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Autonomic Nervous System in Pulmonary Arterial Hypertension: Time to Rest and Digest.
Hemnes AR, Brittain EL
(2018) Circulation 137: 925-927
MeSH Terms: Autonomic Nervous System, Familial Primary Pulmonary Hypertension, Humans, Hypertension, Pulmonary, Vascular Remodeling, Ventricular Dysfunction, Right
Added June 7, 2018
0 Communities
1 Members
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6 MeSH Terms
Diabetes Mellitus Associates with Increased Right Ventricular Afterload and Remodeling in Pulmonary Arterial Hypertension.
Whitaker ME, Nair V, Sinari S, Dherange PA, Natarajan B, Trutter L, Brittain EL, Hemnes AR, Austin ED, Patel K, Black SM, Garcia JGN, Yuan Md PhD JX, Vanderpool RR, Rischard F, Makino A, Bedrick EJ, Desai AA
(2018) Am J Med 131: 702.e7-702.e13
MeSH Terms: Diabetes Mellitus, Female, Heart Ventricles, Humans, Hypertension, Pulmonary, Male, Pulmonary Artery, Retrospective Studies, Risk Factors, Ventricular Dysfunction, Right, Ventricular Remodeling
Show Abstract · Added June 7, 2018
BACKGROUND - Diabetes mellitus is associated with left ventricular hypertrophy and dysfunction. Parallel studies have also reported associations between diabetes mellitus and right ventricular dysfunction and reduced survival in patients with pulmonary arterial hypertension. However, the impact of diabetes mellitus on the pulmonary vasculature has not been well characterized. We hypothesized that diabetes mellitus and hyperglycemia could specifically influence right ventricular afterload and remodeling in patients with Group I pulmonary arterial hypertension, providing a link to their known susceptibility to right ventricular dysfunction.
METHODS - Using an adjusted model for age, sex, pulmonary vascular resistance, and medication use, associations of fasting blood glucose, glycated hemoglobin, and the presence of diabetes mellitus were evaluated with markers of disease severity in 162 patients with pulmonary arterial hypertension.
RESULTS - A surrogate measure of increased pulmonary artery stiffness, elevated pulmonary arterial elastance (P = .012), along with reduced log(pulmonary artery capacitance) (P = .006) were significantly associated with the presence of diabetes mellitus in patients with pulmonary arterial hypertension in a fully adjusted model. Similar associations between pulmonary arterial elastance and capacitance were noted with both fasting blood glucose and glycated hemoglobin. Furthermore, right ventricular wall thickness on echocardiography was greater in pulmonary arterial hypertension patients with diabetes, supporting the link between right ventricular remodeling and diabetes.
CONCLUSION - Cumulatively, these data demonstrate that an increase in right ventricular afterload, beyond pulmonary vascular resistance alone, may influence right ventricular remodeling and provide a mechanistic link between the susceptibility to right ventricular dysfunction in patients with both diabetes mellitus and pulmonary arterial hypertension.
Copyright © 2018 Elsevier Inc. All rights reserved.
0 Communities
1 Members
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11 MeSH Terms
Fatty Acid Metabolic Defects and Right Ventricular Lipotoxicity in Human Pulmonary Arterial Hypertension.
Brittain EL, Talati M, Fessel JP, Zhu H, Penner N, Calcutt MW, West JD, Funke M, Lewis GD, Gerszten RE, Hamid R, Pugh ME, Austin ED, Newman JH, Hemnes AR
(2016) Circulation 133: 1936-44
MeSH Terms: Animals, Ceramides, Cohort Studies, Fatty Acids, Humans, Hypertension, Pulmonary, Mice, Mice, Transgenic, Prospective Studies, Triglycerides, Ventricular Dysfunction, Right
Show Abstract · Added April 22, 2016
BACKGROUND - The mechanisms of right ventricular (RV) failure in pulmonary arterial hypertension (PAH) are poorly understood. Abnormalities in fatty acid (FA) metabolism have been described in experimental models of PAH, but systemic and myocardial FA metabolism has not been studied in human PAH.
METHODS AND RESULTS - We used human blood, RV tissue, and noninvasive imaging to characterize multiple steps in the FA metabolic pathway in PAH subjects and controls. Circulating free FAs and long-chain acylcarnitines were elevated in PAH patients versus controls. Human RV long-chain FAs were increased and long-chain acylcarnitines were markedly reduced in PAH versus controls. With the use of proton magnetic resonance spectroscopy, in vivo myocardial triglyceride content was elevated in human PAH versus controls (1.4±1.3% triglyceride versus 0.22±0.11% triglyceride, P=0.02). Ceramide, a mediator of lipotoxicity, was increased in PAH RVs versus controls. Using an animal model of heritable PAH, we demonstrated reduced FA oxidation via failure of palmitoylcarnitine to stimulate oxygen consumption in the PAH RV.
CONCLUSIONS - Abnormalities in FA metabolism can be detected in the blood and myocardium in human PAH and are associated with in vivo cardiac steatosis and lipotoxicity. Murine data suggest that lipotoxicity may arise from reduction in FA oxidation.
© 2016 American Heart Association, Inc.
0 Communities
4 Members
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11 MeSH Terms
Right ventricular myocardial biomarkers in human heart failure.
di Salvo TG, Yang KC, Brittain E, Absi T, Maltais S, Hemnes A
(2015) J Card Fail 21: 398-411
MeSH Terms: Adult, Biomarkers, Female, Gene Expression Profiling, Genetic Markers, Heart Failure, Humans, Male, Middle Aged, RNA, Tissue Donors, Ventricular Dysfunction, Right
Show Abstract · Added April 14, 2015
BACKGROUND - Right ventricular (RV) dysfunction contributes to mortality in chronic heart failure (HF). However, the molecular mechanisms of RV failure remain poorly understood, and RV myocardial biomarkers have yet to be developed.
METHODS AND RESULTS - We performed RNA sequencing (RNA-seq) on 22 explanted human HF RVs and 5 unused donor human heart RVs (DON RV) and compared results to those recently reported from 16 explanted human LVs We used Bowtie-Tophat for transcript alignment and transcriptome assembly, DESeq for identification of differentially expressed genes (DEGs) and Ingenuity for exploration of gene ontologies. In the HF RV, RNA-seq identified 130,790 total RNA transcripts including 13,272 protein coding genes, 10,831 long non-coding RNA genes and 8,605 pseudogenes. There were 800-1000 DEGs between DON and HF RV comparison groups with differences concentrated in cytoskeletal, basement membrane, extracellular matrix (ECM), inflammatory mediator, hemostasis, membrane transport and transcription factor genes, lncRNAs and pseudogenes. In an unbiased approach, the top 10 DEGs SERPINA3, SERPINA5, LCN6, LCN10, STEAP4, AKR1C1, STAC2, SPARCL1, VSIG4 and F8 exhibited no overlap in read counts between DON and HF RVs, high sensitivities, specificities, predictive values and areas under the receiver operating characteristic curves. STEAP4, SPARCL1 and VSIG4 were differentially expressed between RVs and LVs, supporting their roles as RV-specific myocardial biomarkers.
CONCLUSIONS - Unbiased, comprehensive profiling of the RV transcriptome by RNA-seq suggests structural changes and abnormalities in inflammatory processes and yields specific, novel HF RV vs HF LV myocardial biomarkers not previously identified by more limited transcriptome profiling approaches.
Copyright © 2015 Elsevier Inc. All rights reserved.
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1 Members
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12 MeSH Terms
Serum endostatin is a genetically determined predictor of survival in pulmonary arterial hypertension.
Damico R, Kolb TM, Valera L, Wang L, Housten T, Tedford RJ, Kass DA, Rafaels N, Gao L, Barnes KC, Benza RL, Rand JL, Hamid R, Loyd JE, Robbins IM, Hemnes AR, Chung WK, Austin ED, Drummond MB, Mathai SC, Hassoun PM
(2015) Am J Respir Crit Care Med 191: 208-18
MeSH Terms: Biomarkers, Collagen Type XVIII, Endostatins, Exercise Test, Female, Follow-Up Studies, Humans, Hypertension, Pulmonary, Kaplan-Meier Estimate, Male, Middle Aged, Polymorphism, Single Nucleotide, Predictive Value of Tests, Prognosis, Proportional Hazards Models, ROC Curve, Severity of Illness Index, Ventricular Dysfunction, Right
Show Abstract · Added February 12, 2015
RATIONALE - Pulmonary arterial hypertension (PAH) is a medically incurable disease resulting in death from right ventricular (RV) failure. Both pulmonary vascular and RV remodeling are linked to dynamic changes in the microvasculature. Therefore, we hypothesized that circulating angiostatic factors could be linked to outcomes and represent novel biomarkers of disease severity in PAH.
OBJECTIVES - We sought to determine the relationship of a potent angiostatic factor, endostatin (ES), with disease severity and mortality in PAH. Furthermore, we assessed genetic predictors of ES expression and/or function and their association with outcomes in PAH.
METHODS - We measured levels of serum ES in two independent cohorts of patients with PAH. Contemporaneous clinical data included New York Heart Association functional class, 6-minute-walk distance, invasive hemodynamics, and laboratory chemistries.
MEASUREMENTS AND MAIN RESULTS - Serum ES correlated with poor functional status, decreased exercise tolerance, and invasive hemodynamics variables. Furthermore, serum ES was a strong predictor of mortality. A loss-of-function, missense variant in the gene encoding ES, Col18a1, was linked to lower circulating protein and was independently associated with reduced mortality.
CONCLUSIONS - Our data link increased expression of ES to disease severity in PAH and demonstrate a significant relationship with adverse outcomes. Circulating ES levels can be genetically influenced, implicating ES as a genetically determined modifier of disease severity impacting on survival. These observations support serum ES as a potential biomarker in PAH with the capacity to predict poor outcomes. More importantly, this study implicates Col18a1/ES as a potential new therapeutic target in PAH.
0 Communities
2 Members
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18 MeSH Terms
Echocardiographic assessment of the right heart in mice.
Brittain E, Penner NL, West J, Hemnes A
(2013) J Vis Exp :
MeSH Terms: Animals, Disease Models, Animal, Echocardiography, Familial Primary Pulmonary Hypertension, Heart Ventricles, Hypertension, Pulmonary, Lung, Mice, Ventricular Dysfunction, Right, Ventricular Function, Right
Show Abstract · Added February 28, 2014
Transgenic and toxic models of pulmonary arterial hypertension (PAH) are widely used to study the pathophysiology of PAH and to investigate potential therapies. Given the expense and time involved in creating animal models of disease, it is critical that researchers have tools to accurately assess phenotypic expression of disease. Right ventricular dysfunction is the major manifestation of pulmonary hypertension. Echocardiography is the mainstay of the noninvasive assessment of right ventricular function in rodent models and has the advantage of clear translation to humans in whom the same tool is used. Published echocardiography protocols in murine models of PAH are lacking. In this article, we describe a protocol for assessing RV and pulmonary vascular function in a mouse model of PAH with a dominant negative BMPRII mutation; however, this protocol is applicable to any diseases affecting the pulmonary vasculature or right heart. We provide a detailed description of animal preparation, image acquisition and hemodynamic calculation of stroke volume, cardiac output and an estimate of pulmonary artery pressure.
0 Communities
2 Members
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10 MeSH Terms
Episodic monoplane transesophageal echocardiography impacts postoperative management of the cardiac surgery patient.
Maltais S, Costello WT, Billings FT, Bick JS, Byrne JG, Ahmad RM, Wagner CE
(2013) J Cardiothorac Vasc Anesth 27: 665-9
MeSH Terms: APACHE, Cardiac Surgical Procedures, Cardiac Tamponade, Critical Care, Critical Illness, Echocardiography, Transesophageal, Fluid Therapy, Hemodynamics, Humans, Hypovolemia, Pericardial Effusion, Postoperative Care, Prospective Studies, Vasoconstrictor Agents, Ventricular Dysfunction, Right
Show Abstract · Added January 20, 2015
OBJECTIVE - A new slender, flexible, and miniaturized disposable monoplane transesophageal TEE probe has been approved for episodic hemodynamic transesophageal echocardiographic monitoring. The authors hypothesized that episodic monoplane TEE with a limited examination would help guide the postoperative management of high-risk cardiac surgery patients.
DESIGN - The authors analyzed the initial consecutive observational experience with the miniaturized transesophageal echocardiography monitoring system (ClariTEE, ImaCor, Uniondale, New York).
SETTING - Single institution in a university setting.
PARTICIPANTS - Unstable cardiac surgery patients.
INTERVENTIONS - The authors assessed fluid responsiveness, echocardiographic data, and concordance among hemodynamic data.
MEASUREMENTS AND MAIN RESULTS - From June 2010 to February 2011, 21 unstable cardiac surgery patients with postoperative instability were identified. Two patients (10%) required reoperation for bleeding and tamponade physiology. Right ventricular dysfunction was diagnosed by episodic TEE monitoring in 7 patients (33%), while hypovolemia was documented in 12 patients (57%). Volume responsiveness was documented in 11 patients. In this observational study, discordance between hemodynamic monitoring and episodic TEE was qualitatively observed in 14 patients (66%).
CONCLUSION - The authors demonstrated the ability of episodic monoplane TEE to identify discordance between hemodynamic monitoring to better define clinical scenarios in unstable cardiac surgery patients. For these challenging patients, limited episodic TEE assessment has become a cornerstone of ICU care in this institution.
Copyright © 2013 Elsevier Inc. All rights reserved.
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1 Members
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15 MeSH Terms
Percent emphysema and right ventricular structure and function: the Multi-Ethnic Study of Atherosclerosis-Lung and Multi-Ethnic Study of Atherosclerosis-Right Ventricle Studies.
Grau M, Barr RG, Lima JA, Hoffman EA, Bluemke DA, Carr JJ, Chahal H, Enright PL, Jain A, Prince MR, Kawut SM
(2013) Chest 144: 136-144
MeSH Terms: African Continental Ancestry Group, Aged, Aged, 80 and over, Asian Continental Ancestry Group, Cohort Studies, European Continental Ancestry Group, Female, Heart Ventricles, Hispanic Americans, Humans, Lung, Magnetic Resonance Imaging, Male, Middle Aged, Prevalence, Prospective Studies, Pulmonary Emphysema, Smoking, Spirometry, Tomography, X-Ray Computed, Ventricular Dysfunction, Right
Show Abstract · Added February 28, 2014
BACKGROUND - Severe COPD can lead to cor pulmonale and emphysema and is associated with impaired left ventricular (LV) filling. We evaluated whether emphysema and airflow obstruction would be associated with changes in right ventricular (RV) structure and function and whether these associations would differ by smoking status.
METHODS - The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRI on 5,098 participants without clinical cardiovascular disease aged 45 to 84 years. RV and emphysema measures were available for 4,188 participants. Percent emphysema was defined as the percentage of voxels below -910 Hounsfield units in the lung windows on cardiac CT scans. Generalized additive models were used to control for confounders and adjust for respective LV parameters.
RESULTS - Participants consisted of 13% current smokers, 36% former smokers, and 52% never smokers. Percent emphysema was inversely associated with RV end-diastolic volume, stroke volume, cardiac output, and mass prior to adjustment for LV measures. After adjustment for LV end-diastolic volume, greater percent emphysema was associated with greater RV end-diastolic volume (+1.5 mL, P=.03) among current smokers, smaller RV end-diastolic volume (-0.8 mL, P=.02) among former smokers, and similar changes among never smokers.
CONCLUSIONS - Percent emphysema was associated with smaller RV volumes and lower mass. The relationship of emphysema to cardiac function is complex but likely involves increased pulmonary vascular resistance, predominantly with reduced cardiac output, pulmonary hyperinflation, and accelerated cardiopulmonary aging.
1 Communities
1 Members
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21 MeSH Terms