The Experts below are selected from a list of 23832 Experts worldwide ranked by ideXlab platform
Marlene Rabinovitch - One of the best experts on this subject based on the ideXlab platform.
-
interdependent serotonin transporter and receptor pathways regulate s100a4 mts1 a gene associated with Pulmonary Vascular Disease
Circulation Research, 2005Co-Authors: Allan Lawrie, Edda Spiekerkoetter, Eliana C Martinez, Noona Ambartsumian, John W Sheward, Margaret R Maclean, Anthony J Harmar, Ann Marie Schmidt, Eugene Lukanidin, Marlene RabinovitchAbstract:Heightened expression of the S100 calcium–binding protein, S100A4/Mts1, is observed in Pulmonary Vascular Disease. Loss of serotonin (5-hydroxytryptamine [5-HT]) receptors or of the serotonin transporter (SERT) attenuates Pulmonary hypertension in animals, and polymorphisms causing gain of SERT function are linked to clinical Pulmonary Vascular Disease. Because 5-HT induces release of S100β, we investigated the codependence of 5-HT receptors and SERT in regulating S100A4/Mts1 in human Pulmonary artery smooth muscle cells (hPA-SMC). 5-HT elevated S100A4/Mts1 mRNA levels and increased S100A4/Mts1 protein in hPA-SMC lysates and culture media. S100A4/Mts1 in the culture media stimulated proliferation and migration of hPA-SMC in a manner dependent on the receptor for advanced glycation end products. Treatment with SB224289 (selective antagonist of 5-HT 1B ), fluoxetine (SERT inhibitor), SERT RNA-interference, and iproniazid (monoamine oxidase-A inhibitor), blocked 5-HT–induced S100A4/Mts1. 5-HT signaling mediated phosphorylation (p) of extracellular signal–regulated kinase 1/2 (pERK1/2), but pERK1/2 nuclear translocation depended on SERT, monoamine oxidase activity, and reactive oxygen species. Nuclear translocation of pERK1/2 was required for pGATA-4–mediated transcription of S100A4/Mts1. These data provide evidence for a mechanistic link between the 5-HT pathway and S100A4/Mts1 in Pulmonary hypertension and explain how the 5-HT 1B receptor and SERT are codependent in regulating S100A4/Mts1.
-
tenascin c proliferation and subendothelial fibronectin in progressive Pulmonary Vascular Disease
American Journal of Pathology, 1997Co-Authors: Peter L Jones, Kyle Northcote Cowan, Marlene RabinovitchAbstract:Progressive Pulmonary hypertension is characterized by smooth muscle cell proliferation and migration leading to occlusive arterial lesions. Previously, using cultured smooth muscle cells, we demonstrated that epidermal growth factor (EGF)-dependent proliferation and migration are dependent on tenascin-C (Tn) and cellular fibronectin (Fn), respectively. In this study we applied immunohistochemistry to lung biopsy tissue from patients with congenital heart defects and Pulmonary hypertension to determine how the distribution and intensity of Tn, EGF, proliferating cell nuclear antigen (PCNA), and Fn expression related to arterial abnormalities. With mildly increased wall thickness, minimal Tn, PCNA, and EGF was evident. With progressive hypertrophy, moderately intense foci of Tn were apparent in the adventitia, periendothelium, and occasionally the media but not consistently co-distributing with EGF and PCNA. With obstructive lesions, intense neointimal Tn expression co-localized with EGF and PCNA. Fn accumulation in the periendothelium increased with medial hypertrophy and became more widespread in a diffuse pattern with neointimal formation. The neointima was predominantly composed of alpha-smooth-muscle-actin-positive cells, occasional inflammatory cells with no evidence of apoptosis. These studies are consistent with Tn modulating EGF-dependent neointimal smooth muscle cell proliferation and Fn providing a gradient for smooth muscle cell migration from media to neointima.
John H Newman - One of the best experts on this subject based on the ideXlab platform.
-
pvdomics a multi center study to improve understanding of Pulmonary Vascular Disease through phenomics
Circulation Research, 2017Co-Authors: Anna R Hemnes, Gerald J Beck, John H Newman, Aiden Abidov, Micheala A Aldred, John Barnard, Erika B Rosenzweig, Barry A Borlaug, Wendy K Chung, Suzy A A ComhairAbstract:The National Institutes of Health (NIH)/National Heart, Lung and Blood institute (NHLBI) launched an initiative, PVDOMICS (Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics) that aims to augment the current Pulmonary hypertension (PH) classification based on shared biological features. PVDOMICS will enroll 1500 participants with PH and Disease and healthy comparators. Enrollees will undergo deep clinical phenotyping, and blood will be acquired for comprehensive omic analyses that will focus on discovery of molecular-based subtypes of Pulmonary Vascular Disease (PVD) through application of high dimensional model-based clustering methods. In addition to an updated, molecular classification of PVD, the phenomic data generated will be a rich resource to the broad community of heart and lung Disease investigators. Editorial, see p 1106 PH is a hemodynamic condition that causes increased blood pressure in the Pulmonary arteries and the right heart leading to adverse clinical outcomes. The current World Symposium on Pulmonary Hypertension (WSPH) classification of PH is based on a combination of patient characteristics, clinical features, and cardioPulmonary hemodynamics, and these features are used to inform treatment options.1 Aside from heritable Pulmonary arterial hypertension, this classification is not tied to molecular or cellular pathobiologic mechanism to explain the pathogenesis of PH. The NIH has a vested interest in understanding the causes and natural history of PH, as well as the discovery of effective treatment options. Since the first large NIH registry of patients with Pulmonary arterial hypertension >30 years ago,2 significant advances in scientific knowledge and translational medicine have occurred, highlighting a need for updating the current clinical classification system. The NHLBI has sponsored several workshops focusing on PVD research strategic planning over the past decade. PVD encompasses PH and PVD without PH, for example, Pulmonary vasculitis and pathological Pulmonary Vascular remodeling without hemodynamic criteria for PH. Experts identified the need …
-
enhancing insights into Pulmonary Vascular Disease through a precision medicine approach a joint nhlbi cardioVascular medical research and education fund workshop report
American Journal of Respiratory and Critical Care Medicine, 2017Co-Authors: John H Newman, Stephen Y Chan, Stuart Rich, Gerald J Beck, John Barnard, Steven H Abman, John H Alexander, Raymond L Benza, Todd Bull, Hyung J ChunAbstract:The Division of Lung Diseases of the NHLBI and the CardioVascular Medical Education and Research Fund held a workshop to discuss how to leverage the anticipated scientific output from the recently launched “Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics” (PVDOMICS) program to develop newer approaches to Pulmonary Vascular Disease. PVDOMICS is a collaborative, protocol-driven network to analyze all patient populations with Pulmonary hypertension to define novel Pulmonary Vascular Disease (PVD) phenotypes. Stakeholders, including basic, translational, and clinical investigators; clinicians; patient advocacy organizations; regulatory agencies; and pharmaceutical industry experts, joined to discuss the application of precision medicine to PVD clinical trials. Recommendations were generated for discussion of research priorities in line with NHLBI Strategic Vision Goals that include: (1) A national effort, involving all the stakeholders, should seek to coordinate biosamples and b...
-
enhancing insights into Pulmonary Vascular Disease through a precision medicine approach a joint nhlbi cardioVascular medical research and education fund workshop report
American Journal of Respiratory and Critical Care Medicine, 2017Co-Authors: John H Newman, Stephen Y Chan, Stuart Rich, Gerald J Beck, John Barnard, Steven H Abman, John H Alexander, Raymond L Benza, Todd M Bull, Hyung J ChunAbstract:The Division of Lung Diseases of the NHLBI and the CardioVascular Medical Education and Research Fund held a workshop to discuss how to leverage the anticipated scientific output from the recently launched "Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics" (PVDOMICS) program to develop newer approaches to Pulmonary Vascular Disease. PVDOMICS is a collaborative, protocol-driven network to analyze all patient populations with Pulmonary hypertension to define novel Pulmonary Vascular Disease (PVD) phenotypes. Stakeholders, including basic, translational, and clinical investigators; clinicians; patient advocacy organizations; regulatory agencies; and pharmaceutical industry experts, joined to discuss the application of precision medicine to PVD clinical trials. Recommendations were generated for discussion of research priorities in line with NHLBI Strategic Vision Goals that include: (1) A national effort, involving all the stakeholders, should seek to coordinate biosamples and biodata from all funded programs to a web-based repository so that information can be shared and correlated with other research projects. Example programs sponsored by NHLBI include PVDOMICS, Pulmonary Hypertension Breakthrough Initiative, the National Biological Sample and Data Repository for PAH, and the National Precision Medicine Initiative. (2) A task force to develop a master clinical trials protocol for PVD to apply precision medicine principles to future clinical trials. Specific features include: (a) adoption of smaller clinical trials that incorporate biomarker-guided enrichment strategies, using adaptive and innovative statistical designs; and (b) development of newer endpoints that reflect well-defined and clinically meaningful changes. (3) Development of updated and systematic variables in imaging, hemodynamic, cellular, genomic, and metabolic tests that will help precisely identify individual and shared features of PVD and serve as the basis of novel phenotypes for therapeutic interventions.
-
high altitude disorders Pulmonary hypertension Pulmonary Vascular Disease the global perspective
Chest, 2010Co-Authors: M Qadar A Pasha, John H NewmanAbstract:Globally, it is estimated that > 140 million people live at a high altitude (HA), defined as > 2,500 m (8,200 ft), and that countless others sojourn to the mountains for work, travel, and sport. The distribution of exposure to HA is worldwide, including 35 million in the Andes and > 80 million in Asia, including China and central Asia. HA stress primarily is due to the hypoxia of low atmospheric pressure, but dry air, intense solar radiation, extreme cold, and exercise contribute to acute and chronic disorders. The acute disorders are acute mountain sickness (also known as soroche), HA cerebral edema, and HA Pulmonary edema (HAPE). Of these, HAPE is highly correlated with acute Pulmonary hypertension. The first chronic syndrome described in HA dwellers in Peru was chronic mountain sickness (Monge Disease), which has a large component of relative hypoventilation and secondary erythrocytosis. The prevalence of chronic mountain sickness in HA dwellers ranges from 1.2% in native Tibetans to 5.6% in Chinese Han; 6% to 8% in male residents of La Paz, Bolivia; and 15.6% in the Andes. Subacute mountain sickness is an exaggerated Pulmonary hypertensive response to HA hypoxia occurring over months, most often in infants and very young children. Chronic Pulmonary hypertension with heart failure but without hypoventilation is seen in Asia. Not only does HA Pulmonary hypertension exact health consequences for the millions affected, but also the mechanisms of Disease relate to Pulmonary hypertension associated with multiple other disorders. Genetic understanding of these disorders is in its infancy.
Steven H Abman - One of the best experts on this subject based on the ideXlab platform.
-
enhancing insights into Pulmonary Vascular Disease through a precision medicine approach a joint nhlbi cardioVascular medical research and education fund workshop report
American Journal of Respiratory and Critical Care Medicine, 2017Co-Authors: John H Newman, Stephen Y Chan, Stuart Rich, Gerald J Beck, John Barnard, Steven H Abman, John H Alexander, Raymond L Benza, Todd Bull, Hyung J ChunAbstract:The Division of Lung Diseases of the NHLBI and the CardioVascular Medical Education and Research Fund held a workshop to discuss how to leverage the anticipated scientific output from the recently launched “Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics” (PVDOMICS) program to develop newer approaches to Pulmonary Vascular Disease. PVDOMICS is a collaborative, protocol-driven network to analyze all patient populations with Pulmonary hypertension to define novel Pulmonary Vascular Disease (PVD) phenotypes. Stakeholders, including basic, translational, and clinical investigators; clinicians; patient advocacy organizations; regulatory agencies; and pharmaceutical industry experts, joined to discuss the application of precision medicine to PVD clinical trials. Recommendations were generated for discussion of research priorities in line with NHLBI Strategic Vision Goals that include: (1) A national effort, involving all the stakeholders, should seek to coordinate biosamples and b...
-
enhancing insights into Pulmonary Vascular Disease through a precision medicine approach a joint nhlbi cardioVascular medical research and education fund workshop report
American Journal of Respiratory and Critical Care Medicine, 2017Co-Authors: John H Newman, Stephen Y Chan, Stuart Rich, Gerald J Beck, John Barnard, Steven H Abman, John H Alexander, Raymond L Benza, Todd M Bull, Hyung J ChunAbstract:The Division of Lung Diseases of the NHLBI and the CardioVascular Medical Education and Research Fund held a workshop to discuss how to leverage the anticipated scientific output from the recently launched "Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics" (PVDOMICS) program to develop newer approaches to Pulmonary Vascular Disease. PVDOMICS is a collaborative, protocol-driven network to analyze all patient populations with Pulmonary hypertension to define novel Pulmonary Vascular Disease (PVD) phenotypes. Stakeholders, including basic, translational, and clinical investigators; clinicians; patient advocacy organizations; regulatory agencies; and pharmaceutical industry experts, joined to discuss the application of precision medicine to PVD clinical trials. Recommendations were generated for discussion of research priorities in line with NHLBI Strategic Vision Goals that include: (1) A national effort, involving all the stakeholders, should seek to coordinate biosamples and biodata from all funded programs to a web-based repository so that information can be shared and correlated with other research projects. Example programs sponsored by NHLBI include PVDOMICS, Pulmonary Hypertension Breakthrough Initiative, the National Biological Sample and Data Repository for PAH, and the National Precision Medicine Initiative. (2) A task force to develop a master clinical trials protocol for PVD to apply precision medicine principles to future clinical trials. Specific features include: (a) adoption of smaller clinical trials that incorporate biomarker-guided enrichment strategies, using adaptive and innovative statistical designs; and (b) development of newer endpoints that reflect well-defined and clinically meaningful changes. (3) Development of updated and systematic variables in imaging, hemodynamic, cellular, genomic, and metabolic tests that will help precisely identify individual and shared features of PVD and serve as the basis of novel phenotypes for therapeutic interventions.
-
Pulmonary hypertension and Vascular abnormalities in bronchoPulmonary dysplasia
Clinics in Perinatology, 2015Co-Authors: Peter M Mourani, Steven H AbmanAbstract:Despite advances in the care of preterm infants, these infants remain at risk bronchoPulmonary dysplasia (BPD), which results in prolonged need for supplemental oxygen, recurrent respiratory exacerbations, and exercise intolerance. Recent investigations have highlighted the important contribution of the developing Pulmonary circulation to lung development, showing that these infants are also at risk for Pulmonary Vascular Disease (PVD), including Pulmonary hypertension (PH) and Pulmonary Vascular abnormalities. Several epidemiologic studies have delineated the incidence of PH in preterm infants and the impact on outcomes. These studies have also highlighted gaps in the understanding of PVD in BPD.
-
early Pulmonary Vascular Disease in preterm infants at risk for bronchoPulmonary dysplasia
American Journal of Respiratory and Critical Care Medicine, 2015Co-Authors: Peter M Mourani, Marci K Sontag, Adel K Younoszai, Joshua I Miller, J Kinsella, Christopher D Baker, Brenda B Poindexter, David A Ingram, Steven H AbmanAbstract:Rationale: Pulmonary hypertension (PH) is associated with poor outcomes among preterm infants with bronchoPulmonary dysplasia (BPD), but whether early signs of Pulmonary Vascular Disease are associated with the subsequent development of BPD or PH at 36 weeks post-menstrual age (PMA) is unknown.Objectives: To prospectively evaluate the relationship of early echocardiogram signs of Pulmonary Vascular Disease in preterm infants to the subsequent development of BPD and late PH (at 36 wk PMA).Methods: Prospectively enrolled preterm infants with birthweights 500–1,250 g underwent echocardiogram evaluations at 7 days of age (early) and 36 weeks PMA (late). Clinical and echocardiographic data were analyzed to identify early risk factors for BPD and late PH.Measurements and Main Results: A total of 277 preterm infants completed echocardiogram and BPD assessments at 36 weeks PMA. The median gestational age at birth and birthweight of the infants were 27 weeks and 909 g, respectively. Early PH was identified in 42% ...
-
Pulmonary Vascular Disease in bronchoPulmonary dysplasia Pulmonary hypertension and beyond
Current Opinion in Pediatrics, 2013Co-Authors: Peter M Mourani, Steven H AbmanAbstract:Purpose of review Pulmonary hypertension contributes significantly to morbidity and mortality of chronic lung Disease of infancy, or bronchoPulmonary dysplasia (BPD). Advances in Pulmonary Vascular biology over the past few decades have led to new insights into the pathogenesis of BPD; however, many unique issues persist regarding our understanding of Pulmonary Vascular development and Disease in preterm infants at risk for chronic lung Disease. Recent findings Recent studies have highlighted the important contribution of the developing Pulmonary circulation to lung growth in the setting of preterm birth. These studies suggest that there is a spectrum of Pulmonary Vascular Disease (PVD) in BPD rather than a simple question of whether or not Pulmonary hypertension is present. Epidemiological studies underscore gaps in our understanding of PVD in the context of BPD, including universally accepted definitions, approaches to diagnosis and treatment, and patient outcomes. Unfortunately, therapeutic strategies for Pulmonary hypertension in BPD are based on small observational studies with poorly defined endpoints and rely on results from older children and adult studies. Yet, unique characteristics of this population create other potential risks for the adoption of these strategies. Summary Despite many recent advances, PVD remains an important contributor to poor outcomes in preterm infants with BPD. Substantial challenges persist, especially with regard to understanding mechanisms and the clinical approach to PVD. Future studies are needed to develop evidence-based definitions and clinical endpoints through which the pathophysiology can be investigated and potential therapeutic interventions evaluated.
Rabinovitch Marlene - One of the best experts on this subject based on the ideXlab platform.
-
Interdependent serotonin transporter and receptor pathways regulate S100A4/Mts1, a gene associated with Pulmonary Vascular Disease
American Heart Association Inc., 2005Co-Authors: Lawrie Allan, Spiekerkoetter Edda, Martinez, Eliana C., Ambartsumian Noona, Sheward W. John, Maclean, Margaret R., Harmar, Anthony J., Schmidt Ann-marie, Lukanidin Eugene, Rabinovitch MarleneAbstract:Heightened expression of the S100 calcium–binding protein, S100A4/Mts1, is observed in Pulmonary Vascular Disease. Loss of serotonin (5-hydroxytryptamine [5-HT]) receptors or of the serotonin transporter (SERT) attenuates Pulmonary hypertension in animals, and polymorphisms causing gain of SERT function are linked to clinical Pulmonary Vascular Disease. Because 5-HT induces release of S100β, we investigated the codependence of 5-HT receptors and SERT in regulating S100A4/Mts1 in human Pulmonary artery smooth muscle cells (hPA-SMC). 5-HT elevated S100A4/Mts1 mRNA levels and increased S100A4/Mts1 protein in hPA-SMC lysates and culture media. S100A4/Mts1 in the culture media stimulated proliferation and migration of hPA-SMC in a manner dependent on the receptor for advanced glycation end products. Treatment with SB224289 (selective antagonist of 5-HT1B), fluoxetine (SERT inhibitor), SERT RNA-interference, and iproniazid (monoamine oxidase-A inhibitor), blocked 5-HT–induced S100A4/Mts1. 5-HT signaling mediated phosphorylation (p) of extracellular signal–regulated kinase 1/2 (pERK1/2), but pERK1/2 nuclear translocation depended on SERT, monoamine oxidase activity, and reactive oxygen species. Nuclear translocation of pERK1/2 was required for pGATA-4–mediated transcription of S100A4/Mts1. These data provide evidence for a mechanistic link between the 5-HT pathway and S100A4/Mts1 in Pulmonary hypertension and explain how the 5-HT1B receptor and SERT are codependent in regulating S100A4/Mts1
Barry A Borlaug - One of the best experts on this subject based on the ideXlab platform.
-
comprehensive diagnostic evaluation of cardioVascular physiology in patients with Pulmonary Vascular Disease insights from the pvdomics program
Circulation-heart Failure, 2020Co-Authors: W Wilson H Tang, Anna R Hemnes, Erika B Rosenzweig, Barry A Borlaug, Paul M Hassoun, Jennifer Wilcox, Miriam Jacob, Robert P Frantz, Nicholas S Hill, Evelyn M HornAbstract:Background: Invasive hemodynamic evaluation through right heart catheterization plays an essential role in the diagnosis, categorization, and risk stratification of patients with Pulmonary hyperten...
-
exercise unmasks distinct pathophysiologic features in heart failure with preserved ejection fraction and Pulmonary Vascular Disease
European Heart Journal, 2018Co-Authors: Yogesh N V Reddy, Vojtech Melenovsky, Thomas M Gorter, Masaru Obokata, Barry A BorlaugAbstract:Aims Pulmonary hypertension (PH) and Pulmonary Vascular Disease (PVD) are common and associated with adverse out- comes in heart failure with preserved ejection fraction (HFpEF). Little is known about the impact of PVD on the pathophysiology of exercise intolerance. Methods and results Heart failure with preserved ejection fraction patients (n= 161) with elevated Pulmonary capillary wedge pressure (>= 15 mmHg) at rest were classified into three groups: non-PH-HFpEF (n = 21); PH but no PVD (isolated post-capillary PH, IpcPH; n = 95); and PH with PVD (combined post- and pre-capillary PH, CpcPH; n = 45). At rest, CpcPH-HFpEF patients had more right ventricular (RV) dysfunction and lower Pulmonary arterial (PA) compliance compared to all other groups. While right atrial pressure (RAP) and left ventricular transmural pressure (LVTMP) were similar in HFpEF with and without PH or PVD at rest, CpcPH-HFpEF patients demonstrated greater increase in RAP, enhanced ventricular interdependence, and paradoxical reduction in LVTMP during exercise, differing from all other groups (P <0.05). Lower PA compliance was correlated with greater increase in RAP with exercise. During exercise, CpcPH-HFpEF patients displayed an inability to enhance cardiac output, reduction in forward stroke volume, and blunted augmentation in RV systolic performance, changes that were coupled with marked limitation in aerobic capacity. Conclusion Heart failure with preserved ejection fraction patients with PVD demonstrate unique haemodynamic limitations during exercise that constrain aerobic capacity, including impaired recruitment of LV preload due to excessive right heart congestion and blunted RV systolic reserve. Interventions targeted to this distinct pathophysiology require testing in patients with HFpEF and PVD.
-
pvdomics a multi center study to improve understanding of Pulmonary Vascular Disease through phenomics
Circulation Research, 2017Co-Authors: Anna R Hemnes, Gerald J Beck, John H Newman, Aiden Abidov, Micheala A Aldred, John Barnard, Erika B Rosenzweig, Barry A Borlaug, Wendy K Chung, Suzy A A ComhairAbstract:The National Institutes of Health (NIH)/National Heart, Lung and Blood institute (NHLBI) launched an initiative, PVDOMICS (Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics) that aims to augment the current Pulmonary hypertension (PH) classification based on shared biological features. PVDOMICS will enroll 1500 participants with PH and Disease and healthy comparators. Enrollees will undergo deep clinical phenotyping, and blood will be acquired for comprehensive omic analyses that will focus on discovery of molecular-based subtypes of Pulmonary Vascular Disease (PVD) through application of high dimensional model-based clustering methods. In addition to an updated, molecular classification of PVD, the phenomic data generated will be a rich resource to the broad community of heart and lung Disease investigators. Editorial, see p 1106 PH is a hemodynamic condition that causes increased blood pressure in the Pulmonary arteries and the right heart leading to adverse clinical outcomes. The current World Symposium on Pulmonary Hypertension (WSPH) classification of PH is based on a combination of patient characteristics, clinical features, and cardioPulmonary hemodynamics, and these features are used to inform treatment options.1 Aside from heritable Pulmonary arterial hypertension, this classification is not tied to molecular or cellular pathobiologic mechanism to explain the pathogenesis of PH. The NIH has a vested interest in understanding the causes and natural history of PH, as well as the discovery of effective treatment options. Since the first large NIH registry of patients with Pulmonary arterial hypertension >30 years ago,2 significant advances in scientific knowledge and translational medicine have occurred, highlighting a need for updating the current clinical classification system. The NHLBI has sponsored several workshops focusing on PVD research strategic planning over the past decade. PVD encompasses PH and PVD without PH, for example, Pulmonary vasculitis and pathological Pulmonary Vascular remodeling without hemodynamic criteria for PH. Experts identified the need …
-
lung congestion in chronic heart failure haemodynamic clinical and prognostic implications
European Journal of Heart Failure, 2015Co-Authors: Vojtech Melenovsky, Yogesh N V Reddy, Mads J Andersen, Krystof Andress, Barry A BorlaugAbstract:Aims The goal of the study was to examine the prognostic impact, haemodynamic and clinical features associated with lung congestion in patients with chronic heart failure (HF). Methods and results HF patients (n = 186) and HF-free controls (n = 21) underwent right heart catheterization, echocardiography, Pulmonary function testing and chest radiography that was blindly scored for the presence and severity of lung oedema. Lung congestion correlated directly with Pulmonary Vascular resistance (PVR, P = 0.004) and inversely with Pulmonary artery (PA) compliance (P median) had 25% lower PA compliance and 25–35% higher PVR, transPulmonary gradients and PA pressures (40 vs. 32 mmHg, P < 0.001) despite marginally higher PA wedge pressure (PAWP; 22 vs. 19 mmHg, P = 0.002). Wet lung HF patients displayed more right ventricular (RV) dilatation and dysfunction, more restrictive ventilation and greater reduction of DLCO. The strongest correlates of lung congestion were NT-proBNP, haemoglobin, albumin, and glomerular filtration, all surpassing PAWP. After a median of 333 days (interquartile range 80–875), 59 patients (32%) died. Lung congestion was associated with reduced survival (P < 0.0001), even after adjusting for PAWP, NT-proBNP, anaemia, CAD and renal dysfunction. Conclusion Interstitial lung oedema is associated with Pulmonary Vascular Disease, RV overload and dysfunction and increased mortality in HF. These data reinforce the importance of aggressive decongestion in HF and suggest that novel agents aimed at reducing lung water may help to deter progression of Pulmonary Vascular Disease and biventricular HF.
