scholarly journals EXPRESS: Experimental Design of the EDIPHY (Effects of Dehydroepiandrosterone in Pulmonary Hypertension) Trial

2021 ◽  
pp. 204589402198955
Author(s):  
Thomas Patrick Walsh ◽  
Grayson Baird ◽  
Michael K Atalay ◽  
Saurabh Agarwal ◽  
Daniel Arcuri ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Hypertension ◽  
Experimental Design ◽  
Sex Hormone ◽  
Pulmonary Vascular Disease ◽  
Double Blind ◽  
Adrenal Steroid ◽  
Blood Institute ◽  
Post Menopausal ◽  
Rv Function

Pulmonary arterial hypertension (PAH) remains life-limiting despite numerous approved vasodilator therapies. Right ventricular (RV) function determines outcome in PAH but no treatments directly target RV adaptation. PAH is more common in women, yet women have better RV function and survival as compared to men with PAH. Lower levels of the adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate ester are associated with more severe pulmonary vascular disease, worse RV function, and mortality independent of other sex hormones in men and women with PAH. DHEA has direct effects on nitric oxide (NO) and endothelin-1 (ET-1) synthesis and signaling, direct antihypertrophic effects on cardiomyocytes, and mitigates oxidative stress. EDIPHY (Effects of Dehydroepiandrosterone in Pulmonary Hypertension) is an on-going randomized double-blind placebo-controlled crossover trial of DHEA in men (n = 13) and pre- and post-menopausal women (n = 13) with Group 1 PAH funded by the National Heart, Lung and Blood Institute. We will determine whether orally administered DHEA 50 mg daily for 18 weeks affects RV longitudinal strain measured by cardiac magnetic resonance imaging, markers of RV remodeling and oxidative stress, NO and ET-1 signaling, sex hormone levels, other PAH intermediate end points, side effects and safety. The crossover design will elucidate sex-based phenotypes in PAH and whether active treatment with DHEA impacts NO and ET-1 biosynthesis. EDIPHY is the first clinical trial of an endogenous sex hormone in PAH. Herein we present the study’s rationale and experimental design.

Sickle Cell Disease and Pulmonary Hypertension: Addressing the Mixed Pathology and Special Considerations in Diagnosis and Treatment

2007 ◽  
Vol 6 (1) ◽  
pp. 39-44
Author(s):  
Harrison W. Farber ◽  
Mark Gladwin ◽  
Evelyn M. Horn ◽  
Myung H. Park
Keyword(s):  
New York ◽  
Pulmonary Hypertension ◽  
Vascular Disease ◽  
Clinical Medicine ◽  
Medical Center ◽  
Associate Professor ◽  
Pulmonary Vascular Disease ◽  
Vascular Medicine ◽  
Blood Institute ◽  
School Of Medicine

This discussion was moderated by Evelyn M. Horn, MD, Associate Professor of Clinical Medicine and Director, Pulmonary Vascular Disease, Center for Advanced Cardiac Care, Columbia University Medical Center, New York, New York. Panel members included Harrison W. Farber, MD, Director, Pulmonary Hypertension Center, Boston Medical Center, Boston University School of Medicine; Mark Gladwin, MD, Chief, Vascular Medicine Branch, National Heart, Lung, and Blood Institute, Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD; Myung H. Park, MD, Director, Pulmonary Vascular Disease Program, University of Maryland School of Medicine.

scholarly journals P1505 Echocardiographic assessment of different pulmonary hypertension groups

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
M Fontes Oliveira ◽  
M Trepa ◽  
R Costa ◽  
A Dias Frias ◽  
I Silveira ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Interventricular Septum ◽  
Pulmonary Vascular Disease ◽  
Eccentricity Index ◽  
Group 4 ◽  
Global Strain ◽  
Group 3 ◽  
Group 2 ◽  
Rv Function ◽  
Group 1

Abstract Introduction Noninvasive echocardiography evaluation of the right ventricle (RV) has been shown to have prognostic value in patients with pulmonary hypertension (PH). Different etiology groups might have different echocardiographic phenotypes. In this study, we aimed to study echocardiographic characterization of the different PH groups and its ability to predict pulmonary vascular disease severity. Methods We collected echocardiographic and right heart catheterization (RHC) data from 97 (75% female, age 65 ± 15 years) consecutive patients referred to an expert tertiary care referral PH centre from 12/2016 to 11/2018. Echocardiographic analysis was performed using Echo-Pac software from GE Healthcare®. Group 3 and 5 were not included in the group comparison analysis due to few patients included. Results Group 2 PH was the most frequent etiology of PH (35), followed by group 1 (26), group 4 (18), group 5 (3) and group 3 (2). The echocardiographic evaluation of this population as a whole showed borderline parameters of RV dysfunction (tricuspid annular plane systolic excursion (TAPSE) 18 ± 4 mm, fractional area change (FAC) 33 ± 10% and S’ tricuspid wave 10 ± 3 cm/sec). Mean RV global strain was -15 ± 5 and RV free wall strain was -17 ± 7. PH group 1 had a significantly lower FAC (26 ± 4%, p = 0.0025), higher eccentricity index (IE) (1.5 ± 0.1, p = 0.01), and more frequently RV outflow tract (RVOT) notching than other groups (62%, p = 0.012). Group 4 presented an intermedium echocardiographic phenotype between group 1 and 2, and showed more abnormal strain values than the other groups. Group 2 had fewer patients in sinus rhythm (atrial fibrillation in 34% of patients, p = 0.02), presented a thicker interventricular septum (11.3 ± 1.8, p = 0.014), a higher FAC (35 ± 3%, p = 0.0025), higher E mitral wave velocity (72 ± 6 cm/s, p < 0.001) and E/E’ ratio (12.7 ± 10.2, p = 0.006), and larger left (45 ± 3 cm3/m3, p < 0.01) and right atria (25 ± 2 cm2, p = 0.03). PH groups 1 and 4 had higher Pulmonary Vascular Resistance (PVR) and Pulmonary Mean Arterial Pressure (PMAP) values than group 2, which significantly correlated with echocardiographic RV function parameters as TAPSE, FAC, RV global strain and IE. In PH group 2, eccentricity index was the only predictor of PVR (β=4.1, p = 0.018). In this population, a left atria volume < 32.7 cm3/m2 (OR 4.25, CI 1.71 - 10.55) and a E/e’ ratio < 12 (OR 4.72, CI 2.05 - 10.87) predicted PECP < 15 mmHg. RV global strain > -17.1 predicted PVR > 3 wood (OR 3.46, CI 1.50 - 8.02) and PMAP > 20 mmHg (OR 4.92, CI 1.67 - 14.51). TAPSE < 18 mm predicted PVR > 3 wood (OR 7.41, CI 2.99 - 18.36, AUC 0.72). Conclusion Different PH groups present mild echocardiographic differences between them. PH group 1 presented with more echocardiographic signs of RV disfunction, and PH group 2 had higher FAC, E/E’ and larger right and left atria. RV function parameters predicted PVR in PH groups 1 and 4, and EI was the only predictor of PVR in PH group 2. Abstract P1505 Figure.

scholarly journals The Road Toward Precision in PH: Personal Omics, Phenomics, and Wearables—Oh My!

2018 ◽  
Vol 17 (4) ◽  
pp. 141-147
Author(s):  
Jason M. Elinoff ◽  
Michael A. Solomon
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Vascular Disease ◽  
Monitoring Device ◽  
Symptom Development ◽  
Clinical Classification ◽  
The Road ◽  
Blood Institute ◽  
National Heart Lung ◽  
Pulmonary Arterial ◽  
Vanderbilt University

The keynote address of the 2018 Pulmonary Hypertension Association (PHA) Scientific Sessions given by Dr Roham Zamanian, “From Clinical Classification to Precision-Phenotyping: Envisioning Precision Medicine in Pulmonary Hypertension,” was the perfect prelude to the final session of the symposium. In this session the speakers tackled the timely question: “Omics and Wearables in Pulmonary Hypertension: Are We There Yet?” Dr Michael Snyder of Stanford University described how longitudinal, integrative personal omics profiling that incorporate whole genome sequencing, multidimensional omics measurements, and data from wearables can be applied to: 1) determine what it means to be healthy; 2) potentially predict transitions from health to disease prior to symptom development; and 3) better monitor and treat chronic disease. Dr Anna Hemnes of Vanderbilt University shared promising preliminary data from the ongoing multicenter, collaborative PVDOMICS initiative (Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics), funded by the National Heart, Lung and Blood Institute (NHLBI) and PHA. Finally, Dr Raymond Benza of the Allegheny Health Network shared intriguing pilot data on the safety and utility of an implantable hemodynamic monitoring device, the CardioMEMS™ HF system, in patients with advanced pulmonary arterial hypertension (PAH).

Abstract 14287: Iron Deficiency is Associated With More Severe Pulmonary Vascular Disease in Pulmonary Hypertension Due to Chronic Lung Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jasmine Tatah ◽  
Marc R Pritzker ◽  
Thenappan Thenappan ◽  
Kurt W Prins
Keyword(s):  
Pulmonary Hypertension ◽  
Iron Deficiency ◽  
Lung Disease ◽  
Vascular Disease ◽  
Chronic Lung Disease ◽  
Pulmonary Vascular Disease ◽  
Iron Deficient ◽  
Pulmonary Arterial ◽  
Group 3 ◽  
Rv Function

Background: Iron deficiency promotes pulmonary vascular remodeling in pre-clinical models, and is associated with worse outcomes in pulmonary arterial hypertension. However, the consequences of iron deficiency in patients with pulmonary hypertension due to chronic lung disease (Group 3 PH) are unexplored. Methods: We studied 122 consecutive Group 3 PH patients from the University of Minnesota Pulmonary Hypertension Repository. Serum soluble transferrin receptor (sTR) levels quantified iron deficiency. We evaluated the relationship between iron deficiency and pulmonary vascular disease, right ventricular (RV) function, exercise capacity, and survival. Results: The iron deficient group (<4.8mg/L sTR) had significantly higher mean pulmonary arterial pressure (40±9 mmHg, n=59 vs. 44±13 mmHg, n=61; p =.02) and lower pulmonary arterial compliance (2.2±1.2 mL/mmHg, n=52 vs. 1.7±0.8 mL/mmHg, n=55; p =.01), but there was no difference in pulmonary vascular resistance. Moreover, there were trends for higher right atrial pressure (7±4 mmHg, n=58 vs. 9±6 mmHg, n=61; p =0.08) in iron deficient patients. However, iron deficiency did not significantly alter RV function by echocardiography, 6-minute walk distance, or survival. Conclusions: Iron deficiency in Group 3 PH is associated with worse pulmonary vascular disease. This suggests iron deficiency could contribute to pulmonary vascular disease in Group 3 PH, and future studies are needed to determine if iron replacement could be a therapy for this deadly type of PH.

Pulmonary Hypertension Roundtable: COPD, IPF, and Pulmonary Hypertension: A Clinician's Dilemma

2013 ◽  
Vol 12 (3) ◽  
pp. 145-151
Keyword(s):  
Pulmonary Hypertension ◽  
Rhode Island ◽  
Medical Center ◽  
Puget Sound ◽  
Health Science ◽  
Pulmonary Vascular Disease ◽  
University Hospitals ◽  
Science Center ◽  
University Of Texas ◽  
Transplant Program

On October 9, 2013, a group of experts met by telephone to discuss PH in the setting of COPD and IPF. The group consisting of guest editor of this issue Jeffrey Edelman, MD, Head, Lung Transplant Program VA Puget Sound Health System, University of Washington; Deborah J. Levine, MD, Director, Pulmonary Hypertension Center, University of Texas Health Science Center at San Antonio; James Klinger, MD, Director, Rhode Island Hospital Pulmonary Hypertension Center; and Robert Schilz, DO, PhD, Director of Pulmonary Vascular Disease and Lung Transplantation, University Hospitals, Case Medical Center; provided perspective and insight into how clinicians can approach these patients most effectively.

TA-65, A Telomerase Activator improves Cardiovascular Markers in Patients with Metabolic Syndrome

2018 ◽  
Vol 24 (17) ◽  
pp. 1905-1911 ◽  
Author(s):  
Maria Luz Fernandez ◽  
Minu Sara Thomas ◽  
Bruno S. Lemos ◽  
Diana M. DiMarco ◽  
Amanda Missimer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Plasma Lipids ◽  
Disease Risk ◽  
Glycosylated Hemoglobin ◽  
Cardiovascular Disease Risk ◽  
Hdl Cholesterol ◽  
Double Blind ◽  
Tnf Α ◽  
Luminex Technology

Background: Telomerase Activator 65 (TA-65), a compound extracted from Astragalus membranaceus has been used in Chinese traditional medicine for extending lifespan. Scarce information exists on the effects of TA-65 on parameters of metabolic syndrome (MetS). Methods: We recruited 40 patients with MetS to determine the effects of TA-65 on dyslipidemias, hypertension, and oxidative stress in this at-risk population. The study was a double-blind, randomized crossover design in which patients were allocated to consume either 16 mg daily of a TA-65 supplement or a placebo for 12 weeks. Following a 3-week washout, participants were allocated to the alternate treatment for an additional 12 weeks. Anthropometric and biological markers were measured at the end of each treatment. Plasma lipids, glucose, CReactive Protein (CRP), liver enzymes, and glycosylated hemoglobin were measured using a Cobas c-111. Inflammatory cytokines were measured by Luminex technology and markers of oxidative stress by the use of spectroscopy. Results: Compared to the placebo period, HDL cholesterol (HDL-C) was higher while body mass index, waist circumference, and the LDL/HDL ratio were lower (p < 0.05) during TA-65 treatment. In addition, plasma tumor necrosis factor-α (TNF-α) was lower during the TA-65 period (p< 0.05). Positive correlations were observed in changes between the placebo and the TA-65 periods in HDL-C and CRP (r = -0.511, p < 0.01), alanine aminotransferase (r = -0.61, p < 0.001) and TNF-α (r = -0.550, p < 0.001) suggesting that the favorable changes observed in HDL were associated with decreases in inflammation. Conclusion: TA-65 improved key markers of cardiovascular disease risk, which were also associated with reductions in inflammation.

CMR markers for early right ventricular dysfunction in precapillary pulmonary hypertension

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Vos ◽  
T Leiner ◽  
A.P.J Van Dijk ◽  
F.J Meijboom ◽  
G.T Sieswerda ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricle ◽  
Right Ventricular ◽  
Circumferential Strain ◽  
Peak Strain ◽  
Healthy Controls ◽  
Free Wall ◽  
Global Circumferential Strain ◽  
The Right ◽  
Rv Function

Abstract Introduction Precapillary pulmonary hypertension (pPH) causes right ventricular (RV) pressure overload inducing RV remodeling, often resulting in dysfunction and dilatation, heart failure, and ultimately death. The ability of the right ventricle to adequately adapt to increased pressure loading is key for patients' prognosis. RV ejection fraction (RVEF) by cardiac magnetic resonance (CMR) is related to outcome in pPH patients, but this global measurement is not ideal for detecting early changes in RV function. Strain analysis on CMR using feature tracking (FT) software provides a more detailed assessment, and might therefore detect early changes in RV function. Aim 1) To compare RV strain parameters in pPH patients and healthy controls, and 2) to compare strain parameters in a subgroup of pPH patients with preserved RVEF (pRVEF) and healthy controls. Methods In this prospective study, a CMR was performed in pPH patients and healthy controls. Using FT-software on standard cine images, the following RV strain parameters were analyzed: global, septal, and free wall longitudinal strain (GLS, sept-LS, free wall-LS), time to peak strain (TTP, as a % of the whole cardiac cycle), the fractional area change (FAC), global circumferential strain (GCS), global longitudinal and global circumferential strain rate (GLSR and GCSR, respectively). A pRVEF is defined as a RVEF &gt;50%. To compare RV strain parameters in pPH patients to healthy controls, the Mann-Whitney U test was used. Results 33 pPH-patients (55 [45–63] yrs; 10 (30%) male) and 22 healthy controls (40 [36–48] yrs; 15 (68%) male) were included. All RV strain parameters were significantly reduced in pPH patients compared to healthy controls (see table), except for GCS and GCSR. Most importantly, in pPH patients with pRVEF (n=8) GLS (−26.6% [−22.6 to −27.3] vs. −28.1% [−26.2 to −30.6], p=0.04), sept-LS (−21.2% [−19.8 to −23.2] vs. −26.0% [−24.0 to −27.9], p=0.005), and FAC (39% [35–44] vs. 44% [42–47], p=0.02) were still significantly impaired compared to healthy controls. The RV TTP was significantly increased in pPH patients compared to healthy controls (47% [44–57] vs. 40% [33–43], p≤0.001). Conclusions Several CMR-FT strain parameters of the right ventricle are impaired in pPH patients when compared to healthy controls. Moreover, even in pPH patients with a preserved RVEF multiple RV strain parameters (GLS, sept-LS, and FAC) remained significantly impaired, and TTP significantly prolonged, in comparison to healthy controls. This suggests that RV strain parameters may be used as an early marker of RV dysfunction in pPH patients. Funding Acknowledgement Type of funding source: None

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