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Reduced myocardial perfusion is common among subjects with ischemia and no obstructive coronary artery disease and heart failure with preserved ejection fraction: a report from the WISE-CVD continuation study
(OAE, 2022) Aldiwani, Haider; Nelson, Michael D.; Sharif, Behzad; Wei, Janet; Samuel, T. Jake; Suppogu, Nissi; Quesada, Odayme; Cook-Wiens, Galen; Gill, Edward; Szczepaniak, Lidia S.; Thomson, Louise E. J.; Tamarappoo, Balaji; Asif, Anum; Shufelt, Chrisandra; Berman, Daniel; Merz, C. Noel Bairey; Medicine, School of Medicine
Aim: Women with evidence of ischemia and no obstructive coronary artery disease (INOCA) have an increased risk of major adverse cardiac events, including heart failure with preserved ejection fraction (HFpEF). To investigate potential links between INOCA and HFpEF, we examined pathophysiological findings present in both INOCA and HFpEF.
Methods: We performed adenosine stress cardiac magnetic resonance imaging (CMRI) in 56 participants, including 35 women with suspected INOCA, 13 women with HFpEF, and 8 reference control women. Myocardial perfusion imaging was performed at rest and with vasodilator stress with intravenous adenosine. Myocardial perfusion reserve index was quantified as the ratio of the upslope of increase in myocardial contrast at stress vs. rest. All CMRI measures were quantified using CVI42 software (Circle Cardiovascular Imaging Inc). Statistical analysis was performed using linear regression models, Fisher's exact tests, ANOVA, or Kruskal-Wallis tests.
Results: Age (P = 0.007), Body surface area (0.05) were higher in the HFpEF group. Left ventricular ejection fraction (P = 0.02) was lower among the INOCA and HFpEF groups than reference controls after age adjustment. In addition, there was a graded reduction in myocardial perfusion reserve index in HFpEF vs. INOCA vs. reference controls (1.5 ± 0.3, 1.8 ± 0.3, 1.9 ± 0.3, P = 0.02), which was attenuated with age-adjustment.
Conclusion: Reduced myocardial perfusion reserve appears to be a common pathophysiologic feature in INOCA and HFpEF patients.
Polyphenic risk score shows robust predictive ability for long-term future suicidality
(Discover Mental Health, 2022-06-13) Cheng, M; Roseberry, Kyle; Choi, Y; Quast, L; Gaines, Madelynn; Sandusky, George; Kline, JA; Bogdan, Paul; Niculescu, Alexander
Suicides are preventable tragedies, if risk factors are tracked and mitigated. We had previously developed a new quantitative suicidality risk assessment instrument (Convergent Functional Information for Suicidality, CFI-S), which is in essence a simple polyphenic risk score, and deployed it in a busy urban hospital Emergency Department, in a naturalistic cohort of consecutive patients. We report a four years follow-up of that population (n = 482). Overall, the single administration of the CFI-S was significantly predictive of suicidality over the ensuing 4 years (occurrence- ROC AUC 80%, severity- Pearson correlation 0.44, imminence-Cox regression Hazard Ratio 1.33). The best predictive single phenes (phenotypic items) were feeling useless (not needed), a past history of suicidality, and social isolation. We next used machine learning approaches to enhance the predictive ability of CFI-S. We divided the population into a discovery cohort (n = 255) and testing cohort (n = 227), and developed a deep neural network algorithm that showed increased accuracy for predicting risk of future suicidality (increasing the ROC AUC from 80 to 90%), as well as a similarity network classifier for visualizing patient's risk. We propose that the widespread use of CFI-S for screening purposes, with or without machine learning enhancements, can boost suicidality prevention efforts. This study also identified as top risk factors for suicidality addressable social determinants.
Relaxin Inhibits Ventricular Arrhythmia and Asystole in Rats With Pulmonary Arterial Hypertension
(Frontiers Media, 2021-07-06) Martin, Brian; Vanderpool, Rebecca R.; Henry, Brian L.; Palma, Joshua B.; Gabris, Beth; Lai, Yen-Chun; Hu, Jian; Tofovic, Stevan P.; Reddy, Rajiv P.; Mora, Ana L.; Gladwin, Mark T.; Romero, Guillermo; Salama, Guy; Medicine, School of Medicine
Pulmonary arterial hypertension (PAH) leads to right ventricular cardiomyopathy and cardiac dysfunctions where in the clinical setting, cardiac arrest is the likely cause of death, in ~70% of PAH patients. We investigated the cardiac phenotype of PAH hearts and tested the hypothesis that the insulin-like hormone, Relaxin could prevent maladaptive cardiac remodeling and protect against cardiac dysfunctions in a PAH animal model. PAH was induced in rats with sugen (20 mg/kg), hypoxia then normoxia (3-weeks/each); relaxin (RLX = 0, 30 or 400 μg/kg/day, n ≥ 6/group) was delivered subcutaneously (6-weeks) with implanted osmotic mini-pumps. Right ventricle (RV) hemodynamics and Doppler-flow measurements were followed by cardiac isolation, optical mapping, and arrhythmia phenotype. Sugen-hypoxia (SuHx) treated rats developed PAH characterized by higher RV systolic pressures (50 ± 19 vs. 22 ± 5 mmHg), hypertrophy, reduced stroke volume, ventricular fibrillation (VF) (n = 6/11) and bradycardia/arrest (n = 5/11); both cardiac phenotypes were suppressed with dithiothreitol (DTT = 1 mM) (n = 0/2/group) or RLX (low or high dose, n = 0/6/group). PAH hearts developed increased fibrosis that was reversed by RLX-HD, but not RLX-LD. Relaxin decreased Nrf2 and glutathione transferases but not glutathione-reductase. High-dose RLX improved pulmonary arterial compliance (measured by Doppler flow), suppressed VF even after burst-pacing, n = 2/6). Relaxin suppressed VF and asystole through electrical remodeling and by reversing thiol oxidative stress. For the first time, we showed two cardiac phenotypes in PAH animals and their prevention by RLX. Relaxin may modulate maladaptive cardiac remodeling in PAH and protect against arrhythmia and cardiac arrest.
Microglial knockdown does not affect acute withdrawal but delays analgesic tolerance from oxycodone in male and female C57BL/6J mice
(Frontiers Media, 2022-12-16) El Jordi, Omar; Fischer, Kathryn D.; Meyer, Timothy B.; Atwood, Brady K.; Oblak, Adrian L.; Pan, Raymond W.; McKinzie, David L.; Pharmacology and Toxicology, School of Medicine
Opioid Use Disorder (OUD) affects approximately 8%–12% of the population. In dependent individuals, abrupt cessation of opioid taking results in adverse withdrawal symptoms that reinforce drug taking behavior. Considerable unmet clinical need exists for new pharmacotherapies to treat opioid withdrawal as well as improve long-term abstinence. The neuroimmune system has received much scientific attention in recent years as a potential therapeutic target to combat various neurodegenerative and psychiatric disorders including addiction. However, the specific contribution of microglia has not been investigated in oxycodone dependence. Chronic daily treatment with the CSF1R inhibitor Pexidartinib (PLX3397) was administered to knockdown microglia expression and evaluate consequences on analgesia and on naloxone induced withdrawal from oxycodone. In vivo results indicated that an approximately 40% reduction in brain IBA1 staining was achieved in the PLX treatment group, which was associated with a delay in the development of analgesic tolerance to oxycodone and maintained antinociceptive efficacy. Acute withdrawal behavioral symptoms, brain astrocyte expression, and levels of many neuroinflammatory markers were not affected by PLX treatment. KC/GRO (also known as CXCL1) was significantly enhanced in the somatosensory cortex in oxycodone‐treated mice receiving PLX. Microglial knock-down did not affect the expression of naloxoneinduced opioid withdrawal but affected antinociceptive responsivity. The consequences of increased KC/GRO expression within the somatosensory cortex due to microglial reduction during opioid dependence are unclear but may be important for neural pathways mediating opioid‐induced analgesia.
Corrigendum: Analyzing One Cell at a TIME: Analysis of Myeloid Cell Contributions in the Tumor Immune Microenvironment
(Frontiers Media, 2021-02-01) Davidov, Vitaliy; Jensen, Garrett; Mai, Sunny; Chen, Shu-Hsia; Pan, Ping-Ying; Radiation Oncology, School of Medicine
In the original article, we neglected to include the funder Texas A&M Open Access to Knowledge Fund (OAKFund), supported by the University Libraries, to VD; NIH R01 CA127483, R01 CA204191, R01 CA208703 to S-HC; and NIH R01 CA188610 to P-YP. S-HC is the Emily Hermann Chair in Immunology Research and this work was supported in part by that endowment.
The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.