Clinical features do not identify risk of progression from isolated postcapillary pulmonary hypertension to combined pre- and postcapillary pulmonary hypertension.

Pulmonary hypertension is a common sequelae of left heart failure and may present as isolated postcapillary pulmonary hypertension (Ipc-PH) or combined pre- and postcapillary pulmonary hypertension (Cpc-PH). Clinical features associated with progression from Ipc-PH to Cpc-PH have not yet been described. We extracted clinical data from patients who underwent right heart catheterizations (RHC) on two separate occasions. Ipc-PH was defined as mean pulmonary pressure >20 mmHg, pulmonary capillary wedge pressure >15 mmHg, and pulmonary vascular resistance (PVR) < 3 WU. Progression to Cpc-PH required an increase in PVR to ≥3 WU. We performed a retrospective cohort study with repeated assessments comparing subjects that progressed to Cpc-PH to subjects that remained with Ipc-PH. Of 153 patients with Ipc-PH at baseline who underwent a repeat RHC after a median of 0.7 years (IQR 0.2, 2.1), 33% (50/153) had developed Cpc-PH. In univariate analysis comparing the two groups at baseline, body mass index (BMI) and right atrial pressure were lower, while the prevalence of moderate or worse mitral regurgitation (MR) was higher among those who progressed. In age- and sex-adjusted multivariable analysis, only BMI (OR 0.94, 95% CI 0.90-0.99, p = 0.017, C = 0.655) and moderate or worse MR (OR 3.00, 95% CI 1.37-6.60, p = 0.006, C = 0.654) predicted progression, but with poor discriminatory power. This study suggests that clinical features alone cannot distinguish patients at risk for development of Cpc-PH and support the need for molecular and genetic studies to identify biomarkers of progression.

Effect of Nightly Lower Body Negative Pressure on Choroid Engorgement in a Model of Spaceflight-Associated Neuro-ocular Syndrome: A Randomized Crossover Trial.

IMPORTANCE: Astronauts returning from long-duration spaceflight experience ocular remodeling related to cephalad fluid shifts induced by microgravity. It is hypothesized that the absence of diurnal reductions in intracranial pressure in microgravity creates a low but persistent pressure gradient at the posterior aspect of the eye, which results in ocular remodeling and space-associated neuro-ocular syndrome (SANS) over many months. OBJECTIVE: To determine whether partial reintroduction of footward fluid shifts during simulated microgravity via lower body negative pressure (LBNP) during sleep attenuates choroid engorgement, an early marker of ocular remodeling related to SANS. DESIGN, SETTING, AND PARTICIPANTS: Between May 2019 and February 2020, participants with no major cardiovascular, kidney, or ophthalmic disease completed 3 days of supine (0°) bed rest with and 3 days without 8 hours of nightly LBNP in a randomized, crossover design. This single-center investigation took place at the UT Southwestern Medical Center. All analyses were conducted blinded to condition and time point. INTERVENTIONS: Eight hours of nightly LBNP (-20 mm Hg) vs no LBNP. MAIN OUTCOMES AND MEASURES: The primary outcome was the change in choroid area and volume after 3 days of bed rest measured by optical coherence tomography. RESULTS: Of 10 participants, 5 were female, the mean (SD) age was 29 (9) years, and the age range was 18 to 55 years. Central venous pressure increased from the seated to supine position (mean [SD], seated: -2.3 [2.0] vs supine: 6.9 [2.0] mm Hg; P < .001), leading to choroid engorgement over 3 days of bed rest (Δ area: +0.09 mm2 [95% CI, 0.04-0.13]; P = .001; Δ volume: +0.37 mm3 [95% CI, 0.19-0.55]; P = .001). Nightly LBNP caused a sustained reduction in supine central venous pressure (mean [SD], 5.7 [2.2] mm Hg to 1.2 [1.4 mm Hg]; P < .001) and attenuated the increase in choroid area (74%) (Δ: 0.02 mm2 [95% -0.02 to 0.06]; P = .01) and volume (53%) (Δ: 0.17 mm3 [95% CI, 0.01-0.34]; P = .05) compared with control. CONCLUSIONS AND RELEVANCE: Nightly LBNP reinstated a footward fluid shift and mitigated the increase in choroid area and volume. LBNP during sleep may be an effective countermeasure for ocular remodeling and SANS during long-duration space missions.

Daily generation of a footward fluid shift attenuates ocular changes associated with head-down tilt bed rest.

Astronauts have presented with a constellation of visual changes referred to as spaceflight-associated neuro-ocular syndrome (SANS). However, neither have early markers of microgravity-induced optic remodeling been fully identified nor have countermeasures been developed. To identify early markers of SANS, we studied 10 subjects with optical coherence tomography and ultrasonography when upright and supine and again after 24 h of 6° head-down tilt (HDT) bed rest. Upon acute transition from the upright to the supine position, choroid area (2.24 ± 0.53 to 2.28 ± 0.52 mm2, P = 0.001) and volume (9.51 ± 2.08 to 9.73 ± 2.08 mm3, P = 0.002) increased. After 24 h of HDT bed rest, subfoveal choroidal thickness (372 ± 93 to 381 ± 95 µm, P = 0.02), choroid area (2.25 ± 0.52 to 2.33 ± 0.54 mm2, P = 0.08), and volume (9.64 ± 2.03 to 9.82 ± 2.08 mm3, P = 0.08) increased relative to the supine position. Subsequently, seven subjects spent 3 days in -6°HDT bed rest to assess whether low-level lower body negative pressure (LBNP) could prevent the observed choroidal engorgement during bed rest. Maintaining the -6° HDT position for 3 days caused choroid area (Δ0.11 mm2, P = 0.05) and volume (Δ0.45 mm3, P = 0.003) to increase. When participants also spent 8 h daily under -20 mmHg LBNP, choroid volume still increased, but substantially (40%) less than in the control trial (Δ0.27 mm3, P = 0.05). Moreover, the increase in choroid area was diminished (Δ0.03 mm2, P = 0.13), indicating that low-level LBNP attenuates the choroid expansion associated with 3 days of -6° HDT bed rest. These data suggest that low-level LBNP may be an effective countermeasure for SANS.NEW & NOTEWORTHY Choroid measurements appear to be sensitive to changes in gravitational gradients, as well as periods of head-down tilt (HDT) bed rest, suggesting that they are potential indicators of early ocular remodeling and could serve to evaluate the efficacy of countermeasures for SANS. Eight hours of lower body negative pressure (LBNP) daily attenuates the choroid expansion associated with 3 days of strict -6° HDT bed rest, indicating that LBNP may be an effective countermeasure for SANS.

Medicine in Extreme Environments: A New Medical Student Elective Class for Wilderness, Aerospace, Hyperbaric, Exercise, and Combat Medicine.

We developed an elective course titled Medicine in Extreme Environments (MEE) at the University of Texas Southwestern Medical Center for first- and second-year medical students. This course covered physiology, research, clinical practice, and career guidance regarding the fields of wilderness, space, hyperbaric, combat, and exercise medicine. The primary aim was to generate interest in and awareness of these seldom covered fields of medicine by exposing medical students to these disciplines during their preclinical years. A postcourse questionnaire was implemented to investigate whether the MEE course increased awareness of, interest in, and knowledge in the fields of medicine included in the curriculum. Through 2 iterations of the class, a total of 67 students enrolled in the course, and 38 students completed the questionnaire. After course completion, 95% felt they better understood the work and lifestyle of the fields covered, 100% learned more about concepts of each field, and 74% agreed that the elective influenced the direction of their future careers to include some part of the fields emphasized. Although only a limited number of students enrolled in this course, these initial findings suggest that the MEE curriculum may have some utility in promoting awareness of and interest in these medical disciplines among students who attend the course. With continued student and faculty support, this course will likely be continued annually at our institution. We believe that certain aspects of this course may be useful in helping develop similar courses at other medical schools.

Ocular changes over 60 min in supine and prone postures.

Some astronauts are returning from long-duration spaceflight with structural ocular and visual changes. We investigated both the transient and sustained effects of changes in the direction of the gravity vector acting on the eye using changes in body posture. Intraocular pressure (IOP; measured by Perkins tonometer), ocular geometry (axial length, corneal thickness, and aqueous depth-noncontact biometer), and the choroid (volume and subfoveal thickness optical coherence tomography) were measured in 10 subjects (5 males and 5 females). Measures were taken over the course of 60 min and analyzed with repeated-measures analysis of covariance to assess the effects of posture and time. In the supine position, choroidal volume increased significantly with time (average value at <5 min = 8.8 ± 2.3 mm3, 60 min = 9.0 ± 2.4 mm3, P = 0.03). In the prone position, IOP and axial length increased with time (IOP at <5 min 15 ± 2.7 mmHg, 60 min = 19.8 ± 4.1 mmHg, P < 0.0001; axial length at <5 min = 24.29 ± 0.77 mm, 60 min = 24.31 ± 0.76 mm, P = 0.002). Each increased exponentially, with time constants of 5.3 and 14 min, respectively. Prone corneal thickness also increased with time (<5 min = 528 ± 35 µm, 60 min = 537 ± 35 µm3, P < 0.001). Aqueous depth was shortened in the prone position (baseline = 3.22 ± 0.31 mm, 60 min = 3.18 ± 0.32 mm, P < 0.0001) but did not change with time. The data show that changes in the gravity vector have pronounced transient and sustained effects on the geometry and physiology of the eye.NEW & NOTEWORTHY We show that gravity has pronounced transient and sustained effects on the eye by making detailed ocular measurements over 60 min in the supine and prone postures. These data inform our understanding of how gravitational forces can affect ocular structures, which is essential for hypothesizing how ocular changes could occur with microgravity exposure.