Department Of Veterans Affairs Research Articles

First Decade of Supportive Services for Veteran Families Program and Homelessness, 2012-2022.

As homelessness remains an urgent public health crisis in the United States, specific programs in the US Department of Veterans Affairs (VA) system may serve as a roadmap for addressing it. We examine lessons learned from the first decade (2012-2022) of the Supportive Services for Veteran Families (SSVF) program, a cornerstone in the VA continuum of homeless services aimed at both preventing homelessness among those at risk and providing rapid rehousing for veterans and their families who are currently experiencing homelessness. Drawing on information from annual reports and other relevant literature, we have identified 3 themes of SSVF that emerged as features to comprehensively deliver support for homeless veterans and their families: (1) responsiveness and flexibility, (2) coordination and integration, and (3) social resource engagement. Using these strategies, SSVF reached nearly three quarters of a million veterans and their families in its first decade, thereby becoming one of the VA's most substantial programmatic efforts designed to address homelessness. We discuss how each feature might apply to addressing homelessness in the general population as well as future research directions. (Am J Public Health. 2024;114(6):610-618. https://doi.org/10.2105/AJPH.2024.307625).

Suicide Prevention Programming: Comparing Four Prominent Frameworks.

Suicide is a significant public health concern. About 48,000 individuals died by suicide in 2021 in the United States, and approximately one in 100 deaths globally are due to suicide. Continuing efforts in program development and evaluation are vital to preventing suicide. Multiple frameworks have been developed to reduce suicide rates, but they have not been compared to assess their comprehensiveness, nor have their components been classified. In 2019, the authors conducted a narrative review of the literature and identified four major frameworks for suicide prevention: the U.S. Department of Veterans Affairs (VA) Suicide Prevention Program, the Defense Suicide Prevention Program of the U.S. Department of Defense, Zero Suicide in Health and Behavioral Health Care, and the technical package developed by the Centers for Disease Control and Prevention. Program components for these frameworks were identified and classified by using two prevention strategy classification systems: the National Academy of Medicine's (NAM's) continuum-of-care model and the Substance Abuse and Mental Health Services Administration's (SAMHSA's) prevention model. The cross-program comparison revealed that no single program included all components of suicide prevention programs. However, the VA program was the most comprehensive in terms of the number of components and their spread across prevention strategy classifications. The programs used few components categorized under NAM's promotion or selective prevention strategy classifications. The SAMHSA prevention strategy classifications of information dissemination, community-based processes, and positive alternatives were also used infrequently. Organizations, health care systems, and policy makers may use these findings as they develop, improve, and implement suicide prevention programs.

Association of Pharmacogenomic Phenotypes in CYP2D6, CYP2C9, CYP2C19, and CYP3A5 on Polypharmacy in Veterans.

The Department of Veterans Affairs (VA) utilizes a pharmacogenomic (PGx) program that analyzes specific "pharmacogenes." This study evaluates the effect that pharmacogenes may have on prevalence of polypharmacy. This retrospective cohort study included patients with VA prescriptions who underwent PGx testing. We quantified prescriptions active or recently expired at the time of PGx testing. We constructed two co-primary polypharmacy (≥10 medications) end points: (i) based on all medications and (ii) requiring that at least one medication was affected by a pharmacogene of interest. Pharmacogenes and actionable phenotypes of interest included poor and ultrarapid metabolizers for CYP2D6, CYP2C9, and CYP2C19 and intermediate and normal metabolizers for CYP3A5. Patients were classified as having 0, 1, and 2+ total phenotypes across all genes. Of the 15,144 patients screened, 13,116 met eligibility criteria. Across phenotype cohorts, there was no significant association with polypharmacy using all medications, number of total medications, or number of medications affected by phenotypes. However, there was a significant difference in patients with polypharmacy prescribed ≥1 medication impacted by PGx across phenotype groups: 2,514/4,949 (51%), 1,349/2,595 (52%), 204/350 (58%) (P = 0.03, OR 1.31, 95% CI 1.02-1.67). The median number of medications affected by PGx phenotypes with ≥1 PGx-impacted medication across phenotype groups was a median of 0 (IQR 0, 0), 0 (IQR 0, 0), and 1 (IQR 0, 1) (P < 0.001). In patients prescribed ≥1 medication impacted by PGx, those with more actionable pharmacogenomic phenotypes were more likely to meet polypharmacy criteria.

Irritable Bowel Syndrome in Veterans with Gulf War Illness Evaluated at VA's War-Related Illness and Injury Study Center.

Excess rates of Gulf War illness (GWI) and irritable bowel syndrome (IBS), two chronic multisymptom illnesses, have long been documented among nearly 700,000 veterans who served in the 1990-1991 Persian Gulf War. We sought to report the prevalence, characteristics, and association of GWI and IBS decades after the war in a clinical cohort of deployed Gulf War veterans (GWVs) who were evaluated at the Department of Veterans Affairs' War Related Illness and Injury Study Center (WRIISC) for unexplained chronic symptoms. We analyzed data gathered from clinical intake questionnaires of deployed GWVs who were evaluated at WRIISC clinics between 2008 and 2020. We applied Centers for Disease Control (CDC) criteria to determine the prevalence of severe GWI. IBS was identified using Rome IV diagnostic criteria (current IBS) and veterans' self-reported "history of physician-diagnosed IBS." We examined associations between IBS and GWI using bivariate analyses and multivariable logistic regression. Among the N = 578 GWVs evaluated by the WRIISC, severe GWI (71.8%), history of physician-diagnosed IBS (50.3%) and current IBS (42.2%) were all highly prevalent. Nearly half of GWVs with severe GWI met Rome criteria for IBS (45.8%), and over half reported a history of physician-diagnosed IBS (56.1%). In multivariable models, severe GWI was significantly associated both with current IBS (adjusted odds ratio (aOR): 1.68, 95% CI: 1.11, 2.54) and with veteran-reported history of physician-diagnosed IBS (aOR: 2.15, 95% CI: 1.43, 2.23). IBS with diarrhea (IBS-D) was the most common subtype among GWVs with current IBS (61.1%). However, IBS-mixed affected a significantly greater proportion of veterans with severe GWI, compared to veterans who did not have severe GWI (P = .03). More than 20 years after the Persian Gulf War, our findings indicate a high degree of comorbidity between severe GWI and IBS among deployed GWVs seeking care for unexplained illnesses. Our results suggest GWVs with GWI should be screened for IBS for which evidence-based treatments are available and could potentially reduce symptom burden. Conversely, symptoms of IBS should trigger additional evaluation for non-gastrointestinal symptoms in deployed Gulf War veterans to identify possible GWI and ensure a comprehensive approach to care.

Well-Being Domains in U.S. Military Veterans: Identifying Modifiable Factors to Promote Whole Health.

The U.S. Department of Veterans Affairs is actively transitioning away from a disease-centric model of healthcare to one that prioritizes disease prevention and the promotion of overall health and well-being. Described as Whole Health, this initiative aims to provide personalized, values-centered care that optimizes physical, behavioral, spiritual, and socioeconomic well-being. To inform this initiative, we analyzed cross-sectional data from a nationally representative sample of primarily older U.S. military veterans to estimate levels of well-being across these domains, and identify sociodemographic, military, and potentially modifiable health and psychosocial correlates of them. Results revealed that, overall, veterans reported high domain-specific well-being (average scores ranging from 6.7 to 8.3 out of 10), with the highest levels in the socioeconomic domain and lowest in the physical domain. Several modifiable factors, including purpose in life, resilience, and social support, were strongly associated with the examined well-being domains. Interventions targeting these constructs may help promote well-being among U.S. veterans.

Estimating the size and scope of the academic emergency physician workforce.

Academic emergency medicine (EM) is foundational to the EM specialty through the development of new knowledge and clinical training of resident physicians. Despite recent increased attention to the future of the EM workforce, no evaluations have specifically characterized the U.S. academic EM workforce. We sought to estimate the national proportion of emergency physicians (EPs) identified as academic and the proportion of emergency department (ED) visits that take place at academic sites. We performed a cross-sectional analysis of EPs and EDs using data from the American Hospital Association, the Centers for Medicare & Medicaid Services, and Doximity's Residency Navigator. EPs were identified as "academic" if they were affiliated with at least one facility determined to be academic, defined as EDs officially designated by the Accreditation Council for Graduate Medical Education (ACGME) as clinical training sites at accredited EM residency programs. Our primary outcomes were to estimate the national proportion of EPs identified as academic and the proportion of ED visits performed at academic sites. Our analytic sample included 26,937 EPs practicing clinically across 4920 EDs and providing care during 130,471,386 ED visits. Among EPs, 11,720 (43.5%) were identified as academic, and among EDs, 635 (12.9%) were identified as academic sites, including 585 adult/general sites, 45 pediatric-specific sites, and 10 sites affiliated with the Department of Veterans Affairs. In 2021, academic EDs provided care for 42,794,106 ED visits or 32.8% of all ED visits nationally. Approximately four in 10 EPs practice in at least one clinical training site affiliated with an ACGME-accredited EM residency program, and approximately one in three ED visits nationally occur in these academic EDs. We encourage further work using alternative definitions of an academic EPs and EDs, along with longitudinal research to identify trends in the workforce's composition.

Developing national cancer survivorship standards to inform quality of care in the United States using a consensus approach.

To develop United States (US) standards for survivorship care that informs (1) essential health system policy and process components and (2) evaluation of the quality of survivorship care. The National Cancer Institute and the Department of Veterans Affairs led a review to identify indicators of quality cancer survivorship care in the domains of health system policy, process, and evaluation/assessment. A series of three virtual consensus meetings with survivorship care and research experts and advocates was conducted to rate the importance of the indicators and refine the top indicators. The final set of standards was developed, including ten indicators in each domain. Prioritized items were survivor-focused, including processes to both assess and manage physical, psychological, and social issues, and evaluation of patient outcomes and experiences. Specific indicators focused on developing a business model for sustaining survivorship care and collecting relevant business metrics (e.g., healthcare utilization, downstream revenue) to show value of survivorship care to health systems. The National Standards for Cancer Survivorship Care can be used by health systems to guide development of new survivorship care programs or services or to assess alignment and enhance services in existing survivorship programs. Given the variety of settings providing care to survivors, it is necessary for health systems to adapt these standards based on factors including age-specific needs, cancer types, treatments received, and health system resources. With over 18 million cancer survivors in the United States, many of whom experience varied symptoms and unmet needs, it is essential for health systems to have a comprehensive strategy to provide ongoing care. The US National Standards for Survivorship Care should serve as a blueprint for what survivors and their families can anticipate after a cancer diagnosis to address their needs.

Serving Those Who Served: Enhancing Colorectal Surgery Care for Veterans

AbstractThe Department of Veterans Affairs (VA) is the largest provider of integrated health care services in the United States and its mission is to honor veterans by providing timely, effective, and high-quality health care that improves individuals' health and functionality. The VA provides comprehensive primary and specialty care, including colorectal surgery services, to eligible veterans who suffer from a disproportionately high burden of medical comorbidities and often belong to vulnerable populations, including individuals of low socioeconomic status, those who identify as lesbian, gay, bisexual, transgender, and questioning, racial minorities, and those suffering from severe mental health illness. There are many challenges to caring for a population of veterans with benign and malignant colorectal disease due to both patient and system level factors. Despite these challenges, the VA has demonstrated a commitment to ensuring culturally competent, equitable, and inclusive care and to conducting research that establishes evidence-based best practices in the management of colorectal diseases. These efforts have led to outcomes for patients undergoing care for colorectal diseases within the VA that are par with or better than civilian outcomes. The VA is uniquely positioned on a system level to provide nationwide efforts that improve care delivery and serve those who served.

Connecting unstably housed veterans living in rural areas to health care: Perspectives from Health Care Navigators.

To understand existing care practices and policies, and potential enhancements, to improve the effectiveness of the US Department of Veterans Affairs (VA) Supportive Services for Veteran Families (SSVF) Health Care Navigators (HCN) in linking Veterans experiencing housing instability in rural areas with health care services. We used primary data collected during semistructured interviews with HCNs (n = 21) serving rural areas across the United States during Spring 2022. We applied the Consolidated Framework for Implementation Research (CFIR) 2009 and the Social Ecological Model (SEM) to the collection and analysis of qualitative data to understand how HCNs administer services within SSVF and the larger community. We used rapid qualitative methods to summarize and analyze data. Templated matrix summaries identified facilitators and barriers to linking Veterans with health care services and policy and practice implications. Using CFIR 2009, we identified contextual factors affecting successful implementation of HCN services within SSVF; we offer a crosswalk between CFIR 2009 and the version updated in 2022. Framing facilitators and barriers within the SEM provided insight into whether implementation strategies should be addressed at a community, interpersonal, or intrapersonal level within the SEM. Facilitators included sufficient knowledge, training, and mentorship opportunities for HCNs and their capacity to collaborate within their organization and with other community-based organizations. Barriers included lack of local technology and housing resources, inadequate understanding of Veterans' service eligibilities and pathways to access those services, and deficient collaboration with the VA. Understanding facilitators and barriers experienced by HCN when linking unstably housed Veterans in rural areas with health care services can inform future strategies, including policy changes such as increased training to support HCNs' understanding of eligibility, benefits, and entitlements as well as improving communication and collaboration between VA and community partners.

Peer support during in vivo exposure homework increases likelihood of prolonged exposure therapy completion

ABSTRACT Exposure-based treatments such as prolonged exposure therapy (PE) are effective for veterans with PTSD. However, dropout rates as high as 50% are common. The Department of Veterans Affairs employs peers to increase mental health treatment engagement, however peers are not routinely used to help patients complete PE homework assignments. The present study included 109 veterans who decided to drop out from exposure-based treatment after completing seven or fewer sessions and used a randomized controlled design to compare PE treatment completion rates in response to 2 forms of peer support: (1) standard weekly telephone-based peer support vs. (2) peer-assisted in vivo exposure, wherein peers accompanied veterans (virtually or in person) during a limited number of in vivo exposure assignments. There were no differences between instrumental vs general peer support conditions as randomized. However, post hoc analyses indicated that 87% of those who completed at least one peer-assisted in vivo exposure completed treatment, compared to 56% of those not completing any peer-assisted in vivo exposure. The dose effect of peer-assisted in vivo exposure increased to 93% with 2 or more peer-assisted exposures, and 97% with 3 or more peer-assisted exposures. The present study suggests that augmenting PE with instrumental peer support during in vivo exposure homework may reduce dropout if completed. Future research should test whether the impact of peer-assisted in vivo exposure is enhanced when offered at the beginning of treatment as opposed to waiting until the point of dropout.

Development and Implementation of a Digital Quality Measure of Emergency Cancer Diagnosis.

Missed and delayed cancer diagnoses are common, harmful, and often preventable. Automated measures of quality of cancer diagnosis are lacking but could identify gaps and guide interventions. We developed and implemented a digital quality measure (dQM) of cancer emergency presentation (EP) using electronic health record databases of two health systems and characterized the measure's association with missed opportunities for diagnosis (MODs) and mortality. On the basis of literature and expert input, we defined EP as a new cancer diagnosis within 30 days after emergency department or inpatient visit. We identified EPs for lung cancer and colorectal cancer (CRC) in the Department of Veterans Affairs (VA) and Geisinger from 2016 to 2020. We validated measure accuracy and identified preceding MODs through standardized chart review of 100 records per cancer per health system. Using VA's longitudinal encounter and mortality data, we applied logistic regression to assess EP's association with 1-year mortality, adjusting for cancer stage and demographics. Among 38,565 and 2,914 patients with lung cancer and 14,674 and 1,649 patients with CRCs at VA and Geisinger, respectively, our dQM identified EPs in 20.9% and 9.4% of lung cancers, and 22.4% and 7.5% of CRCs. Chart reviews revealed high positive predictive values for EPs across sites and cancer types (72%-90%), and a substantial percent represented MODs (48.8%-84.9%). EP was associated with significantly higher odds of 1-year mortality for lung cancer and CRC (adjusted odds ratio, 1.78 and 1.83, respectively, 95% CI, 1.63 to 1.86 and 1.61 to 2.07). A dQM for cancer EP was strongly associated with both mortality and MODs. The findings suggest a promising automated approach to measuring quality of cancer diagnosis in US health systems.

Interprofessional Curriculum Delivery: Experience of a Primary Care Education Program.

Few post-graduate training programs offer a comprehensive curriculum that includes structured clinical experiences to teach interprofessional care. To address this need, the United States Department of Veterans Affairs, Office of Academic Affiliations funded the Centers of Excellence in Primary Care Education (CoEPCE) from 2011-2019 to provide interprofessional curricula for health profession trainees (HPTs), including physician residents, nurse practitioner residents, pharmacy residents, and psychology residents. We examined changes over time in curricular domains, system impacts, and program practices based on HPT survey data and the qualitative evaluation of narrative feedback. An annual survey was administered to participants. Indirect standardized ratios were calculated for interprofessional professional education (IPE) program domains, system impacts, and program practices. Qualitative responses were coded based on curricular domains and key program components. The study cohort included 369 HPTs. Site and profession standardized indirect ratios across all professions indicated improvements in curricular domains, system impacts, and program practices, with significant differences observed for associated health HPTs as compared to other HPTs for performance improvement. Qualitative data indicated that profession was associated with differences in perceptions of the curriculum. Although improvements occurred over time, our findings support the need for the thoughtful consideration of profession-specific identity characteristics when designing interprofessional curricula.

The US Department of Veterans Affairs: Disparities in Disability Compensation Approval Rates for ethnic minority Veterans, what is the Way Forward?

Introduction and Background: The U.S. Department of Veteran Affairs (VA) provides social services to eligible military veterans, including education, rehabilitation, healthcare, and compensation payments. However, the VA has faced challenges in administration management claims, with significant disparities in initial claim approval rates between racial and ethnic groups. Minority veterans, including African Americans, Asian Americans/Pacific Islanders, Hispanics, Native Americans/Alaska Natives, and Native Hawaiians, may qualify for numerous benefits. Briefly describe the research problem or question, providing context for the study. Objectives or Research Questions: How disparities in disability compensation approval rates among ethnic minority veterans compared to white veterans within the US Department of Veterans Affairs and mitigate strategies?" The study's main objective is to address disability compensation approval rate disparities for ethnic minority veterans by identifying causes, assessing impact, recommending solutions, ensuring equity, and monitoring progress. Methodology: The study analyzed disability compensation approval rates for minority veterans within the Department of Veterans Affairs (VA) using a quantitative research design. Data was collected from VA administrative records and databases. A representative sample of 100 claim applications was selected. Descriptive statistical analysis revealed significant disparities in approval rates, controlling for age and disability severity. Results: The study found that minority veterans had the lowest approval rate for disability claims, at 61%, compared to 75% for white veterans. Conclusion: The Department of Veteran Affairs (VA) has been criticized for racial disparities in disability compensation claims, with white veterans receiving the highest approval rates and African American veterans receiving the lowest. The VA's leadership's negligence and failure to address these disparities have led to systematic benefit obstruction for minority veterans. The study recommends enhancing training programs, implementing an equity action plan, and developing standardized guidelines for all veterans.

Using brief reflections to capture and evaluate end-user engagement: a case example using the COMPASS study

BackgroundUse of participatory research methods is increasing in research trials. Once partnerships are established with end-users, there is less guidance about processes research teams can use to successfully incorporate end-user feedback. The current study describes the use of a brief reflections process to systematically examine and evaluate the impact of end-user feedback on study conduct.MethodsThe Comparative Effectiveness of Trauma-Focused and Non-Trauma- Focused Treatment Strategies for PTSD among those with Co-Occurring SUD (COMPASS) study was a randomized controlled trial to determine the effectiveness of trauma-focused psychotherapy versus non-trauma-focused psychotherapy for Veterans with co-occurring posttraumatic stress disorder and substance use disorder who were entering substance use treatment within the Department of Veterans Affairs. We developed and paired a process of “brief reflections” with our end-user engagement methods as part of a supplemental evaluation of the COMPASS study engagement plan. Brief reflections were 30-minute semi-structured discussions with the COMPASS Team following meetings with three study engagement panels about feedback received regarding study issues. To evaluate the impact of panel feedback, 16 reflections were audio-recorded, transcribed, rapidly analyzed, and integrated with other study data sources.ResultsBrief reflections revealed that the engagement panels made recommended changes in eight areas: enhancing recruitment; study assessment completion; creating uniformity across Study Coordinators; building Study Coordinator connection to Veteran participants; mismatch between study procedures and clinical practice; therapist skill with patients with active substance use; therapist burnout; and dissemination of study findings. Some recommendations positively impact study conduct while others had mixed impact. Reflections were iterative and led to emergent processes that included revisiting previously discussed topics, cross-pollination of ideas across panels, and sparking solutions amongst the Team when the panels did not make any recommendations or recommendations were not feasible.ConclusionsWhen paired with end-user engagement methods, brief reflections can facilitate systematic examination of end-user input, particularly when the engagement strategy is robust. Reflections offer a forum of accountability for researchers to give careful thought to end-user recommendations and make timely improvements to the study conduct. Reflections can also facilitate evaluation of these recommendations and reveal end-user-driven strategies that can effectively improve study conduct.Trial registrationClinicalTrials.gov (NCT04581434) on October 9, 2020; https://clinicaltrials.gov/ct2/show/study/NCT04581434?term=NCT04581434&draw=2&rank=1.

No client left behind: A meta-analysis of premature termination from psychotherapy in U.S. service members and veterans.

Dropout has been identified as a significant problem among military populations seeking psychotherapy (Goetter et al., 2015; Hoge et al., 2014), yet an overall estimate of its exact prevalence and predictors does not exist. The aims of the current meta-analysis were to estimate outpatient psychotherapy dropout rates for this population and evaluate potential moderators of this event. In total, 283 articles-comprising data from 719,465 U.S. service members and veterans-met all inclusion criteria and were included in the meta-analysis. The average weighted dropout rate for all outpatient therapies was 25.6%, 95% CI [22.4%, 29.2%], and prediction interval [1.9%, 85.9%]. Furthermore, dropout was 27.0% for cognitive behavioral therapies (CBTs), 25.3% for trauma treatments, 27.6% for the Department of Veterans Affairs (VA), 28.9% for individual therapies, and 9.8% for intensive outpatient settings. Findings from metaregression analyses using mixed-effects models indicated that higher dropout was linked with the following after accounting for other moderators: younger age, CBTs, nonmanualized approaches, VA versus Department of Defense settings, individual versus group therapies, and weekly versus intensive outpatient formats. Dropout was not linked with other client, therapist, treatment, and research variables. Taken together, dropout estimates were obtained for a range of military populations and treatment characteristics, including theoretical orientation, presenting concern, setting, and therapy formats. These estimates may provide potential benchmarks for therapists, administrators, and policymakers serving military populations. Leveraging dropout prevention strategies with at-risk groups highlighted in this study may enhance mental health care outcomes for this high-need population. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Implementation of a Pilot PharmD Medication Optimization Telehealth Clinic Within a Veterans Affairs System.

Background Patients older than 65 years of age with an anticipated life-expectancy of 12 months or less may have complex medication regimens and an increased risk of adverse drug reactions, and drug-drug interactions. Within the Department of Veterans Affairs, a commonly used medication optimization model is known as the VIONE methodology. Objective This project aimed to pilot implementation of board-certified clinical pharmacist practitioners utilizing the VIONE model within a patient-aligned care team targeting patients 65 years of age and older. Methods The population was identified through the VIONE dashboards. Veteran inclusion criteria included five or more medications, a VIONE risk score of 5 or greater, and CAN scores of greater than 90. The project team reached out via telephone to the patients for a medication regimen review and a 14-day follow-up call. Primary outcomes were quantity of medications discontinued per patient, classes of medications that were discontinued, number and encounter time spent, and cost avoidance over 1 year. Secondary outcomes were VIONE classification of medications, VIONE discontinuation reason, number of recommendations given and accepted by primary provider, and safety analysis. Results There were 53 patients who were successfully contacted via telephone. The top four most discontinued medication classes included 1) vitamins/supplements, 2) ophthalmology medications, 3) gastrointestinal medications, and 4) non-controlled analgesic medications. During the project period the potential cost avoidance over 1 year was $17,716. CONCLUSION: This project demonstrated that usage of VIONE methodology ensures medication optimization with minimal harm and provides significant cost savings in the ambulatory care setting.

The effcacy of short-term tetrahydrobiopterin administration to improve locomotor muscle microvascular function in heart failure with preserved ejection fraction

Background: Patients with heart failure with preserved ejection fraction (HFpEF) exhibit locomotor muscle microvascular dysfunction due partly to reduced nitric oxide (NO) bioavailability. Tetrahydrobiopterin (BH4) is a requisite cofactor for the enzymatic production of NO by NO synthase (NOS). BH4 insuffciency promotes NOS uncoupling, which reduces NO production and augments cellular oxidative stress. Given the potential of BH4 to improve NO bioavailability, we tested the hypothesis that short-term BH4 administration would improve locomotor muscle microvascular function in patients with HFpEF. Methods: Eight patients with HFpEF (74±7 years; 31.3±4.9 kg/m2) participated in a randomized, double-blind, crossover study, having consumed either BH4 (Sapropterin, 10 mg/kg) or placebo for 10 days, separated by a 14-day washout period. Locomotor muscle microvascular function was assessed as leg blood flow (LBF) and leg vascular conductance (LVC) responses to passive leg movement (PLM) before (pre) and after (post) each treatment. PLM-induced LBF and LVC responses were expressed as peak change (Δpeak) or total hyperemic response (area under the curve above baseline; AUC). Results: LBFΔpeak did not change following BH4 (267 ± 136 mL/min vs. 250 ± 101 mL/min) or placebo (317 ± 119 mL/min vs. 269 ± 97 mL/min) administration (pre vs. post; p&gt;0.05). Similarly, LVCΔpeak was unchanged following either BH4 (396 ± 165 mL/min/100mmHg vs. 465 ± 180 mL/min/100mmHg) or placebo (579 ± 238 mL/min/100mmHg vs. 496 ± 185 mL/min/100mmHg) administration (pre vs. post; p&gt;0.05). The changes in LBFAUC and LVCAUC were not affected by either treatment (LBFAUC; BH4: Δ91 ± 103 mL vs. Δ82 ± 69 mL; placebo: Δ148 ± 119 mL vs. Δ87 ± 81 mL; LVCAUC; BH4: Δ65 ± 55 mL/100mmHg vs. Δ98 ± 78 mL/100mnHg; placebo: Δ182 ± 127 mL/100mmHg vs. Δ105 ± 94 mL/100mmHg) (pre vs. post; p&gt;0.05). Conclusion: Short-term BH4 administration did not improve locomotor muscle microvascular function in patients with HFpEF. This project was funded, in part, by the National Institutes of Health (HL118313, D.W.W.; T32HL139451, K.B.; the U.S. Department of Veterans Affairs (I01RX001311, D.W.W.; IK2RX003670, to K.B.), and the American Heart Association (18POST33960192; K.B.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Brief Repetitive Pressure Overload Elicits a Fibrosis-Independent Reduction in Left Ventricular Diastolic Compliance in Swine

Objective: We have previously shown that swine subjected to repetitive pressure overload (RPO) via daily 2-hr infusions of phenylephrine (PE) develop a reduction in left ventricular (LV) diastolic compliance that coincides with increased interstitial myocardial fibrosis. The objective of the present study was to determine if brief episodes of RPO produce a similar cardiac phenotype. Methods: Swine (n=6) were subjected to a single 30-min PE infusion (300 μg/min) to determine if brief pressure overload causes myocardial injury (circulating cardiac troponin I; cTnI), inflammation (IL-6), and cardiac dysfunction (echocardiography). A separate group of swine (n=5) were subsequently instrumented with an indwelling venous catheter to enable daily 30-min PE infusions for 2 weeks (“Brief RPO”). LV diastolic compliance (ΔLVEDV/ΔLVEDP during PE) and interstitial fibrosis (picrosirius red staining) were compared to values derived from swine subjected to prolonged RPO (2-hr PE/day; n=8) and age-matched controls (n=8). Results: A single episode of brief pressure overload led to an increase in circulating cTnI (from 22±6 ng/L at baseline to 365±12 ng/L 3-hours post-PE) and IL-6 (from 10±2 to 34±4 pg/mL), along with a transient reduction in LV ejection fraction (from 65±2 to 45±5 %, all p&lt;0.05). Brief RPO led to a significant reduction in LV diastolic compliance (ΔLVEDV/ΔLVEDP: 0.59±0.13 mL/mmHg vs. 1.87±0.12 mL/mmHg in controls; p&lt;0.01) that was nearly identical to that observed after prolonged RPO (0.58±0.17 mL/mmHg, p=0.95). Surprisingly, in contrast to prolonged RPO (10.0±1.4% collagen) the brief RPO-induced reduction in LV compliance was not accompanied by an increase in interstitial fibrosis (5.0±0.3 % collagen vs. 5.0±0.3 % collagen in controls, p=0.95). Conclusion: Brief pressure overload initially causes myocardial injury and inflammation, with repetitive exposure leading to a reduction in LV compliance that is similar to that observed following prolonged RPO. However, the brief RPO-induced reduction in LV compliance occurs in the absence of fibrosis, suggesting that mechanisms of repetitive stretch-induced myocardial stiffening may depend on the duration of episodic pressure overload. Supported by funding from the U.S. Department of Veterans Affairs and National Institutes of Health. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Urocortin 2 Gene Transfer in Mice Improves Diastolic Function in Heart Failure with Preserved Ejection Fraction

Patients with heart failure and preserved ejection fraction (HFpEF) comprise about 50% of patients with heart failure in the US (&gt;3 million people). There are currently no treatments for HFpEF that prolong life, and few that reduce HF hospitalization rates. The Schlager BPH (Blood Pressure-High) mouse is a genetic model of hypertension, a major contributing factor in left ventricular (LV) diastolic dysfunction and HFpEF. This study test the hypothesis that intravenous (i.v.) delivery of a long-term expression vector encoding murine urocortin 2 (AAV8.m Ucn2) can improve LV diastolic function in mice with impaired LV diastolic function. Twelve male and 12 female BPH mice (21.3±0.5 g; 3.1±0.1 months-old) with an ejection fraction (EF) of 60±2% (echocardiography) were studied. Prior to Ucn2 gene transfer their unsedated systolic/diastolic blood pressures (tail cuff) were (183/146±2/7 mmHg, n=24), conforming the presence of severe hypertension. The BPH mice were separated into two groups (6M &amp; 6F in each group). One group (BPH + Ucn2) received AAV8.m Ucn2 (2x1013 gc/kg, i.v) and the other group (BPH) received saline, i.v. Seven weeks after randomization, LV EF showed a group difference (BPH: 54±2%, n=12; BPH+Ucn2: 74±2%, n=12; p&lt;.0001) that was same as with systolic/diastolic blood pressure (BPH: 183/154±4/4 mmHg, n=12; BPH +Ucn2: 142/117±4/4 mmHg; p&lt;0.0001). In addition, physiological studies conducted in vivo showed accelerated cardiac relaxation in the Ucn2-treated mice (see Tau in Table), indicating superior LV relaxation after Ucn2 gene transfer. Conclusion: Ucn2 gene transfer improves LV diastolic and systolic function in mice with HFpEF, indicating that such a strategy may be applicable in clinical settings. [Formula: see text] Merit grant from the Department of Veterans Affairs (I01 BX003774). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Experiences and Perceptions of Maternal Autonomy and Racism Among BIPOC Veterans Receiving Cesarean Sections

BackgroundPrevious studies of pregnant veterans enrolled in Department of Veterans Affairs (VA) care reveal high rates of cesarean sections among racial/ethnic minoritized groups, particularly in southern states. The purpose of this study was to better understand contributors to and veteran perceptions of maternal autonomy and racism among veterans receiving cesarean sections. MethodsWe conducted semi-structured interviews to understand perceptions of maternal autonomy and racism among 27 Black, Indigenous, People of Color (BIPOC) veterans who gave birth via cesarean section using VA maternity care benefits. ResultsOur study found that a substantial proportion (67%) of veterans had previous cesarean sections, ultimately placing them at risk for subsequent cesarean sections. More than 60% of veterans with a previous cesarean section requested a labor after cesarean (LAC) but were either refused by their provider or experienced complications that led to another cesarean section. Qualitative findings revealed the following: (1) differences in treatment by veterans’ race/ethnicity may reduce maternal agency, (2) many veterans felt unheard and uninformed regarding birthing decisions, (3) access to VA-paid doula care may improve maternal agency for BIPOC veterans during labor and birth, and (4) BIPOC veterans face substantial challenges related to social determinants of health. ConclusionFurther research should examine veterans’ perceptions of racism in obstetrical care, and the possibility of VA-financed doula care to provide additional labor support to BIPOC veterans.