervous system under in vivo conditions.

Effect of opicapone and entacapone upon levodopa pharmacokinetics during three daily levodopa administrations.

BACKGROUND AND OBJECTIVES: Opicapone is a novel third generation catechol-O-methyltransferase (COMT) inhibitor. The purpose of this study was to compare the levodopa pharmacokinetic profile throughout a day driven by the COMT inhibition either following repeated doses of opicapone or concomitant administration with entacapone. METHODS: A randomized, double-blind, gender-balanced, parallel-group study was performed in 4 groups of 20 healthy subjects each. Four subjects in each group received placebo during the entire study. Sixteen subjects in one group received placebo once daily for 11 days and on day 12, 200 mg entacapone concomitantly with each levodopa/carbidopa dose (three times separated by a 5-h interval). Sixteen subjects in each of the remaining three groups received respectively 25, 50, and 75 mg opicapone once daily for 11 days and on day 12, placebo concomitantly with each levodopa/carbidopa dose. RESULTS: Levodopa minimum plasma concentration (Cmin) for each levodopa/carbidopa dose and for the mean of all levodopa/carbidopa doses increased substantially with all active treatments (entacapone and opicapone) when compared to the control group (placebo), with values ranging from 1.7-fold (200 mg entacapone) to 3.3-fold (75 mg opicapone). No statistical difference was found for levodopa peak of systemic exposure (as assessed by maximum observed plasma concentration (Cmax)) between all active treatments and placebo. A significant increase in the levodopa extent of systemic exposure (as assessed by concentration-time curve (AUC)) occurred with all opicapone treatments in relation to placebo. No statistical difference was found for levodopa AUC when entacapone was compared to placebo. When compared to entacapone, both 50 and 75 mg opicapone presented a significant increase for the levodopa AUC. All active treatments significantly inhibited both peak (as assessed by Emax) and extent (as assessed by effect-time curve (AUEC)) of the COMT activity in relation to placebo. When compared to entacapone, all opicapone treatments significantly decreased the extent (AUEC) of the COMT activity due to a long-lasting and sustained effect. The tolerability profile was favorable for all active treatments. CONCLUSION: Opicapone, a novel third generation COMT inhibitor, when compared to entacapone, provides a superior response upon the bioavailability of levodopa associated to more pronounced, long-lasting, and sustained COMT inhibition. The tolerability profile was favorable. On the basis of the results presented in this study and along with the earlier pharmacology studies, it is anticipated that opicapone adjunct therapy at the dosages of 25 and 50 mg will provide an enhancement in levodopa availability that will translate into clinical benefit for Parkinson's disease patients.

Operator radiation exposure and physical discomfort during a right versus left radial approach for coronary interventions: a randomized evaluation.

OBJECTIVES: This study sought to assess radiation exposure and operator discomfort when using left radial approach (LRA) versus right radial approach (RRA) for coronary diagnostic and percutaneous interventions. BACKGROUND: The transradial approach is increasingly being adopted as the preferred vascular access for coronary interventions. Currently, most are performed using an RRA. This is in part due to the perceived increased operator physical discomforts as well increased radiation exposure with an LRA. METHODS: One hundred patients were randomized to an LRA or RRA. Each operator (n = 5) had an independent randomization process, and patients were stratified according to obesity status. Operator radiation was measured using separate sets of radiation dosimeter badges placed externally on the head and thyroid and internally on the sternum. Operator physical discomfort was surveyed at 2 time points: during vascular access and at the end of the procedure. Moderate to severe physical discomfort was defined as a score of >4. RESULTS: There were no significant differences in baseline and procedural variables between groups. There was a significant increase in external radiation exposure using the RRA versus LRA (head: median: 6.12 [interquartile range (IQR): 2.6 to 16.6] mRems vs. median: 12.0 [IQR: 6.4 to 22.0] mRems, p = 0.02; thyroid: median: 10.10 [IQR: 4.3 to 25] mRems vs. median: 18.70 [IQR: 11.0 to 38] mRems, p = 0.001). More discomfort was reported with the LRA during access (LRA: 22% vs. RRA: 4%; p = 0.017), but not during the procedure (LRA: 10.0% vs. RRA: 4.0%, p = 0.43). This difference was almost entirely noted in obese patients (LRA: 30.0% vs. RRA: 3.7%, p = 0.005). CONCLUSIONS: LRA is as effective as RRA, showing a safer profile with decreased radiation exposure to the operator, at the expense of more operator discomfort only during vascular access and limited to obese patients.