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RESPIRATORY DISEASES (102 journals)                     

Showing 1 - 102 of 102 Journals sorted alphabetically
Advances in Respiratory Medicine     Open Access   (Followers: 7)
American Journal of Respiratory and Critical Care Medicine     Full-text available via subscription   (Followers: 255)
American Journal of Respiratory Cell and Molecular Biology     Full-text available via subscription   (Followers: 20)
American Review of Respiratory Disease     Full-text available via subscription   (Followers: 4)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1)
Annals of the American Thoracic Society     Full-text available via subscription   (Followers: 16)
Annals of Thoracic Medicine     Open Access   (Followers: 6)
Archivos de Bronconeumología     Full-text available via subscription  
Archivos de Bronconeumología (English Edition)     Full-text available via subscription   (Followers: 1)
Asthma Research and Practice     Open Access   (Followers: 1)
BMC Pulmonary Medicine     Open Access   (Followers: 4)
BMJ Open Respiratory Research     Open Access   (Followers: 5)
Breathe     Open Access   (Followers: 4)
Canadian Journal of Respiratory, Critical Care, and Sleep Medicine     Hybrid Journal  
Canadian Respiratory Journal     Open Access   (Followers: 2)
Case Reports in Pulmonology     Open Access   (Followers: 3)
Chest     Full-text available via subscription   (Followers: 100)
Chest Disease Reports     Open Access   (Followers: 2)
Chronic Respiratory Disease     Hybrid Journal   (Followers: 9)
Clinical Lung Cancer     Hybrid Journal   (Followers: 5)
Clinical Medicine Insights : Circulatory, Respiratory and Pulmonary Medicine     Open Access   (Followers: 3)
Clinical Pulmonary Medicine     Hybrid Journal   (Followers: 2)
COPD Research and Practice     Open Access   (Followers: 1)
COPD: Journal of Chronic Obstructive Pulmonary Disease     Hybrid Journal   (Followers: 15)
Current Opinion in Pulmonary Medicine     Hybrid Journal   (Followers: 10)
Current Pulmonology Reports     Hybrid Journal  
Current Research in Tuberculosis     Open Access   (Followers: 3)
Current Respiratory Care Reports     Hybrid Journal   (Followers: 1)
Current Respiratory Medicine Reviews     Hybrid Journal   (Followers: 5)
Der Pneumologe     Hybrid Journal   (Followers: 1)
Egyptian Journal of Chest Diseases and Tuberculosis     Open Access   (Followers: 3)
ERJ Open Research     Open Access   (Followers: 2)
Eurasian Journal of Pulmonology     Open Access  
European Clinical Respiratory Journal     Open Access   (Followers: 3)
European Respiratory Journal     Full-text available via subscription   (Followers: 38)
European Respiratory Review     Open Access   (Followers: 7)
Experimental Lung Research     Hybrid Journal  
Expert Review of Respiratory Medicine     Hybrid Journal   (Followers: 5)
Heart & Lung: The Journal of Acute and Critical Care     Hybrid Journal   (Followers: 11)
Heart, Lung and Circulation     Full-text available via subscription   (Followers: 9)
Indian Journal of Respiratory Care     Open Access   (Followers: 3)
Indian Journal of Tuberculosis     Full-text available via subscription  
Influenza and Other Respiratory Viruses     Open Access   (Followers: 3)
International Journal of Chronic Obstructive Pulmonary Disease     Open Access   (Followers: 3)
Journal of Association of Chest Physicians     Open Access   (Followers: 2)
Journal of Asthma     Hybrid Journal   (Followers: 4)
Journal of Asthma Allergy Educators     Hybrid Journal   (Followers: 4)
Journal of Bronchology & Interventional Pulmonology     Hybrid Journal   (Followers: 3)
Journal of Clinical Tuberculosis and Other Mycobacterial Diseases     Open Access  
Journal of Heart and Lung Transplantation     Hybrid Journal   (Followers: 12)
Journal of Respiratory Medicine     Open Access   (Followers: 4)
Journal of Respiratory Research     Open Access   (Followers: 1)
Journal of Tuberculosis Research     Open Access   (Followers: 1)
Jurnal Respirasi     Open Access  
Karger Kompass Pneumologie     Full-text available via subscription   (Followers: 1)
Kindheit und Entwicklung     Hybrid Journal  
Lung     Hybrid Journal   (Followers: 2)
Lung Cancer     Hybrid Journal   (Followers: 15)
Lung Cancer International     Open Access   (Followers: 2)
Lung Cancer: Targets and Therapy     Open Access   (Followers: 3)
Lung India     Open Access   (Followers: 1)
Multidisciplinary Respiratory Medicine     Open Access   (Followers: 4)
npj Primary Care Respiratory Medicine     Open Access   (Followers: 2)
Open Journal of Respiratory Diseases     Open Access   (Followers: 1)
Open Respiratory Medicine Journal     Open Access   (Followers: 1)
Paediatric Respiratory Reviews     Hybrid Journal   (Followers: 11)
Pediatric Quality & Safety     Open Access  
Pediatric Respirology and Critical Care Medicine     Open Access   (Followers: 1)
Pulmonary Circulation     Open Access   (Followers: 4)
Pulmonary Medicine     Open Access   (Followers: 2)
Pulmonary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 2)
Pulmonary Therapy     Open Access   (Followers: 1)
Pulmonology and Respiratory Research     Open Access   (Followers: 1)
Respiratory Care     Full-text available via subscription   (Followers: 10)
Respiratory Investigation     Full-text available via subscription  
Respiratory Medicine     Hybrid Journal   (Followers: 17)
Respiratory Medicine : X     Open Access  
Respiratory Medicine Case Reports     Open Access  
Respiratory Medicine CME     Hybrid Journal  
Respiratory Medicine Extra     Full-text available via subscription   (Followers: 1)
Respiratory Physiology & Neurobiology     Hybrid Journal   (Followers: 4)
Respiratory Research     Open Access   (Followers: 1)
Respirology     Hybrid Journal   (Followers: 5)
Respirology Case Reports     Open Access  
Revista Americana de Medicina Respiratoria     Open Access  
Revista Chilena de Enfermedades Respiratorias     Open Access  
Revista Inspirar     Open Access  
Revista ORL     Open Access  
Revista Portuguesa de Pneumologia     Open Access  
Sarcoidosis Vasculitis and Diffuse Lung Disese     Full-text available via subscription   (Followers: 3)
Seminars in Respiratory and Critical Care Medicine     Hybrid Journal   (Followers: 14)
Sleep Medicine Reviews     Hybrid Journal   (Followers: 17)
The Clinical Respiratory Journal     Hybrid Journal   (Followers: 3)
The International Journal of Tuberculosis and Lung Disease     Full-text available via subscription   (Followers: 8)
The Lancet Respiratory Medicine     Full-text available via subscription   (Followers: 32)
Therapeutic Advances in Chronic Disease     Open Access   (Followers: 7)
Therapeutic Advances in Respiratory Disease     Open Access   (Followers: 1)
Thorax     Hybrid Journal   (Followers: 37)
Translational Respiratory Medicine     Open Access   (Followers: 1)
Tuberculosis     Hybrid Journal   (Followers: 12)
Tuberculosis Research and Treatment     Open Access   (Followers: 3)
Пульмонология     Full-text available via subscription  

           

Similar Journals
Journal Cover
Journal of Heart and Lung Transplantation
Journal Prestige (SJR): 4.592
Citation Impact (citeScore): 5
Number of Followers: 12  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1053-2498
Published by Elsevier Homepage  [3161 journals]
  • RISK ASSESSMENT IN PULMONARY ARTERIAL HYPERTENSION (PAH): INSIGHTS FROM
           THE GRIPHON STUDY
    • Abstract: Publication date: Available online 21 January 2020Source: The Journal of Heart and Lung TransplantationAuthor(s): Olivier Sitbon, Kelly M. Chin, Richard N. Channick, Raymond L. Benza, Lilla Di Scala, Sean Gaine, Hossein-Ardeschir Ghofrani, Irene M. Lang, Vallerie V. McLaughlin, Ralph Preiss, Lewis J. Rubin, Gérald Simonneau, Victor F. Tapson, Nazzareno Galiè, Marius M. HoeperABSTRACTBackgroundApproaches to risk assessment in pulmonary arterial hypertension (PAH) include the non-invasive French risk assessment approach (number of low-risk criteria based on the ESC/ERS guidelines) and REVEAL 2.0 risk calculator. The prognostic and predictive value of these methods for morbidity/mortality was evaluated in the predominantly prevalent population of GRIPHON, the largest randomized controlled trial in PAH.MethodsGRIPHON randomized 1156 PAH patients to selexipag or placebo. Post-hoc analyses were performed on the primary composite endpoint of morbidity/mortality by number of low-risk criteria (WHO functional class I-II; 6-minute walk distance>440 m; N-terminal pro brain natriuretic peptide
       
  • Use of Direct Oral Anticoagulants after Heart Transplantation
    • Abstract: Publication date: Available online 21 January 2020Source: The Journal of Heart and Lung TransplantationAuthor(s): Erik J. Henricksen, Maxime Tremblay-Gravel, Yasbanoo Moayedi, Wenjia Yang, Roy Lee, Heather J. Ross, William Hiesinger, Jeffrey J. Teuteberg, Kiran K. Khush
       
  • Variability in Donor Organ Offer Acceptance and Lung Transplantation
           Survival
    • Abstract: Publication date: Available online 21 January 2020Source: The Journal of Heart and Lung TransplantationAuthor(s): MS Mulvihill, HJ Lee, J Weber, AY Choi, ML Cox, BA Yerokun, MA Bishawi, J Klapper, M Kuchibhatla, MG Hartwig BackgroundLung transplantation (LTx) offers a survival benefit for patients with end-stage lung disease. When suitable donors are identified, centers must accept or decline the offer for a matched candidate on their waitlist. The degree to which variability in per-center offer acceptance practices impacts candidate survival is not established. The purpose of this study was to determine the degree of variability in per-center rates of LTX offer acceptance, and to ascertain the associated contribution to observed differences in per-center waitlist mortality.MethodsWe performed a retrospective cohort study of candidates waitlisted for LTx in the US using registry data. Logistic regression was fit to assess the relationship of offer acceptance with donor-, candidate-, and geographic factors. Listing center was evaluated as a fixed effect to determine the adjusted per-center acceptance rate. Competing risks analysis employing the Fine-Gray model was undertaken to establish the relationship between adjusted per-center acceptance and waitlist mortality.ResultsOf 15,847 unique organ offers, 4,735 (29.9%) were accepted for first-ranked candidates. After adjustment for important covariates, transplant centers varied markedly in acceptance rate (9% to 67%). Higher cumulative incidence of 1-year waitlist mortality was associated with lower acceptance rate. For every 10% increase in adjusted center acceptance rate, the risk of waitlist mortality decreased by 36.3% (subdistribution hazard ratio 0.637; 95% CI 0.592, 0.685).ConclusionsVariability in center-level behavior represents a modifiable risk factor for waitlist mortality in LTx. Further intervention is needed to standardize center-level offer acceptance practices and minimize waitlist mortality.
       
  • CLINICAL IMPLICATIONS OF IDIOPATHIC PULMONARY ARTERIAL HYPERTENSION
           PHENOTYPES DEFINED BY CLUSTER ANALYSIS
    • Abstract: Publication date: Available online 21 January 2020Source: The Journal of Heart and Lung TransplantationAuthor(s): Roberto Badagliacca, Franz Rischard, Silvia Papa, Saad Kubba, Rebecca Vanderpool, Jason X.-J. Yuan, Joe G.N. Garcia, Sophia Airhart, Roberto Poscia, Beatrice Pezzuto, Giovanna Manzi, Cristiano Miotti, Federico Luongo, Gianmarco Scoccia, Susanna Sciomer, Roberto Torre, Francesco Fedele, Carmine Dario VizzaABSTRACTBackgroundDespite advances in drug development, life expectancy in idiapathic pulmonary arterial hypertension (IPAH) remains unacceptable. Contemporary IPAH characterization is based on criteria that may not adequately capture disease heterogeneity and may be proposed as a possible explanation for why patient's outcome is still unfavorable.ObjectivesThe aim of the present study was to apply cluster analysis to improve phenotyping of IPAH patients and analyze long-term clinical outcome of derived clusters.MethodsTwo hundred-fifty two IPAH patients from two referral centers were evaluated with clinical, hemodynamic, echocardiographic assessment and cardiopulmonary exercise test. Patients were classified according to cluster analysis and followed for clinical worsening occurance.ResultsThe cluster analysis identified four IPAH phenotypes. Cluster-1 was characterized by young patients, mild PH, mild right ventricular (RV) dilation and high oxygen (O2) pulse; Cluster-2 by severe PH and RV dilation, and high O2 pulse; Cluster-3 by males, severe PH and RV dilation, and low O2 pulse. Cluster-4 patients were older and overweight, with mild PH and RV dilation, and low O2 pulse.After a mean follow-up of 995±623 days, 123 (48.8%) patients had clinical worsening. Cluster-1 patients presented the best prognosis, while Cluster-3 the highest rates of clinical worsening. Compared with Cluster-1, risk of clinical worsening ranged from 4.12 (C.I. 1.43-11.92; p=0.009) for Cluster-4 to 7.38 (C.I. 2.80-19.40) for Cluster-2 and 13.8 (C.I. 5.60 to 34.0; p=0.0001) for Cluster-3.ConclusionsCluster analysis of clinical variables identified 4 distinct phenotypes of IPAH. Our findings underscore the high degree of disease heterogeneity that exists within IPAH patients and the need for advanced clinical testing to define phenotypes to improve treatment strategy decision-making.CONDENSED ABSTRACTIdiapathic pulmonary arterial hypertension (IPAH) characterization is based on criteria that may not adequately capture disease heterogeneity. The aim of the present study was to apply cluster analysis to improve phenotyping of IPAH. Two hundred-fifty two IPAH patients were evaluated with clinical, hemodynamic, echocardiographic assessment and cardiopulmonary exercise test.Within the umbrella category of IPAH, it was the combination of mean pulmonary arterial pressure, right ventricular size and O2 pulse that further stratified patients into novel IPAH phenotypes that significantly associate with clinical worsening. These findings underscore the need for novel multi-dimensional IPAH phenotyping for improved patient care and trial quality.
       
  • Quantiferon-CMV Guided Virostatic Prophylaxis After Heart Transplantation
    • Abstract: Publication date: Available online 21 January 2020Source: The Journal of Heart and Lung TransplantationAuthor(s): Gregor Poglajen, Gregor Zemljič, Sabina Frljak, Andraž Cerar, Vesna Andročec, Tamara Božič, Mojca Bitenc, Renata Okrajšek, Miran Šebeštjen, Bojan Vrtovec
       
  • Ambrisentan in portopulmonary hypertension: A multicenter, open label
           trial
    • Abstract: Publication date: Available online 21 January 2020Source: The Journal of Heart and Lung TransplantationAuthor(s): Ioana R. Preston, Charles D. Burger, Sonja Bartolome, Zeenat Safdar, Michael Krowka, Namita Sood, Hubert J. Ford, Wejdan F. Battarjee, Murali M. Chakinala, Mardi Gomberg-Maitland, Nicholas S. HillABSTRACTBackgroundAmbrisentan is effective in Group 1 pulmonary arterial hypertension (PAH). Although portopulmonary hypertension (PoPH) is a subset of Group 1 PAH, few clinical trials testing PAH therapies enrolled PoPH patients. We aimed to evaluate the efficacy and safety of ambrisentan in PoPH.MethodsProspective, multicenter, open-label trial of treatment-naive PoPH patients with Child-Pugh class A/B receiving ambrisentan for 24 weeks, followed by long-term extension (24-28 weeks). The primary endpoints were change in pulmonary vascular resistance (PVR) and 6-minute walk distance (6MWD) at 24 weeks. Secondary endpoints included safety, World Health Organization functional class (WHO FC) and echocardiographic assessments.ResultsOf 31 patients, 23 finished 24 weeks and 19 finished the extension. PVR decreased significantly (mean±SD) (7.1 ± 5 vs. 3.8 ± 1.8 Wood units, p
       
  • Respiratory viral infection in lung-transplant induces exosomes that
           trigger chronic-rejection
    • Abstract: Publication date: Available online 21 January 2020Source: The Journal of Heart and Lung TransplantationAuthor(s): Muthukumar Gunasekaran, Ranjithkumar Ravichandran, Sandhya Bansal, Monal Sharma, Sudhir Perincheri, Francisco Rodriguez, Ramsey Hachem, Cynthia E. Fisher, Ajit P. Limaye, Ashraf Omar, Michael A. Smith, Ross M. Bremner, T Mohanakumar BackgroundRespiratory viral infections can increase the risk of chronic lung allograft dysfunction after lung transplantation, but the mechanisms are unknown. In this study, we determined whether symptomatic respiratory viral infections in post-lung transplantation induce circulating exosomes that contain lung-associated self-antigens, and to assess whether these exosomes activate immune responses to self-antigens.MethodsSera were collected from lung transplant recipients with symptomatic, lower and upper-tract respiratory viral infections and from non-symptomatic stable recipients. Exosomes were isolated via ultracentrifugation; purity was determined using sucrose cushion; presence of lung self-antigens, 20S proteasome, and viral antigens for rhinovirus, coronavirus, and respiratory syncytial virus were determined using immunoblot. Mice were immunized with circulating exosomes from each group and resulting differential immune responses and lung histology were analyzed.ResultsExosomes containing self-antigens, 20S proteasome, and viral antigens were detected at significantly higher levels (p
       
  • Information for Readers
    • Abstract: Publication date: February 2020Source: The Journal of Heart and Lung Transplantation, Volume 39, Issue 2Author(s):
       
  • ERRATUM
    • Abstract: Publication date: January 2020Source: The Journal of Heart and Lung Transplantation, Volume 39, Issue 1Author(s):
       
  • When good intentions turn bad: A need for course correction
    • Abstract: Publication date: January 2020Source: The Journal of Heart and Lung Transplantation, Volume 39, Issue 1Author(s): Hector O. Ventura, Howard Eisen
       
  • Information for Readers
    • Abstract: Publication date: January 2020Source: The Journal of Heart and Lung Transplantation, Volume 39, Issue 1Author(s):
       
  • Reply: Interpreting Multiple Analyses to Better Understand Cardiac
           Re-transplantation
    • Abstract: Publication date: Available online 29 December 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Robert JH Miller, Kiran K Khush, Francois Haddad
       
  • Ventricular Assist Device Bridge to Heart Transplantation in a Child with
           Homocystinuria
    • Abstract: Publication date: Available online 28 December 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Neha Bansal, Melissa P. Wasserstein, Aman M. Shah, Kimberly Beddows, William Jakobleff, Giles J Peek
       
  • Flow-targeted pediatric ex vivo heart perfusion in donation after
           circulatory death: A porcine model
    • Abstract: Publication date: Available online 5 December 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Junko Kobayashi, Shuhua Luo, Yohei Akazawa, Marlee Parker, Jian Wang, David Chiasson, Mark K. Friedberg, Christoph Haller, Osami HonjoBACKGROUNDThe optimal blood flow and pressure to perfuse pediatric hearts from donation after circulatory death (DCD) on the ex vivo perfusion system has not been elucidated. This study sought to investigate the optimal perfusion strategy for pediatric DCD hearts by using a juvenile porcine model comparing pressure- vs flow-targeted strategy.METHODSThe hearts of the juvenile DCD pigs were explanted, and the coronary arteries were perfused for 2 hours by the ex vivo heart perfusion system with 2 different perfusion strategies; pressure-targeted perfusion (target coronary perfusion pressure: 40 mm Hg, group A) and flow-targeted perfusion (target coronary perfusion flow: 10 ml/kg/min, group B). The working model heart perfusion was used to assess systolic and diastolic myocardial performance.RESULTSThe body weight, warm and cold ischemic time, and ex vivo perfusion time were comparable between the groups. In the working model, group B showed significantly preserved cardiac output (A: 70.5 ± 15.3 ml/kg/min vs B: 113.8 ± 15.0 ml/kg/min, p < 0.01), stroke volume (A: 0.4 ± 0.1 ml/kg vs B: 0.7 ± 0.1 ml/kg, p < 0.01), and ejection fraction (A: 18.8% ± 5.9% vs B: 35.0% ± 10.6%, p < 0.01). E/e’ and Tei index were also significantly preserved in group B. The percentage gain of heart weight after ex vivo (net increase of the heart weight divided by heart weight at baseline) was significantly smaller in group B (A: 20.0% ± 5.3% vs B: 11.6% ± 5.0%, p < 0.05). Troponin-I, myocardial hemorrhage, oxidative stress markers; myeloperoxidase and 8-hydroxy-2’-deoxyguanosine were also significantly lower after ex vivo perfusion in group B (p < 0.05).CONCLUSIONSThe tightly controlled flow-targeted myocardial perfusion strategy for DCD donor hearts achieved better myocardial performance by causing less myocardial edema and limiting myocardial reperfusion injury.
       
  • Pulmonary vascular imaging characteristics after pulmonary endarterectomy
           for chronic thromboembolic pulmonary hypertension
    • Abstract: Publication date: Available online 5 December 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Natalia J. Braams, Dieuwertje Ruigrok, Monique G.M. Schokker, Lina Padervinskiene, Frances S. de Man, J. Tim Marcus, Rutger J. Lely, Marcel A.M. Beijk, Frederikus A. Klok, Menno V. Huisman, Esther J. Nossent, Anton Vonk Noordegraaf, Petr Symersky, Harm Jan Bogaard, Lilian J. MeijboomBACKGROUNDBetween 16% and 51% of patients with chronic thromboembolic pulmonary hypertension will have residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). Whether residual PH is related to remaining (sub-)segmental macrovascular lesions or to microvascular disease is unknown. New imaging techniques can provide detailed information about (sub-)segmental pulmonary arteries and parenchymal perfusion. The aim of this study was to describe the prevalence after PEA of remaining (sub-)segmental vascular lesions on electrocardiogram-gated computed tomography pulmonary angiography (CTPA) and parenchymal hypoperfusion on magnetic resonance imaging (MRI) and to relate these imaging abnormalities to the presence or absence of residual PH after PEA.METHODSIn a prospective cohort of patients with operable chronic thromboembolic pulmonary hypertension, hemodynamics, CTPA, and lung perfusion MRI were performed before and 6 months after PEA. The percentage of (sub-)segmental vascular lesions was calculated on CTPA and parenchymal hypoperfusion on lung perfusion MRI.RESULTSPEA led to significant improvements in hemodynamics and a reduction of imaging abnormalities. Residual PH was present in 45% of patients after PEA, whereas remaining (sub-)segmental vascular lesions and parenchymal hypoperfusion were present in 20% and 21% of the pulmonary vasculature, respectively. Patients with and without residual PH after PEA had similar percentages of remaining (sub-)segmental vascular lesions (25% ± 14% vs 17% ± 15%; p = 0.16) and similar degrees of parenchymal hypoperfusion (20% ± 7% vs 19% ± 6%; p = 0.63).CONCLUSIONSAfter successful PEA, advanced imaging shows that around 20% of the pulmonary vasculature remains abnormal, independent of the presence of residual PH. This may suggest that microvascular disease, rather than residual macrovascular lesions, plays a prominent role in residual PH after PEA.
       
  • Donor Fraction Cell-Free DNA and Rejection in Adult and Pediatric Heart
           Transplantation
    • Abstract: Publication date: Available online 29 November 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Marc E Richmond, Steven D Zangwill, Steven J Kindel, Shriprasad R Deshpande, Jacob N Schroder, David P Bichell, Kenneth R Knecht, William T Mahle, Mark A Wigger, Nunzio A Gaglianello, Elfriede Pahl, Pippa M Simpson, Mahua Dasgupta, Paula E North, Mats Hidestrand, Aoy Tomita-Mitchell, Michael E Mitchell PurposeEndomyocardial biopsy (EMB) is the current standard for rejection surveillance in heart transplant recipients. Quantification of donor-specific cell-free DNA (cfDNA) may be an appropriate biomarker for non-invasive rejection surveillance. A multi-center prospective blinded study (DNA-based Transplant Rejection Test, DTRT) investigated the value of donor fraction (DF), defined as the ratio of cfDNA specific to the transplanted organ to total amount of cfDNA present in a blood sample.Methods241 heart transplant patients were recruited from seven centers. Age at transplant ranged from 8 days to 73 years, with 146 subjects
       
  • Reverse transcriptase multiplex ligation-dependent probe amplificatioN IN
           ENDOMYOCARDIAL BIOPSIES for the diagnosis of cardiac allograft rejection
    • Abstract: Publication date: Available online 26 November 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Nicolas Adam, Guillaume Coutance, Pierre-Julien Viailly, Fanny Drieux, Philippe Ruminy, Ahmad Abdel Sater, Claire Toquet, Philippe Rouvier, Arnaud François, Marie-Pierre Chenard, Eric Epailly, Romain Guillemain, Sabine Pattier, Arnaud Gay, Shaida Varnous, Jean-Luc Taupin, Marion Rabant, Alexandre Loupy, Patrick Bruneval, Jean Paul Duong Van HuyenABSTRACTBackgroundMolecular biology has emerged as a potential companion to histology for the diagnosis of rejection after heart transplantation. Reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) is a technique of targeted gene expression analysis suitable for formalin-fixed paraffin-embedded (FFPE) biopsies. Our aim was to assess RT-MLPA for the diagnosis of allograft rejection in heart transplantation.MethodsWe performed a cross-sectional, case-control, multicenter study. After selection of a 14-transcript panel (endothelial burden, Natural-Killer cells, interferon-γ pathway, effector T-cells and antigen presentation), RT-MLPA was applied to 183 FFPE endomyocardial biopsies (EMB), randomized into a training (n=113) and a validation (n=70) series. A two-step class prediction analysis was developed (Linear prediction score - LPS1: rejection versus non-rejection; LPS2: antibody-mediated rejection -AMR- versus acute cellular rejection -ACR). A study of the agreement between pathology and RT-MLPA was performed.ResultsOverall, 48 ACR, 82 AMR, five mixed-rejection, and 48 non-rejection EMBs were analyzed. Three molecular clusters were delineated by unsupervised hierarchical analysis (molecular non-rejection, ACR and AMR). AMR was characterized by high expression of CCL4, GNLY, FCGR3, CXCL11 and ACR by high expression of CCL18 and ADAMdec. RT-MLPA and histopathology agreed in the final diagnosis in 82.2%, 67.7%, and 76.8% of the EMB in the test, validation and overall cohort, respectively. Disagreement cases were more common in the case of histological low-grade rejection and early post-transplant EMB.ConclusionRT-MLPA is a suitable technique for targeted gene expression analysis on FFPE EMB with a good overall agreement with the histological diagnosis of heart allograft rejection.
       
  • Outcomes Based on Blood Pressure in Patients on Continuous Flow LVAD
           Support: An INTERMACS analysis
    • Abstract: Publication date: Available online 26 November 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): J. Cowger, P. Shah, F. Pagani, G. Grafton, J. Stulak, T. Chamogeorgakis, D. Lanfear, H. Nemeh, S. PinneyBackgroundAn optimal blood pressure (BP) range to mitigate morbidity and mortality on left ventricular assist device (LVAD) support has not been clearly defined.MethodsAverage Doppler opening pressure, mean arterial pressure (MAP), and/or systolic blood pressure (SBP) were calculated in operative survivors (n=16155) of LVAD support in INTERMACS. BP distributions were used to group patients: low (BP 95th percentile). Associations between BP and adverse events were evaluated using Cox Regression (Hazard ratio (HR), 95% confidence interval).ResultsThe median MAP, Doppler, and SBPs (mmHg) during CFLVAD support were 84 [77, 90], 85 [80, 92], and 99 [90,107] mmHg. BP had a bimodal risk association with survival. At 3 years, survival was 58±1.8% in those with low MAPs (≤75 mmHg) vs. 70±0.9%, 71±1.5%, and 63±3.0% in the those with normal, high, or very high average MAPs. Patients with chronically low MAPs (≤75 mmHg), Dopplers (≤80 mmHg) and SBPs (100 mmHg, Dopplers ≥105 mmHg, and SBPs ≥120 mmHg had 17-20% higher adjusted hazards of death than those with normal pressures (p75 mmHg and
       
  • T follicular helper and memory cell responses and the mTOR pathway in
           murine heart transplantation
    • Abstract: Publication date: Available online 26 November 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Aini Xie, Hui Yan, Jinfei Fu, Adam He, Xiang Xiao, Xian C. Li, Wenhao ChenABSTRACTBACKGROUNDMammalian target of rapamycin (mTOR) inhibitors are valuable immunosuppressants in clinical transplantation, but mTOR regulation of allogeneic T cell responses is not fully understood. Here, we investigated the effects of T cell-specific mTOR deletion on allogeneic T cell responses and heart transplant survival.METHODSWild type C57BL/6, Mtorfl/flCd4-Cre, Stat3fl/flCd4-Cre, and Mtorfl/flStat3fl/flCd4-Cre mice were transplanted with BALB/c heart allografts, with or without BALB/c skin-sensitization. Graft survival and histology, as well as T cell frequencies and phenotypes, were evaluated after transplantation.RESULTSIn the absence of donor skin-sensitization, long-term heart allograft survival was achieved in Mtorfl/flCd4-Cre recipients, which was associated with significantly decreased frequencies of CD62L–CD44+ effector T cells and BCL-6+CXCR5+ T follicular helper (Tfh) cells in the periphery. Long-term heart allograft survival was also achieved in donor skin-sensitized Mtorfl/flStat3fl/flCd4-Cre mice, whereas heart allograft survival was prolonged in donor skin-sensitized Mtorfl/flCd4-Cre and Stat3fl/flCd4-Cre mice.CONCLUSIONSmTOR is required for Tfh cell response in murine heart transplantation. T cell-specific deletion of both mTOR and Stat3 abrogates memory response to heart transplants. These findings help us to better understand the molecular mechanisms underlying T cell immunity to transplanted organs.
       
  • Donor Name Visibility in DonorNet
    • Abstract: Publication date: Available online 26 November 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Katherine C. Michelis, Sonia Garg, Mark H. Drazner
       
  • Pathological Insights Into Persistent Mitral Regurgitation Following
           Continuous Flow Left Ventricular Assist Device Implantation
    • Abstract: Publication date: Available online 26 November 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Indranee Rajapreyar, J. Eduardo Rame, Paul Fiorilli, Salpy V. Pamboukian, Charles W. Hoopes, Scott C. Silvestry, Francis D. Pagani, Keshava Rajagopal
       
  • USE OF CT-SCAN SCORE AND VOLUME MEASURES TO EARLY IDENTIFY RESTRICTIVE
           ALLOGRAFT SYNDROME IN SINGLE-LUNG TRANSPLANT RECIPIENTS
    • Abstract: Publication date: Available online 25 November 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Q Philippot, MP Debray, René Bun, J Frija-Masson, V Bunel, L Morer, A Roux, C Picard, G Jebrak, G Dauriat, Y Castier, A Cazes, H Mal, JL Taupin, C Couffignal, O BrugièreABSTRACTBackgroundRestrictive allograft syndrome (RAS) after lung transplantation (LTx) is associated with the poorer graft survival in patients with chronic lung allograft dysfunction (CLAD). Nevertheless, its diagnostic criteria remain not well defined after single-LTx (SLTx). Hence, we studied an SLTx cohort with CLAD to investigate the utility of both CT-score/volume measures and functional spirometric criteria for early identifying RAS in this population.MethodsWe included 51 SLTx patients (17 RAS, 17 bronchiolitis obliterans syndrome [BOS], 17 stable condition). Criteria for RAS diagnosis in SLTx included FVC
       
  • PLASMA CD5L AND NON-INVASIVE DIAGNOSIS OF ACUTE HEART REJECTION
    • Abstract: Publication date: Available online 21 November 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Estefanía Tarazón, Nerea Corbacho-Alonso, María G. Barderas, Carolina Gil-Cayuela, María García Manzanares, Sandra Feijóo-Badín, Francisca Lago, José Ramón González-Juanatey, Luis Martínez-Dolz, Manuel Portolés, Esther Roselló-LletíABSTRACTBackgroundAcute rejection is one of the most important direct contributors of mortality after heart transplantation. Advances in the development of novel non-invasive approaches for the early identification of allograft rejection are necessary. We conducted a non-targeted proteome characterization focused on identifying multiple plasmatic protein differences to evaluate their diagnostic accuracy for rejection episodes.MethodsWe included consecutive plasma samples from transplant recipients undergoing routine endomyocardial biopsies. A LC-MS/MS analysis using isobaric tags (TMT 10-plex) was performed and concentrations of CD5L were validated using a specific sandwich enzyme-linked immunosorbent assay.ResultsA total of 17 altered proteins were identified as potential markers for detecting heart transplant rejection, most involved in inflammation and immunity. CD5L, apoptosis inhibitor expressed by macrophages, showed the best results in the proteomic analysis (n=30). We confirm this finding in a larger patient cohort (n=218), obtaining a great diagnostic capacity for clinically relevant rejection (≥Grade 2R AUC=0.892, p
       
  • Influence of azithromycin and allograft rejection on the post-lung
           transplant microbiota
    • Abstract: Publication date: Available online 21 November 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Christopher D Spence, Bart Vanaudenaerde, Gísli G Einarsson, John Mcdonough, Andrew J Lee, Elinor Johnston, Geert M Verleden, J Stuart Elborn, Lieven J Dupont, Anke Van Herck, Deirdre F Gilpin, Robin Vos, Michael M Tunney, Stijn E VerledenABSTRACTBackgroundAlterations in the lung microbiota may drive disease development and progression in patients with chronic respiratory diseases. Following lung transplantation (LTx), azithromycin is used to both treat and prevent chronic lung allograft dysfunction (CLAD). The objective of this study was to determine the association between azithromycin use, CLAD, acute rejection, airway inflammation and bacterial microbiota composition and structure after LTx.MethodsBronchoalveolar lavage (BAL) samples (n=219) from 69 LTx recipients (azithromycin, n=32; placebo, n=37) from a previously conducted randomized placebo-controlled trial with azithromycin were analysed. Samples were collected at discharge, 1 and 2 years following randomization and at CLAD diagnosis. Bacterial microbial community composition and structure was determined using 16S rRNA gene sequencing and associated with clinically important variables.ResultsAt discharge and following 1 and 2 years of azithromycin therapy, no clear differences in microbial community composition or overall diversity were observed. Moreover, no changes in microbiota composition were observed in CLAD phenotypes. However, acute rejection was associated with a reduction in community diversity (p = 0.0009). Significant correlations were observed between microbiota composition, overall diversity and levels of inflammatory cytokines in BAL, particularly CXCL8.ConclusionsChronic azithromycin usage did not disturb the bacterial microbiota. However, acute rejection episodes were associated with bacterial dysbiosis.
       
  • Quality of Life and Treatment Preference for VAD therapy in Ambulatory
           Advanced Heart Failure: A Report from the REVIVAL Study
    • Abstract: Publication date: Available online 20 November 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Josef Stehlik, Maria Mountis, Donald Haas, Maryse Palardy, Amrut V. Ambardekar, Jerry D. Estep, Gregory Ewald, Stuart D. Russell, Shawn Robinson, Ulrich Jorde, Wendy C. Taddei-Peters, Neal Jeffries, Blair Richards, Shokoufeh Khalatbari, Catherine Spino, J. Timothy Baldwin, Douglas Mann, Garrick C. Stewart, Keith D. Aaronson, for the REVIVAL Investigators. IntroductionThe Registry Evaluation of Vital Information for VADs in Ambulatory Life (REVIVAL) study is a prospective multicenter cohort of 400 ambulatory patients with advanced chronic systolic heart failure (HF). The aim of REVIVAL is to better understand disease trajectory and optimal timing of advanced HF therapies. We examined patient health-related quality of life (HRQOL) data collected at enrollment, and their association with patient treatment preferences for ventricular assist device (VAD) placement.MethodsBaseline assessment of HRQOL included Kansas City Cardiomyopathy Questionnaire (KCCQ) and EuroQol EQ-5D-3L Visual Analog Scale (VAS), along with patient self-assessment of remaining life (PSARL). Descriptive statistics were used to present baseline HRQOL data and Spearman correlation test to assess the association between KCCQ, VAS and VAD treatment preference with patient clinical characteristics of interest.ResultsThe median age was 60 years, 75% were male, and the median left ventricular ejection fraction was 20%. The median [25th percentile, 75th percentile], baseline KCCQ summary score was 64 [48,78], VAS score 65 [50,75] and PSARL 7 years [5,10]. There were statistically significant associations of baseline KCCQ and VAS with NYHA Class and INTERMACS profile (p
       
  • Propensity score matching and proportional hazard models: Which is best to
           understand heart re-transplantation outcomes'
    • Abstract: Publication date: Available online 20 November 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Dmitry Tumin, Deipanjan Nandi, Don Hayes
       
  • An Early Investigation of Outcomes with the New 2018 Donor Heart
           Allocation System in the United States
    • Abstract: Publication date: Available online 20 November 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Rebecca Cogswell, Ranjit John, Jerry Estep, Sue Duval, Ryan J. Tedford, Francis D Pagani, Cindy M. Martin, Mandeep R. Mehra
       
  • Pulmonary Arterial Hypertension In the Modern Era: The Intersection of
           Genotype and Phenotype
    • Abstract: Publication date: Available online 9 November 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Nicole F. Ruopp, Bradley A. Maron
       
  • DIFFERENCES IN HEALTH-RELATED QUALITY OF LIFE BY IMPLANT STRATEGY:
           ANALYSES FROM INTERMACS
    • Abstract: Publication date: Available online 6 November 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Connie White-Williams, Pariya L. Fazeli, James K. Kirklin, Salpy V. Pamboukian, Kathleen L. Grady BackgroundMid-term change in health-related quality of life (HRQOL) by left ventricular assist device (LVAD) implant strategy is unknown. The purpose of this study was to examine HRQOL by pre-operative implant strategy from before to 2 years after surgery.MethodsAdult patients in the Interagency Registry for Mechanically Assisted Circulatory Support were stratified into three groups based on pre-implant device strategy: destination therapy (DT) (n=2901), bridge to transplant (BTT) (n=2209), and bridge to candidacy (BTC) (n=3076). HRQOL data were collected before and 2 years after surgery using the generic EQ-5D-3L survey and heart failure-specific KCCQ-12. Statistical analyses included chi square tests, analysis of variance, paired t-tests, and general linear random effects models.ResultsBetween 04/01/08 and 06/30/13, 4422 patients and 1660 patients (majority males and ≥ 50 years) who received primary continuous flow LVADs completed baseline EQ-5D-3L and KCCQ-12 questionnaires, respectively, while 1615 and 1408 patients completed EQ-5D-3L and KCCQ-12 questionnaires at 2 years, respectively. While paired t-tests and general linear random effects models showed that both heart failure-specific and generic HRQOL improved for all groups across time (p-values
       
  • TREATMENT OF LIFE-THREATENING PSEUDOMONAS AERUGINOSA INFECTION BY PHERESIS
           OF INHIBITORY ANTIBODIES
    • Abstract: Publication date: Available online 21 October 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Chandima Divithotawela, Amy Pham, Emma L. Ledger, Peter Hopkins, Timothy J. Wells, Daniel Chambers
       
  • Acquired Von Willebrand Syndrome and Left Ventricular Assist Devices
    • Abstract: Publication date: Available online 10 October 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Ulrich Geisen, Friedhelm Beyersdorf, Barbara Zieger
       
  • Reply to “Geisen et al. JHLT-D-19-00585R2” Acquired Von Willebrand
           Syndrome and Left Ventricular Assist Devices
    • Abstract: Publication date: Available online 10 October 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Jean M Connors, Mandeep R. Mehra
       
  • Reduced Flow ex vivo Lung Perfusion to Rehabilitate Donation After Cardiac
           Death Lungs
    • Abstract: Publication date: Available online 18 September 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Jared P. Beller, Matthew R. Byler, Dustin T. Money, William Z. Chancellor, Aimee Zhang, Yunge Zhou, Mark H. Stoler, Adishesh K. Narahari, Alexander Shannon, J Hunter Mehaffey, Curtis G. Tribble, Victor E. Laubach, Irving L. Kron, Mark E. RoeserBackgroundCurrent ex vivo lung perfusion (EVLP) protocols aim to achieve perfusion flows of 40% of cardiac output or more. We hypothesized that a lower target flow rate during EVLP would improve graft function and decrease inflammation of donation after circulatory death (DCD) lungs.MethodsA porcine DCD and EVLP model was utilized. Two groups (n=4/group) of DCD lungs were randomized to target EVLP flows of 40% (High Flow) or 20% (Low Flow) predicted cardiac output based on 100mL/min/kg. At the completion of 4 hours of normothermic EVLP using Steen solution, left lung transplantation was performed, and lungs were monitored during 4 hours of reperfusion.ResultsAfter transplant, left lung-specific pulmonary vein PO2 was significantly higher in the Low Flow group at 3 and 4 hours of reperfusion (3-hour: 496.0±87.7 vs. 252.7±166.0 mmHg, p=0.017; 4-hour: 429.7±93.6 vs. 231.5±178 mmHg, p=0.048). Compliance was significantly improved at 1 hour of reperfusion (20.8±9.4 vs. 10.2±3.5 ml/cm H2O, p=0.022) and throughout all subsequent time points in the Low Flow group. After reperfusion, lung wet-to-dry weight ratio (7.1±0.7 vs. 8.8±1.1, p=0.040) and IL-1β expression (927±300 vs. 2070±874 pg/ng protein, p=0.048) were significantly reduced in the Low Flow group.ConclusionsEVLP of DCD lungs with low flow targets of 20% predicted cardiac output improves lung function, reduces edema and attenuates inflammation after transplant. Therefore, EVLP for lung rehabilitation should use reduced flow rates of 20% predicted cardiac output.
       
  • Registry Evaluation of Vital Information for VADs in Ambulatory Life
           (REVIVAL): Rationale, Design, Baseline Characteristics and Inclusion
           Criteria Performance
    • Abstract: Publication date: Available online 14 September 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Keith D Aaronson, Garrick C Stewart, Francis D Pagani, Lynne W Stevenson, Maryse Palardy, Dennis M McNamara, Donna M Mancini, Kathleen Grady, John Gorcsan, Robert Kormos, Neal Jeffries, Wendy C Taddei-Peters, Blair Richards, Shokoufeh Khalatbari, Cathie Spino, J Timothy Baldwin, Douglas L Mann, for the REVIVAL Investigators IntroductionImproved understanding of the clinical course of ambulatory advanced chronic systolic heart failure may improve the provision of appropriate care and is central to the design of clinical trials in this population.MethodsTwenty-one implanting VAD centers enrolled 400 subjects in REVIVAL,  a prospective, observational study in ambulatory, chronic advanced systolic heart failure (HF), designed to identify a cohort with an approximately 25% 1-year risk of the primary composite outcome of death, urgent transplant or durable MCS. Inclusion criteria utilized only information collected during routine clinical care. Exclusion criteria identified patients with contraindications to VAD. Study inclusion required at least 1 of 10 high-risk criteria derived from established hospitalization and non-hospitalization markers of increased mortality risk . We evaluated the test performance characteristics of the high-risk criteria.ResultsData on 373 subjects evaluable for the primary composite outcome at the 1-year visit are presented. Baseline data were consistent with a less advanced cohort than MedaMACS or ROADMAP. Freedom from the primary composite outcome was 75.9%. Non-hospitalization inclusion criteria identified 89% of patients with events.ConclusionsUsing routinely obtained clinical information for enrollment, REVIVAL successfully recruited an ambulatory chronic systolic heart failure cohort with an approximately 25% annual risk of the primary composite outcome. Information from this registry will be relevant to the planning of future trials of earlier VAD use and of other interventions in this population.
       
  • First+Human+Implantation+of+A+Miniaturized+Axial+Flow+Ventricular+Assist+Device+in+a+Child+with+End-Stage+Heart+Failure&rft.title=Journal+of+Heart+and+Lung+Transplantation&rft.issn=1053-2498&rft.date=&rft.volume=">First Human Implantation of A Miniaturized Axial Flow Ventricular Assist
           Device in a Child with End-Stage Heart Failure
    • Abstract: Publication date: Available online 11 September 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Antonio Amodeo, Sergio Filippelli, Gianluigi Perri, Roberta Iacobelli, Rachele Adorisio, Francesca Iodice, Alessandra Rizza, M. Patricia Massicotte, J. Timothy Baldwin, Christopher S.D. Almond
       
  • A DONOR PaO2/FiO2 LESS THAN 300 MMHG DOES NOT DETERMINE GRAFT FUNCTION OR
           SURVIVAL AFTER LUNG TRANSPLANTATION
    • Abstract: Publication date: Available online 2 September 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Helen Whitford, Christina E. Kure, Aimee Henriksen, Jamie Hobson, Greg I. Snell, Bronwyn J. Levvey, Silvana F. Marasco, Julian H. Gooi, Adam Zimmet, Justin Negri, Adrian Pick, Mark Buckland, Trevor Williams, Glenn Westall, Miranda A. Paraskeva, Catherine Martin, David C. McGiffinABSTRACTBackgroundA donor arterial PO2/FiO2 (P/F ratio) less than the 300 threshold would frequently result in either exclusion of the donor or placement of the lungs on ex-vivo lung perfusion (EVLP). The aim was to investigate the veracity of the P/F ratio threshold of 300 for donor lung acceptability.MethodsIn 93 brain dead lung donors, arterial blood gases were drawn in the intensive care unit (ICU) just prior to procurement and each of the four donor pulmonary veins in the operating room (OR). No donor lungs were rejected for transplantation based on the last ICU or OR P/F ratio and EVLP was not used. Recipients were followed up 6 and 12 months following transplantation.ResultsThere were 93 recipients of bilateral lung transplantation. An arterial P/F ratio of less than 300 was largely driven by a low P/F ratio in the lower lobes. There were no differences between recipients receiving donor lungs where the ICU P/F ratio was less than 300 compared to greater than or equal to 300 in time to extubation, grade of primary graft dysfunction, pulmonary function at 6 and 12 months, and 12-month survival.ConclusionsFrom this study:1. If a donor P/F threshold of 300 was adhered to, 36% would have been rejected.2. The donor P/F ratio threshold of 300 is excessively conservative and results in wastage of donor lungs and the application of unnecessary EVLP.
       
  • Poor Outcomes in Carriers of the RNF213 Variant (p.Arg4810Lys) with
           Pulmonary Arterial Hypertension
    • Abstract: Publication date: Available online 2 September 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Takahiro Hiraide, Masaharu Kataoka, Hisato Suzuki, Yuki Aimi, Tomohiro Chiba, Sarasa Isobe, Yoshinori Katsumata, Shinichi Goto, Kohsuke Kanekura, Yoshitake Yamada, Hidenori Moriyama, Hiroki Kitakata, Jin Endo, Shinsuke Yuasa, Yasumichi Arai, Nobuyoshi Hirose, Toru Satoh, Yoji Hakamata, Motoaki Sano, Shinobu Gamou BackgroundA variant of c.14429G>A (p.Arg4810Lys, rs112735431) in the ring finger protein 213 gene (RNF213; NM_001256071.2) has been recently identified as a risk allele for pulmonary arterial hypertension (PAH). PAH can be added as a new member of RNF213-associated vascular diseases, which include Moyamoya disease and peripheral pulmonary stenosis. Our aim was to identify the clinical features and outcomes of PAH patients with this variant.MethodsWhole-exome sequencing was performed in 139 idiopathic (or possibly heritable) PAH patients.ResultsThe RNF213 p.Arg4810Lys variant was identified in a heterozygous state in 11 patients (7.9%). Time-course changes in hemodynamics after combination therapy in the patients with the RNF213 p.Arg4810Lys variant were significantly poorer compared with those carrying the bone morphogenic protein receptor type 2 (BMPR2) mutation (n = 36) (comparison of changes in mean pulmonary arterial pressure, p = 0.007). The event-free rate of death or lung transplantation was significantly poorer in RNF213 p.Arg4810Lys variant carriers than in BMPR2 mutation carriers (5-year event-free rate since the introduction of prostaglandin I2 infusion, 0% vs. 93%, respectively; p < 0.001).ConclusionsIdiopathic PAH patients with the RNF213 p.Arg4810Lys variant are associated with poor clinical outcomes even in recent times. Earlier consideration of lung transplantation might be required for RNF213 p.Arg4810Lys variant carriers developing PAH. Documentation of the RNF213 p.Arg4810Lys variant, as well as already known pathogenic genes, such as BMPR2, can provide clinically relevant information for therapeutic strategies, leading to a personalized approach for the treatment of PAH.
       
  • INTERMACS Profiles and Outcomes of Ambulatory Advanced Heart Failure
           Patients: A Report from the REVIVAL Registry
    • Abstract: Publication date: Available online 28 August 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Michelle M Kittleson, Palak Shah, Anuradha Lala, Rhondalyn C McLean, Salpy Pamboukian, Douglas A Horstmanshof, Jennifer Thibodeau, Keyur Shah, Jeffrey Teuteberg, Nisha A Gilotra, Wendy C Taddei-Peters, Thomas M Cascino, Blair Richards, Shokoufeh Khalatbari, Neal Jeffries, Lynne W Stevenson, Douglas Mann, Keith D Aaronson, Garrick C Stewart, for the REVIVAL Investigators IntroductionAmbulatory patients with advanced heart failure are often considered for advanced therapies, including durable mechanical circulatory support (MCS). The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profiles are a commonly used descriptor of disease severity in patients receiving MCS devices, but their role in defining the prognosis of ambulatory patients is less well-established, especially for Profiles 6 and 7.MethodsREVIVAL is a prospective, observational study of 400 outpatients from 21 MCS/cardiac transplant centers. Eligible patients had NYHA class II-IV symptoms despite optimal medical and electrical therapies with a recent heart failure hospitalization, heart transplant listing, or evidence of high neurohormonal activation.ResultsThe cohort included 33 (8%) INTERMACS Profile 4, 83 (21%) Profile 5, 155 (39%) Profile 6, and 129 (32%) Profile 7. Across INTERMACS Profiles, there were no differences in age, gender, ejection fraction, blood pressure, or use of guideline-directed medical therapy. A lower INTERMACS Profile was associated with more hospitalizations, greater frailty and more impaired functional capacity and quality of life. The composite endpoint of death, durable MCS, or urgent transplant at 12 months occurred in 39%, 27%, 24%, and 14% subjects with INTERMACS Profiles 4, 5, 6, and 7, respectively (p = 0.004).ConclusionsAmong ambulatory patients with advanced heart failure, a lower INTERMACS Profile was associated with a greater burden of heart failure across multiple dimensions and a higher composite risk of durable MCS, urgent transplant, or death. These Profiles may assist in risk assessment and triaging ambulatory patients to advanced therapies.
       
  • Endothelin-1, cardiac morphology, and heart failure: The MESA Angiogenesis
           Study
    • Abstract: Publication date: Available online 10 August 2019Source: The Journal of Heart and Lung TransplantationAuthor(s): Peter J. Leary, Nancy S. Jenny, David A. Bluemke, Steven M. Kawut, Richard A. Kronmal, Joao A. Lima, Bradley A. Maron, David D. Ralph, Samuel G. Rayner, John J. Ryan, Zachary L. Steinberg, Karen D. Hinckley Stukovsky, Ryan J. Tedford BackgroundCirculating levels of endothelin-1 (ET1) are elevated in heart failure and predict poor prognosis; however, it is not clear whether ET1 elevation is an adaptive response, maladaptive response, or an epiphenomenon of heart failure. In the current study, we evaluated relationships between ET1, cardiac morphology, and incident heart failure or cardiovascular death in participants with no evidence of clinical cardiovascular disease at the time ET1 was measured.Methods and ResultsET1 was measured 1,361 participants in the Multi-Ethnic Study of Atherosclerosis Angiogenesis Sub-Study. As suggested by linear regression, participants with lower circulating ET1 levels tended to be older, non-white, more likely to have smoked heavily, and less likely to report intentional exercise. Participants with higher ET1 levels had smaller left ventricular end-diastolic volumes (8.9 mL smaller per log increase in ET1, 95% CI 17.1 to 0.7, p=0.03) with an increased left ventricular ejection fraction (2.8% per log increase in ET1, 95% CI 0.5 to 5.2%, p=0.02). As suggested by Cox Proportional Hazards estimates, participants with higher ET1 levels had a lower risk for the composite outcome of heart failure or cardiovascular death in models that were unadjusted or had limited adjustment (p=0.03 and 0.05 respectively). Lower risk for heart failure could not be clearly shown in a model including health behaviors.ConclusionsThese results suggest, but do not confirm that elevated levels of circulating ET1 are associated with a more favorable cardiac phenotype. The relationship between ET1 and outcomes was not fully independent of one or more covariates.
       
 
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