Pulmonary hypertension across the spectrum of left heart and lung disease.

AIMS: Patients with pulmonary hypertension (PH) are grouped based upon clinical and haemodynamic characteristics. Groups 2 (G2, left heart disease [LHD]) and 3 (G3, lung disease or hypoxaemia) are most common. Many patients display overlapping characteristics of heart and lung disease (G2-3), but this group is not well-characterized. METHODS AND RESULTS: Patients with PH enrolled in the prospective, NHLBI-sponsored PVDOMICS network underwent intensive clinical, biomarker, imaging, gas exchange and exercise phenotyping. Patients with pure G2, pure G3, or overlapping G2-3 PH were compared across multiple phenotypic domains. Of all patients with predominant G2 (n = 136), 66 (49%) were deemed to have secondary lung disease/hypoxaemia contributors (G2/3), and of all patients categorized as predominant G3 (n = 172), 41 (24%) were judged to have a component of secondary LHD (G3/2), such that 107 had G2-3 (combined G2/3 and G3/2). As compared with G3, patients with G2 and G2-3 were more obese and had greater prevalence of hypertension, atrial fibrillation, and coronary disease. Patients with G2 and G2-3 were more anaemic, with poorer kidney function, more cardiac dysfunction, and higher N-terminal pro-B-type natriuretic peptide than G3. Lung diffusion was more impaired in G3 and G2-3, but commonly abnormal even in G2. Exercise capacity was severely and similarly impaired across all groups, with no differences in 6-min walk distance or peak oxygen consumption, and pulmonary vasoreactivity to nitric oxide did not differ. In a multivariable Cox regression model, patients with G2 had lower risk of death or transplant compared with G3 (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.30-0.86), and patients with G2-3 also displayed lower risk compared with G3 (HR 0.57, 95% CI 0.38-0.86). CONCLUSIONS: Overlap is common in patients with a pulmonary or cardiac basis for PH. While lung structure/function is clearly more impaired in G3 and G2-3 than G2, pulmonary abnormalities are common in G2, even when clinically judged as isolated LHD. Further study is required to identify optimal systematic evaluations to guide therapeutic innovation for PH associated with combined heart and lung disease. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02980887.

Corticosteroid treatment for persistent pulmonary infiltrates following COVID-19 infection: Clearing the fog?

BACKGROUND: Systemic corticosteroids have been shown to improve outcomes in severe coronavirus disease 2019 (COVID-19) pneumonia; however, their role in post-COVID-19 persistent lung abnormalities is not well defined. Here, we describe our experience with corticosteroids in patients with persistent lung infiltrates following COVID-19 infection. RESEARCH QUESTION: What is the efficacy of systemic corticosteroids in improving lung function and radiological abnormalities in patients following COVID-19 pneumonia? STUDY DESIGN AND METHODS: This is a single-center retrospective study evaluating patients with persistent respiratory symptoms and abnormal chest computed tomography findings. Patients were divided into two groups based on treatment with corticosteroids: "steroid group" and "nonsteroid group." Clinical data were collected from the electronic medical records. RESULTS: Between March 2020 and December 2021, 227 patients were seen in the post-COVID-19 pulmonary clinic, of which 75 were included in this study. The mean age was 56 years, 63% were female, and 75% were white. The main physiologic deficit was reduced Diffusing capacity of the Lungs for Carbon Monoxide (DLCO) at 72% (±22). On chest imaging, the most common findings were ground-glass opacities (91%) and consolidation (29%). Thirty patients received corticosteroid (steroid group) and 45 did not (nonsteroid group). Patients treated with corticosteroids had lower DLCO (DLCO [%]: steroid group 63 ± 17, nonsteroid group 78 ± 23; P = 0.005) and all had ground-glass opacities on imaging compared to 84% in the nonsteroid group (P = 0.04). At follow-up, patients in the steroid group (n = 16) had a significant improvement in spirometry and DLCO. In addition, there was a significant improvement with resolution of ground-glass opacities in both the groups (P < 0.05). CONCLUSION: The use of systemic corticosteroids in patients with persistent respiratory symptoms and radiological abnormalities post-COVID-19 was associated with significant improvement in pulmonary function testing and imaging. Prospective studies are needed to confirm whether these findings are the effect of corticosteroid therapy or disease evolution over time.

Blood Cholesterol and Triglycerides Associate with Right Ventricular Function in Pulmonary Hypertension.

Background: Blood lipids are dysregulated in pulmonary hypertension (PH). Lower high-density lipoproteins cholesterol (HDL-C) and low-density lipoproteins cholesterol (LDL-C) are associated with disease severity and death in PH. Right ventricle (RV) dysfunction and failure are the major determinants of morbidity and mortality in PH. This study aims to test the hypothesis that dyslipidemia is associated with RV dysfunction in PH. Methods: We enrolled healthy control subjects (n=12) and individuals with PH (n=30) (age: 18-65 years old). Clinical characteristics, echocardiogram, 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (PET) scan, blood lipids, including total cholesterol (TC), triglycerides (TG), lipoproteins (LDL-C and HDL-C), and N-terminal pro-B type Natriuretic Peptide (NT-proBNP) were determined. Results: Individuals with PH had lower HDL-C [PH, 41±12; control, 56±16 mg/dL, p<0.01] and higher TG to HDL-C ratio [PH, 3.6±3.1; control, 2.2±2.2, p<0.01] as compared to controls. TC, TG, and LDL-C were similar between PH and controls. Lower TC and TG were associated with worse RV function measured by RV strain (R=-0.43, p=0.02 and R=-0.37, p=0.05 respectively), RV fractional area change (R=0.51, p<0.01 and R=0.48, p<0.01 respectively), RV end-systolic area (R=-0.63, p<0.001 and R=-0.48, p<0.01 respectively), RV end-diastolic area: R=-0.58, p<0.001 and R=-0.41, p=0.03 respectively), and RV glucose uptake by PET (R=-0.46, p=0.01 and R=-0.30, p=0.10 respectively). NT-proBNP was negatively correlated with TC (R=-0.61, p=0.01) and TG (R=-0.62, p<0.02) in PH. Conclusion: These findings confirm dyslipidemia is associated with worse right ventricular function in PH.

Hematopoietic stem cells and extramedullary hematopoiesis in the lungs.

Hematopoietic stem cells are key players in hematopoiesis as the body maintains a physiologic steady state, and the signaling pathways and control mechanisms of these dynamic cells are implicated in processes from inflammation to cancer. Although the bone marrow is commonly regarded as the site of hematopoiesis and hematopoietic stem cell residence, these cells also circulate in the blood and reside in extramedullary tissues, including the lungs. Flow cytometry is an invaluable tool in evaluating hematopoietic stem cells, revealing their phenotypes and relative abundances in both healthy and diseased states. This review outlines current protocols and cell markers used in flow cytometric analysis of hematopoietic stem and progenitor cell populations. Specific niches within the bone marrow are discussed, as are metabolic processes that contribute to stem cell self-renewal and differentiation, as well as the role of hematopoietic stem cells outside of the bone marrow at physiologic steady state. Finally, pulmonary extramedullary hematopoiesis and its associated disease states are outlined. Hematopoiesis in the lungs is a new and emerging concept, and discovering ways in which the study of lung-resident hematopoietic stem cells can be translated from murine models to patients will impact clinical treatment.

Iron deficiency in pulmonary vascular disease: pathophysiological and clinical implications.

AIMS: Iron deficiency is common in pulmonary hypertension, but its clinical significance and optimal definition remain unclear. METHODS AND RESULTS: Phenotypic data for 1028 patients enrolled in the Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics study were analyzed. Iron deficiency was defined using the conventional heart failure definition and also based upon optimal cut-points associated with impaired peak oxygen consumption (peakVO2), 6-min walk test distance, and 36-Item Short Form Survey (SF-36) scores. The relationships between iron deficiency and cardiac and pulmonary vascular function and structure and outcomes were assessed. The heart failure definition of iron deficiency endorsed by pulmonary hypertension guidelines did not identify patients with reduced peakVO2, 6-min walk test, and SF-36 (P > 0.208 for all), but defining iron deficiency as transferrin saturation (TSAT) <21% did. Compared to those with TSAT ≥21%, patients with TSAT <21% demonstrated lower peakVO2 [absolute difference: -1.89 (-2.73 to -1.04) mL/kg/min], 6-min walk test distance [absolute difference: -34 (-51 to -17) m], and SF-36 physical component score [absolute difference: -2.5 (-1.3 to -3.8)] after adjusting for age, sex, and hemoglobin (all P < 0.001). Patients with a TSAT <21% had more right ventricular remodeling on cardiac magnetic resonance but similar pulmonary vascular resistance on catheterization. Transferrin saturation <21% was also associated with increased mortality risk (hazard ratio 1.63, 95% confidence interval 1.13-2.34; P = 0.009) after adjusting for sex, age, hemoglobin, and N-terminal pro-B-type natriuretic peptide. CONCLUSION: The definition of iron deficiency in the 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) pulmonary hypertension guidelines does not identify patients with lower exercise capacity or functional status, while a definition of TSAT <21% identifies patients with lower exercise capacity, worse functional status, right heart remodeling, and adverse clinical outcomes.

The First Pulmonary Hypertension Registry in the United Arab Emirates (UAEPH): Clinical Characteristics, Hemodynamic Parameters with Focus on Treatment and Outcomes for Patients with Group 1-PH.

BACKGROUND: The aim of this study is to present the first United Arab Emirates pulmonary hypertension registry of patients' clinical characteristics, hemodynamic parameters and treatment outcomes. METHOD: This is a retrospective study describing all the adult patients who underwent a right heart catheterization for evaluation of pulmonary hypertension (PH) between January 2015 and December 2021 in a tertiary referral center in Abu Dhabi, United Arab Emirates. RESULTS: A total of 164 consecutive patients were diagnosed with PH during the five years of the study. Eighty-three patients (50.6%) were World Symposium PH Group 1-PH; nineteen patients (11.6%) were Group 2-PH due to left heart disease; twenty-three patients (14.0%) were Group 3-PH due to chronic lung disease; thirty-four patients (20.7%) were Group 4-PH due to chronic thromboembolic lung disease, and five patients (3.0%) were Group 5-PH. Among Group 1-PH, twenty-five (30%) had idiopathic, twenty-seven (33%) had connective tissue disease, twenty-six (31%) had congenital heart disease, and five patients (6%) had porto-pulmonary hypertension. The median follow-up was 55.6 months. Most of the patients were started on dual then sequentially escalated to triple combination therapy. The 1-, 3- and 5-year cumulative probabilities of survival for Group 1-PH were 86% (95% CI, 75-92%), 69% (95% CI, 54-80%) and 69% (95% CI, 54-80%). CONCLUSIONS: This is the first registry of Group 1-PH from a single tertiary referral center in the UAE. Our cohort was younger with a higher percentage of patients with congenital heart disease compared to cohorts from Western countries but similar to registries from other Asian countries. Mortality is comparable to other major registries. Adopting the new guideline recommendations and improving the availability and adherence to medications are likely to play a significant role in improving outcomes in the future.

Metabolic endophenotype associated with right ventricular glucose uptake in pulmonary hypertension.

Alterations in metabolism and bioenergetics are hypothesized in the mechanisms leading to pulmonary vascular remodeling and heart failure in pulmonary hypertension (PH). To test this, we performed metabolomic analyses on 30 PH individuals and 12 controls. Furthermore, using 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography, we dichotomized PH patients into metabolic phenotypes of high and low right ventricle (RV) glucose uptake and followed them longitudinally. In support of metabolic alterations in PH and its progression, the high RV glucose group had higher RV systolic pressure (p < 0.001), worse RV function as measured by RV fractional area change and peak global longitudinal strain (both p < 0.05) and may be associated with poorer outcomes (33% death or transplantation in the high glucose RV uptake group compared to 7% in the low RV glucose uptake group at five years follow-up, log-ranked p = 0.07). Pathway enrichment analysis identified key metabolic pathways including fructose catabolism, arginine-nitric oxide metabolism, tricarboxylic acid cycle, and ketones metabolism. Integrative human protein-protein interactome network analysis of metabolomic and transcriptomic data identified key pathobiological pathways: arginine biosynthesis, tricarboxylic acid cycle, purine metabolism, hypoxia-inducible factor 1, and apelin signaling. These findings identify a PH metabolomic endophenotype, and for the first time link this to disease severity and outcomes.

A network medicine approach to investigation and population-based validation of disease manifestations and drug repurposing for COVID-19.

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to unprecedented social and economic consequences. The risk of morbidity and mortality due to COVID-19 increases dramatically in the presence of coexisting medical conditions, while the underlying mechanisms remain unclear. Furthermore, there are no approved therapies for COVID-19. This study aims to identify SARS-CoV-2 pathogenesis, disease manifestations, and COVID-19 therapies using network medicine methodologies along with clinical and multi-omics observations. We incorporate SARS-CoV-2 virus-host protein-protein interactions, transcriptomics, and proteomics into the human interactome. Network proximity measurement revealed underlying pathogenesis for broad COVID-19-associated disease manifestations. Analyses of single-cell RNA sequencing data show that co-expression of ACE2 and TMPRSS2 is elevated in absorptive enterocytes from the inflamed ileal tissues of Crohn disease patients compared to uninflamed tissues, revealing shared pathobiology between COVID-19 and inflammatory bowel disease. Integrative analyses of metabolomics and transcriptomics (bulk and single-cell) data from asthma patients indicate that COVID-19 shares an intermediate inflammatory molecular profile with asthma (including IRAK3 and ADRB2). To prioritize potential treatments, we combined network-based prediction and a propensity score (PS) matching observational study of 26,779 individuals from a COVID-19 registry. We identified that melatonin usage (odds ratio [OR] = 0.72, 95% CI 0.56-0.91) is significantly associated with a 28% reduced likelihood of a positive laboratory test result for SARS-CoV-2 confirmed by reverse transcription-polymerase chain reaction assay. Using a PS matching user active comparator design, we determined that melatonin usage was associated with a reduced likelihood of SARS-CoV-2 positive test result compared to use of angiotensin II receptor blockers (OR = 0.70, 95% CI 0.54-0.92) or angiotensin-converting enzyme inhibitors (OR = 0.69, 95% CI 0.52-0.90). Importantly, melatonin usage (OR = 0.48, 95% CI 0.31-0.75) is associated with a 52% reduced likelihood of a positive laboratory test result for SARS-CoV-2 in African Americans after adjusting for age, sex, race, smoking history, and various disease comorbidities using PS matching. In summary, this study presents an integrative network medicine platform for predicting disease manifestations associated with COVID-19 and identifying melatonin for potential prevention and treatment of COVID-19.

A Network Medicine Approach to Investigation and Population-based Validation of Disease Manifestations and Drug Repurposing for COVID-19.

The global Coronavirus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to unprecedented social and economic consequences. The risk of morbidity and mortality due to COVID-19 increases dramatically in the presence of co-existing medical conditions while the underlying mechanisms remain unclear. Furthermore, there are no proven effective therapies for COVID-19. This study aims to identify SARS-CoV-2 pathogenesis, diseases manifestations, and COVID-19 therapies using network medicine methodologies along with clinical and multi-omics observations. We incorporate SARS-CoV-2 virus-host protein-protein interactions, transcriptomics, and proteomics into the human interactome. Network proximity measure revealed underlying pathogenesis for broad COVID-19-associated manifestations. Multi-modal analyses of single-cell RNA-sequencing data showed that co-expression of ACE2 and TMPRSS2 was elevated in absorptive enterocytes from the inflamed ileal tissues of Crohn's disease patients compared to uninflamed tissues, revealing shared pathobiology by COVID-19 and inflammatory bowel disease. Integrative analyses of metabolomics and transcriptomics (bulk and single-cell) data from asthma patients indicated that COVID-19 shared intermediate inflammatory endophenotypes with asthma (including IRAK3 and ADRB2). To prioritize potential treatment, we combined network-based prediction and propensity score (PS) matching observational study of 18,118 patients from a COVID-19 registry. We identified that melatonin (odds ratio (OR) = 0.36, 95% confidence interval (CI) 0.22-0.59) was associated with 64% reduced likelihood of a positive laboratory test result for SARS-CoV-2. Using PS-matching user active comparator design, melatonin was associated with 54% reduced likelihood of SARS-CoV-2 positive test result compared to angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (OR = 0.46, 95% CI 0.24-0.86).

COVID-19 and pulmonary hypertension.

Pulmonary hypertension (PH) is a pulmonary vascular disease characterized by pulmonary arterial remodeling and vasoconstriction leading to elevated pulmonary artery pressure and, ultimately, right heart failure. So far, few cases of COVID-19 disease in patients with PH have been reported. Caution is warranted in interpreting this observation as data are evolving and several factors may influence the number of reported cases of PH and COVID-19. Social distancing and quarantine could play a role, especially for patients with chronic diseases who might be more vigilant of their potential for respiratory infection. In addition, PH is a rare disease, and because testing is not universal, we could be underestimating the number of cases. Other hypothetical factors to consider are the underlying pathophysiology of PH and the medications used to treat PH and their implications in COVID-19.

Interdependence of hypoxia and ß-adrenergic receptor signaling in pulmonary arterial hypertension.

The ß-adrenergic receptor (ßAR) exists in an equilibrium of inactive and active conformational states, which shifts in response to different ligands and results in downstream signaling. In addition to cAMP, ßAR signals to hypoxia-inducible factor 1 (HIF-1). We hypothesized that a ßAR-active conformation (R**) that leads to HIF-1 is separable from the cAMP-activating conformation (R*) and that pulmonary arterial hypertension (PAH) patients with HIF-biased conformations would not respond to a cAMP agonist. We compared two cAMP agonists, isoproterenol and salbutamol, in vitro. Isoproterenol increased cAMP and HIF-1 activity, while salbutamol increased cAMP and reduced HIF-1. Hypoxia blunted agonist-stimulated cAMP, consistent with receptor equilibrium shifting toward HIF-activating conformations. Similarly, isoproterenol increased HIF-1 and erythropoiesis in mice, while salbutamol decreased erythropoiesis. ßAR overexpression in cells increased glycolysis, which was blunted by HIF-1 inhibitors, suggesting increased ßAR leads to increased hypoxia-metabolic effects. Because PAH is also characterized by HIF-related glycolytic shift, we dichotomized PAH patients in the Pulmonary Arterial Hypertension Treatment with Carvedilol for Heart Failure trial (NCT01586156) based on right ventricular (RV) glucose uptake to evaluate ßAR ligands. Patients with high glucose uptake had more severe disease than those with low uptake. cAMP increased in response to isoproterenol in mononuclear cells from low-uptake patients but not in high-uptake patients' cells. When patients were treated with carvedilol for 1 wk, the low-uptake group decreased RV systolic pressures and pulmonary vascular resistance, but high-uptake patients had no physiologic responses. The findings expand the paradigm of ßAR activation and uncover a novel PAH subtype that might benefit from ß-blockers.

Endothelial Phenotype Evoked by Low Dose Carvedilol in Pulmonary Hypertension.

Background: The therapeutic benefits of ß-blockers are well established in left heart failure. The Pulmonary Arterial Hypertension Treatment with Carvedilol for Heart Failure [PAHTCH] study showed safety and possible benefit of carvedilol in pulmonary arterial hypertension (PAH) associated right heart failure over 6 months. This study aims at evaluating the short-term cardiovascular effects and early mechanistic biomarkers of carvedilol therapy. Methods: Thirty patients with pulmonary hypertension (PH) received low dose carvedilol (3.125 mg twice daily) for 1 week prior to randomization to placebo, low-dose, or dose-escalating carvedilol therapy. Echocardiography was performed at baseline and 1 week. Exercise capacity was assessed by 6 min walk distance (6MWD). The L-arginine/nitric oxide pathway and other biological markers of endothelial function were measured. Results: All participants tolerated 1 week of carvedilol without adverse effects. After 1 week of carvedilol, 6MWD and heart rate at peak exercise did not vary (both p > 0.1). Heart rate at rest and 1 min post walk dropped significantly (both p < 0.05) with a trend for increase in heart rate recovery (p = 0.08). Right ventricular systolic pressure (RVSP) decreased by an average of 13 mmHg (p = 0.002). Patients who had a decrease in RVSP of more than 10 mm Hg were defined as responders (n = 17), and those with a lesser drop as non-responders (n = 13). Responders had a significant drop in pulmonary vascular resistance (PVR) after 1 week of carvedilol (p = 0.004). In addition, responders had a greater decrease in heart rate at rest and 1 min post walk compared to non-responders (both p < 0.05). Responders had higher plasma arginine and global bioavailability of arginine at baseline compared to non-responders (p = 0.03 and p = 0.05, respectively). After 1 week of carvedilol, responders had greater increase in urinary nitrate (p = 0.04). Responders treated with carvedilol had a sustained drop in RVSP and PVR after 6 months of carvedilol with no change in cardiac output. Conclusions: Low-dose carvedilol for 1 week can potentially identify a PH responder phenotype that may benefit from ß-blockers that is associated with less endothelial dysfunction. Clinical Trial Registration: http://www.clinicaltrials.gov. identifier: NCT01586156.

Pulmonary arterial hypertension treatment with carvedilol for heart failure: a randomized controlled trial.

BACKGROUND: Right-sided heart failure is the leading cause of death in pulmonary arterial hypertension (PAH). Similar to left heart failure, sympathetic overactivation and ß-adrenoreceptor (ßAR) abnormalities are found in PAH. Based on successful therapy of left heart failure with ß-blockade, the safety and benefits of the nonselective ß-blocker/vasodilator carvedilol were evaluated in PAH. METHODS: PAH Treatment with Carvedilol for Heart Failure (PAHTCH) is a single-center, double-blind, randomized, controlled trial. Following 1-week run-in, 30 participants were randomized to 1 of 3 arms for 24 weeks: placebo, low-fixed-dose, or dose-escalating carvedilol. Outcomes included clinical measures and mechanistic biomarkers. RESULTS: Decreases in heart rate and blood pressure with carvedilol were well tolerated; heart rate correlated with carvedilol dose. Carvedilol-treated groups had no decrease in exercise capacity measured by 6-minute walk, but had lower heart rates at peak and after exercise, and faster heart rate recovery. Dose-escalating carvedilol was associated with reduction in right ventricular (RV) glycolytic rate and increase in ßAR levels. There was no evidence of RV functional deterioration; rather, cardiac output was maintained. CONCLUSIONS: Carvedilol is likely safe in PAH over 6 months of therapy and has clinical and mechanistic benefits associated with improved outcomes. The data provide support for longer and larger studies to establish guidelines for use of ß-blockers in PAH. TRIAL REGISTRATION: ClinicalTrials.gov NCT01586156FUNDING. This project was supported by NIH R01HL115008 and R01HL60917 and in part by the National Center for Advancing Translational Sciences, UL1TR000439.

Metabolic and Functional Evaluation of the Heart and Lungs in Pulmonary Hypertension by Gated 2-[18F]-Fluoro-2-deoxy-D-glucose Positron Emission Tomography.

Pulmonary hypertension (PH) is associated with a metabolic shift towards glycolysis in both the right ventricle and lung. This results in increased glucose uptake to compensate for the lower energy yield of glycolysis, which creates a potential for 2-[18F] fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) to be a useful tool in the evaluation of participants with PH. We investigated the utility of PET for PH by comparing FDG-PET uptake in the right ventricle and lungs in 30 participants with PH and eight healthy controls and correlating these measurements with echocardiographic (ECHO) measurements and other traditional assessments commonly used in PH. All participants underwent gated FDG-PET scanning in the fasting state, ECHO, six-minute walk test (6MWT), and blood draw for NT-proBNP. Participants also completed the CAMPHOR questionnaire. Right ventricular (RV) end-diastolic and end-systolic volumes, RV ejection fraction, and FDG uptake by PET were significantly different between PH and healthy controls and strongly correlated with plasma NT-proBNP levels and RV ECHO parameters including TAPSE, RV systolic pressure, Tei index, and global peak systolic strain. In addition, lung standardized uptake value (SUV) was also found to be significantly higher in participants with PH than healthy controls. However, lung SUV did not show any significant correlations with NT-proBNP levels, 6MWT, or functional and pressure measurements by ECHO. In this study, we demonstrated the ability to evaluate both lung and right heart metabolism and function in PH by using a single gated FDG-PET scan.