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Background: Exhaled volatile organic compounds (VOCs) can provide insight into various physiological and metabolic processes. Aim: The purpose of this study was to determine if exhaled VOCs would differ across disease severity in heart failure (HF) patients. Methods: We recruited 62 individuals who were classified as healthy control (CTL), admissions with fluid overload (DHF), NYHA class I-II or NYHA class II-III. Breath samples were collected using the ReCIVA Breath Sampler (Owlstone Medical Ltd) and analyzed using mass spectrometry and gas chromatography. Typical clinical characteristics were documented at the time of exhaled breath collection. Results: Data were obtained on 16 CTL, 21 DHF, 15 NYHA I-II and 10 NYHA II-III (characteristics shown in Table). For the HF groups, DHF, NYHA I-II and NYHA II-III, the %HPEFF were 32, 63 and 63% respectively. Regarding exhaled VOCs, we observed a stepwise increase in VOCs potentially linked to lipid peroxidation or fatty acid metabolism, such as pent-3-en-2-one, 2-pentanone, and 4-heptanone, as disease severity worsened. A similar trend was seen for sulphur containing compounds (methyl propyl sulfide, allyl methyl sulfide and 1(methyl thiol)-1 propene)), potentially providing insight into impaired hepatic or renal clearance in more advanced HF. The level of methyl pyruvate on breath also rose with increasing disease severity, which may reflect altered energy metabolism. Finally, gut microbiome-related VOCs (acetoin, 2,3-butanediol, and butyric anhydride) increased across severity groups, potentially reflecting dysbiosis in advanced disease. Conclusions: In a small pilot study aiming to identify potential exhaled breath biomarkers in HF, we observed significant differences in VOCs across disease severity. These compounds have been linked to lipid peroxidation, energy metabolism, liver and kidney function as well as microbial fermentation and short-chain fatty acid metabolism. Collectively, these data demonstrate the ability of breath omics to potentially stratify disease severity and provide additional biological insights into HF pathophysiology. Larger studies are needed to determine whether a breath biomarker panel could be established to quantify disease severity and predict decompensation risk in HF.

Abstract Rationale: Heart failure (HF) is often characterized by elevated left ventricular filling pressures (LVFP) and pulmonary congestion. However, LVFP may not always predict congestion. Pulmonary congestion can be quantified by computed tomography (CT) imaging. We hypothesized that extravascular lung water quantified by CT may differ in HF groups such as HF with preserved ejection fraction (HFpEF) vs HF with reduced ejection fraction (HFrEF), inpatients with acute decompensated heart failure (ADHF) vs stable and this would be related to echocardiography (echo) derived estimates of LVFP. Methods: We enrolled and studied 83 patients with HF who were either admitted or had a clinic visit at Mayo Clinic, Rochester, MN from May 2018 through March 2019. All subjects underwent comprehensive echo and supine thoracic CT scans. CT lung fluid was quantified and reported as proportion (%) of total lung volume. CT attenuation in lung tissue was also measured. LVFP was evaluated according to standardized echo diagnostic algorithms. Patients were stratified based on clinical diagnosis of HF as inpatients with HFpEF (n=26, 75.6±8.5yrs, M=50%, BMI=36.2±8.9kg/m2) inpatients with HFrEF (n=33, 75.6±14yrs, M=79%, BMI=31.1±9.1kg/m2), inpatients with ADHF (n=14, 72.6±14.5yrs, m=64.2%, BMI= 32.2±7.6Kg/m2) and stable outpatient HF controls (n=10, 65±13 yrs, m=90%, BMI= 29.5±5.2Kg/m2). All four groups were compared using one-way ANOVA followed by a post-hoc analysis. A correlation between lung fluid % and LVFP was performed using Spearman's correlation test. Results: When HF groups were compared according to CT % lung fluid, significant differences were found between HF groups (p=0.004). Post-hoc analysis revealed a significant difference in % lung fluid as HFrEF group had higher mean value in % lung fluid compared to HF control group (p=0.004). Similarly, ADHF group had higher mean % lung fluid compared to HF control group (p= 0.007). However, we found no correlation between LVFP and % lung fluid. The rightward shift in CT attenuation for HFpEF, HFrEF, and ADHF subjects, as displayed in figure 1, suggests greater levels of % lung water in these subjects compared to controls. Conclusion: These data suggest that CT measures of lung water differ in subgroups of HF patients and may not correlate with LVFP.

Growing evidence suggests that the larger conducting airways are smaller in women than men; however, evidence of this sex‐difference in airway geometry is yet to be demonstrated in a large cohort of adult, healthy non‐smokers. Furthermore, it is not known whether these sex differences persist after airway size is adjusted for its allometric relationship with absolute lung size. Purpose We examined the effect of sex on airway size in a large cohort of non‐smoking healthy adults after adjusting for the possible confounding effect of absolute lung size. Methods A total of 133 (75 men; 58 women) non‐smoking adults (50 ± 18 yrs) with normal pulmonary function (>80% pred.) participated in this study. Full thoracic CT scans were obtained in each participant during a breath‐hold at full inflation. Commercial software was used to automatically segment airways and assign 32 anatomical labels ranging from the 0 th to the 5 th generation. Intraluminal hydraulic diameters ( D h ) were obtained for each airway. An allometric relationship was assumed between D h and absolute lung size, as given by: D h = TLV β · e k , where TLV is the total lung volume at full inflation, β is the allometric scaling exponent, and k allowed for proportional effects of confounding variables. This allometric equation was log‐log transformed such that it could be examined using linear regression: e.g., ln( D h ) = β ·ln(TLV) + k . Sex, age and their interaction were allowed to contribute to both β and k as covariates. The model also included a term for reconstructed voxel size. Model averaging was used to provide parameter estimates of the log‐log transformed allometric equation. Results The allometric exponent, β , assigned to TLV was significant for all 32 anatomically labelled airways ( P < 0.05); neither sex nor age affected β . On the other hand, sex and age were significant mediators of k for the extra‐parenchymal airways only (Trachea, RMB, LMB, BronInt, see Figure 1, P < 0.05). Conclusions Our findings indicate that sex differences in D h remain present despite accounting for the allometric relationship between airway and lung size (see Figure 1). Importantly, however, this sex‐difference in airway size is seemingly confined to the extra‐parenchymal airways. Support or Funding Information This work was supported by NIH Grant HL71478. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Background It is documented that cognitive performance can diminish with altitude, but the sensitivity of specific tests have not been investigated. Our objective was to assess and compare cognitive performance from several tests and relate this to quality of sleep and acute mountain sickness (AMS). Methods During an Everest expedition, 3 cognitive tests (Stroop, Trail Making, and a proprietary motor accuracy test) were used along with a questionnaire to assess sleep and AMS. Six athlete climbers and 9 core team members were assessed pre and post‐expedition and at several time points during the expedition (up to 17,500 ft). Results To normalize for individual differences, scores were assessed as % change from baseline. There was no difference in the variation between repeated attempts in a single testing session (0.19<p<0.87), demonstrating that each test was reproducible. There was no decrement in test scores with altitude, nor was there an association with reported sleep quality. The Stroop performance was associated with AMS (p<0.05) and trending with headache (p< 0.15). The in‐house motor test trended towards an association with AMS and headache (p<0.15). However, the trail making test was not associated with AMS/headache. Conclusion With appropriate acclimatization, cognitive performance is maintained at altitude but is linked to presence of headache and AMS. Mayo Clinic and TNF.

Objective It is well documented that cognitive performance may be altered with ascent to altitude, but the association of various cognitive performance tests with symptoms of acute mountain sickness (AMS) is not well understood. Our objective was to assess and compare cognitive performance during a high-altitude expedition using several tests and to report the association of each test with AMS, headache, and quality of sleep. Methods During an expedition to Mount Everest, 3 cognitive tests (Stroop, Trail Making, and the real-time cognitive assessment tool, an in-house developed motor accuracy test) were used along with a questionnaire to assess health and AMS. Eight team members were assessed pre-expedition, postexpedition, and at several time points during the expedition. Results There were no significant differences ( P >.05) found among scores taken at 3 time points at base camp and the postexpedition scores for all 3 tests. Changes in the Stroop test scores were significantly associated with the odds of AMS ( P <.05). The logistic regression results show that the percent change from baseline for Stroop score (β = −5.637; P = .032) and Stroop attempts (β = −5.269; P = .049) are significantly associated with the odds of meeting the criteria for AMS. Conclusions No significant changes were found in overall cognitive performance at altitude, but a significant relationship was found between symptoms of AMS and performance in certain cognitive tests. This research shows the need for more investigation of objective physiologic assessments to associate with self-perceived metrics of AMS to gauge effect on cognitive performance.

We tested the hypothesis that changes in the arteriolar branching architecture contributed to increased running capacity of rats subjected to two-way artificial selection for intrinsic aerobic endurance treadmill running capacity resulting in strains of low-capacity and high-capacity endurance rats. Hearts and gastrocnemius muscles were harvested from each strain, and the microvasculature's branching geometry measured from micro-CT images. The vascular branching geometry of the hearts and skeletal muscle from the high capacity was indistinguishable from low-capacity rats. Our hypothesis was not supported. Neither remodeling nor an increase in arteriolar microvasculature branching appears to play a role in the enhanced performance of the high capacity rats. We are led to speculate that endothelial tolerance for shear stress and/or increased coupling of myocardial muscle fiber metabolic-to-contractile function is increased in the high-capacity runner strain to the effect of allowing either higher flow rate per unit volume of muscle or more efficient use of oxygen and nutrients in the high-capacity endurance rats.