TY  - JOUR
AB  - BACKGROUND: A diagnosis of idiopathic pulmonary arterial hypertension (IPAH) is frequently made in elderly patients who present with comorbidities, especially hypertension, coronary heart disease, diabetes mellitus, and obesity. It is unknown to what extent the presence of these comorbidities affects the response to PAH therapies and whether risk stratification predicts outcome in patients with comorbidities. METHODS: We assessed the database of COMPERA, a European pulmonary hypertension registry, to determine changes after initiation of PAH therapy in WHO functional class (FC), 6-minute walking distance (6MWD), brain natriuretic peptide (BNP) or N-terminal fragment of probrain natriuretic peptide (NT-pro-BNP), and mortality risk assessed by a 4-strata model in patients with IPAH and no comorbidities, 1-2 comorbidities and 3-4 comorbidities. RESULTS: The analysis was based on 1,120 IPAH patients (n = 208 [19%] without comorbidities, n = 641 [57%] with 1-2 comorbidities, and n = 271 [24%] with 3-4 comorbidities). Improvements in FC, 6MWD, BNP/NT-pro-BNP, and mortality risk from baseline to first follow-up were significantly larger in patients with no comorbidities than in patients with comorbidities, while they were not significantly different in patients with 1-2 and 3-4 comorbidities. The 4-strata risk tool predicted survival in patients without comorbidities as well as in patients with 1-2 or 3-4 comorbidities. CONCLUSIONS: Our data suggest that patients with IPAH and comorbidities benefit from PAH medication with improvements in FC, 6MWD, BNP/NT-pro-BNP, and mortality risk, albeit to a lesser extent than patients without comorbidities. The 4-strata risk tool predicted outcome in patients with IPAH irrespective of the presence of comorbidities.
AU  - Rosenkranz, S.*
AU  - Pausch, C.*
AU  - Coghlan, J.G.*
AU  - Huscher, D.*
AU  - Pittrow, D.*
AU  - Grünig, E.*
AU  - Staehler, G.*
AU  - Vizza, C.D.*
AU  - Gall, H.*
AU  - Distler, O.*
AU  - Delcroix, M.*
AU  - Ghofrani, H.A.*
AU  - Ewert, R.*
AU  - Kabitz, H.J.*
AU  - Skowasch, D.*
AU  - Behr, J.
AU  - Milger, K.*
AU  - Halank, M.*
AU  - Wilkens, H.*
AU  - Seyfarth, H.J.*
AU  - Held, M.*
AU  - Scelsi, L.*
AU  - Neurohr, C.*
AU  - Vonk-Noordegraaf, A.*
AU  - Ulrich, S.*
AU  - Klose, H.*
AU  - Claussen, M.*
AU  - Eisenmann, S.*
AU  - Schmidt, K.H.*
AU  - Remppis, B.A.*
AU  - Skride, A.*
AU  - Jureviciene, E.*
AU  - Gumbiene, L.*
AU  - Miliauskas, S.*
AU  - Löffler-Ragg, J.*
AU  - Lange, T.J.*
AU  - Olsson, K.M.*
AU  - Hoeper, M.M.*
AU  - Opitz, C.*
C1  - 70290
C2  - 55152
SP  - 102-114
TI  - Risk stratification and response to therapy in patients with pulmonary arterial hypertension and comorbidities: A COMPERA analysis.
JO  - J. Heart Lung Transpl.
VL  - 42
IS  - 1
PY  - 2023
SN  - 1053-2498
ER  - 

TY  - JOUR
AU  - Liu, H.*
AU  - Hollauer, C.
AU  - Hagl, C.*
AU  - Michel, S.*
AU  - Yildirim, A.Ö.
AU  - Dashkevich, A.*
C1  - 64961
C2  - 51992
SP  - S311-S311
TI  - Prolonged cold ischemia and indirect alloimmunity are fundamental for the development of chronic lung allograft dysfunction.
JO  - J. Heart Lung Transpl.
VL  - 41
IS  - 4
PY  - 2022
SN  - 1053-2498
ER  - 

TY  - JOUR
AB  - BACKGROUND: Riociguat in Patients with Symptomatic Pulmonary Hypertension associated with Idiopathic Interstitial Pneumonias (RISE-IIP), a randomized, controlled, phase 2b trial of riociguat for pulmonary hypertension associated with idiopathic interstitial pneumonia, was terminated early due to increased mortality in riociguat-treated patients. Baseline characteristics of enrolled patients demonstrated a low diffusing capacity of the lung for carbon monoxide (DLCO) with preserved lung volumes at baseline, suggesting the presence of combined pulmonary fibrosis and emphysema (CPFE) in some patients. This post hoc analysis of RISE-IIP was undertaken to explore lung morphology, assessed by high-resolution computed tomography, and associated clinical outcomes.METHODS: Available baseline/pre-baseline high-resolution computed tomography scans were reviewed centrally by 2 radiologists. The extent of emphysema and fibrosis was retrospectively scored and combined to provide the total CPFE score.RESULTS: Data were available for 65/147 patients (44%), including 15/27 fatal cases (56%). Of these, 41/65 patients (63%) had CPFE. Mortality was higher in patients with CPFE (12/41; 29%) than those without (3/24; 13%). Fourteen patients with CPFE had emphysema > fibrosis (4 died). No relationship was observed between CPFE score, survival status, and treatment assignment. A low DLCO, short 6 min walking distance, and high forced vital capacity:DLCO ratio at baseline also appeared to be risk factors for mortality.CONCLUSIONS: High parenchymal lung disease burden and the presence of more emphysema than fibrosis might have predisposed patients with pulmonary hypertension associated with idiopathic interstitial pneumonia to poor outcomes in RISE-IIP. Future studies of therapy for group 3 pulmonary hypertension should include centrally adjudicated imaging for morphologic phenotyping and disease burden evaluation during screening.
AU  - Nathan, S.D.*
AU  - Cottin, V.*
AU  - Behr, J.
AU  - Hoeper, M.M.*
AU  - Martinez, F.J.*
AU  - Corte, T.J.*
AU  - Keogh, A.M.*
AU  - Leuchte, H.*
AU  - Mogulkoc, N.*
AU  - Ulrich, S.*
AU  - Wuyts, W.A.*
AU  - Yao, Z.*
AU  - Ley-Zaporozhan, J.*
AU  - Mueller-Lisse, U.G.*
AU  - Scholle, F.*
AU  - Brueggenwerth, G.*
AU  - Busse, D.*
AU  - Nikkho, S.*
AU  - Wells, A.U.*
C1  - 62234
C2  - 50689
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 494-503
TI  - Impact of lung morphology on clinical outcomes with riociguat in patients with pulmonary hypertension and idiopathic interstitial pneumonia: A post hoc subgroup analysis of the RISE-IIP study.
JO  - J. Heart Lung Transpl.
VL  - 40
IS  - 6
PB  - Elsevier Science Inc
PY  - 2021
SN  - 1053-2498
ER  - 

TY  - JOUR
AB  - The term idiopathic pulmonary arterial hypertension (IPAH) is used to categorize patients with pre-capillary pulmonary hypertension of unknown origin. There is considerable variability in the clinical presentation of these patients. Using data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension, we performed a cluster analysis of 841 patients with IPAH based on age, sex, diffusion capacity of the lung for carbon monoxide (DLCO; <45% vs ≥45% predicted), smoking status, and presence of comorbidities (obesity, hypertension, coronary heart disease, and diabetes mellitus). A hierarchical agglomerative clustering algorithm was performed using Ward's minimum variance method. The clusters were analyzed in terms of baseline characteristics; survival; and response to pulmonary arterial hypertension (PAH) therapy, expressed as changes from baseline to follow-up in functional class, 6-minute walking distance, cardiac biomarkers, and risk. Three clusters were identified: Cluster 1 (n = 106; 12.6%): median age 45 years, 76% females, no comorbidities, mostly never smokers, DLCO ≥45%; Cluster 2 (n = 301; 35.8%): median age 75 years, 98% females, frequent comorbidities, no smoking history, DLCO mostly ≥45%; and Cluster 3 (n = 434; 51.6%): median age 72 years, 72% males, frequent comorbidities, history of smoking, and low DLCO. Patients in Cluster 1 had a better response to PAH treatment than patients in the 2 other clusters. Survival over 5 years was 84.6% in Cluster 1, 59.2% in Cluster 2, and 42.2% in Cluster 3 (unadjusted p < 0.001 for comparison between all groups). The population of patients diagnosed with IPAH is heterogenous. This cluster analysis identified distinct phenotypes, which differed in clinical presentation, response to therapy, and survival.
AU  - Hoeper, M.M.*
AU  - Pausch, C.*
AU  - Grünig, E.*
AU  - Klose, H.*
AU  - Staehler, G.*
AU  - Huscher, D.*
AU  - Pittrow, D.*
AU  - Olsson, K.M.*
AU  - Vizza, C.D.*
AU  - Gall, H.*
AU  - Benjamin, N.*
AU  - Distler, O.*
AU  - Opitz, C.*
AU  - Gibbs, J.S.R.*
AU  - Delcroix, M.*
AU  - Ghofrani, H.A.*
AU  - Rosenkranz, S.*
AU  - Ewert, R.*
AU  - Kaemmerer, H.*
AU  - Lange, T.J.*
AU  - Kabitz, H.J.*
AU  - Skowasch, D.*
AU  - Skride, A.*
AU  - Jureviciene, E.*
AU  - Paleviciute, E.*
AU  - Miliauskas, S.*
AU  - Claussen, M.*
AU  - Behr, J.
AU  - Milger, K.*
AU  - Halank, M.*
AU  - Wilkens, H.*
AU  - Wirtz, H.*
AU  - Pfeuffer-Jovic, E.*
AU  - Harbaum, L.*
AU  - Scholtz, W.*
AU  - Dumitrescu, D.*
AU  - Bruch, L.*
AU  - Coghlan, G.*
AU  - Neurohr, C.*
AU  - Tsangaris, I.*
AU  - Gorenflo, M.*
AU  - Scelsi, L.*
AU  - Vonk-Noordegraaf, A.*
AU  - Ulrich, S.*
AU  - Held, M.*
C1  - 60362
C2  - 49388
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 1435-1444
TI  - Idiopathic pulmonary arterial hypertension phenotypes determined by cluster analysis from the COMPERA registry.
JO  - J. Heart Lung Transpl.
VL  - 39
IS  - 12
PB  - Elsevier Science Inc
PY  - 2020
SN  - 1053-2498
ER  - 

TY  - JOUR
AU  - Liu, H.*
AU  - Zistler, K.*
AU  - Jeridi, A.
AU  - Morrone, C.
AU  - Schulte-Doeinghaus, S.*
AU  - Hagl, C.*
AU  - Yildirim, A.Ö.
AU  - Michel, S.*
AU  - Dashkevich, A.*
C1  - 58907
C2  - 48458
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - S22
TI  - Rapid activation of pro-lymphangiogenic phenotype and consequent increase of lymphatic density occurs during the development of chronic lung allograft dysfunction.
JO  - J. Heart Lung Transpl.
VL  - 39
IS  - 4
PB  - Elsevier Science Inc
PY  - 2020
SN  - 1053-2498
ER  - 

TY  - JOUR
AU  - Morrone, C.
AU  - Rehm, S.R.T.
AU  - Smirnova, N.*
AU  - Doryab, A.
AU  - Schmid, O.
AU  - Eickelberg, O.*
AU  - Yildirim, A.Ö.
AU  - Jenne, D.
C1  - 58908
C2  - 48459
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - S356-S357
TI  - Regulation of cysteine-protease activity prevents graft dysfunction during ischemia-lung reperfusion.
JO  - J. Heart Lung Transpl.
VL  - 39
IS  - 4
PB  - Elsevier Science Inc
PY  - 2020
SN  - 1053-2498
ER  - 

TY  - JOUR
AU  - Morrone, C.
AU  - Smirnova, N.F.*
AU  - Kneidinger, N.*
AU  - Schiller, H. B.
AU  - Eickelberg, O.*
AU  - Yildirim, A.Ö.
C1  - 55807
C2  - 46578
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - S250-S250
TI  - Elevetad cysteine-protease activity in bronchiolitis obliterans syndrome.
JO  - J. Heart Lung Transpl.
VL  - 38
IS  - 4
PB  - Elsevier Science Inc
PY  - 2019
SN  - 1053-2498
ER  - 

TY  - JOUR
AB  - BACKGROUND: Vascular damage and primary graft dysfunction increase with prolonged preservation times of transplanted donor lungs. Hence, storage and conservation of donated lungs in protein-free, dextran-containing electrolyte solutions, like Perfadex, is limited to about 6 hours. We hypothesized that transplanted lungs are protected against neutrophil-mediated proteolytic damage by adding alpha(1)-antitrypsin (AAT), a highly abundant human plasma proteinase inhibitor, to Perfadex.METHODS: A realistic clinically oriented murine model of lung transplantation was used to simulate the ischemia-reperfusion process. Lung grafts were stored at 4 degrees C in Perfadex solution supplemented with AAT or an AAT mutant devoid of elastase-inhibiting activity for 18 hours. We examined wild-type and proteinase 3/neutrophil elastase (PR3/NE) double-deficient mice as graft recipients. Gas exchange function and infiltrating neutrophils of the transplanted lung, as well as protein content and neutrophil numbers in the bronchoalveolar lavage fluid, were determined.RESULTS: AAT as a supplement to Perfadex reduced the extent of primary graft dysfunction and early neutrophil responses after extended storage for 18 hours at 4 degrees C and 4-hour reperfusion in the recipients. Double-knockout recipients that lack elastase-like activities in neutrophils were also protected from early reperfusion injury, but not lung grafts that were perfused with a reactive center mutant of AAT devoid of elastase-inhibiting activity.CONCLUSIONS: PR3 and NE, the principal targets of AAT, are major triggers of post-ischemic reperfusion damage. Their effective inhibition in the graft and recipient is a promising strategy for organ usage after storage for >6 hours. (C) 2018 The Authors. Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation.
AU  - Götzfried, J.
AU  - Smirnova, N.F.
AU  - Morrone, C.
AU  - Korkmaz, B.*
AU  - Yildirim, A.Ö.
AU  - Eickelberg, O.
AU  - Jenne, D.
C1  - 53552
C2  - 44892
CY  - 360 Park Ave South, New York, Ny 10010-1710 Usa
SP  - 1021-1028
TI  - Preservation with alpha(1)-antitrypsin improves primary graft function of murine lung transplants.
JO  - J. Heart Lung Transpl.
VL  - 37
IS  - 8
PB  - Elsevier Science Inc
PY  - 2018
SN  - 1053-2498
ER  - 

TY  - JOUR
AB  - BACKGROUND: Anti-fibrotic drugs may interfere with wound-healing after major surgery, theoretically preventing sufficient bronchial anastomosis formation after lung transplantation (LTx). The aim of this study was to assess the impact of previous treatment with pirfenidone and nintedanib on outcomes after LTx in patients with idiopathic pulmonary fibrosis (IPF). METHODS: All patients with IPF undergoing LTx at the University of Munich between January 2012 and November 2016 were retrospectively screened for previous use of anti-fibrotics. Post-transplant outcome and survival of patients with and without anti-fibrotic treatment were analyzed. RESULTS: A total of 62 patients with IPF were transplanted (lung allocation score [mean +/- SD] +/- 53.1 16.1). Of these, 23 (37.1%) received pirfenidone and 7 (11.3%) received nintedanib before LTx; the remaining 32 (51.6%) did not receive any anti-fibrotic drug (control group). Patients receiving anti-fibrotics were significantly older (p = 0.004) and their carbon monoxide diffusion capacity was significantly higher (p = 0.008) than in controls. Previous anti-fibrotic treatment did not increase blood product utilization, wound-healing or anastomotic complications after LTx. Post-transplant surgical revisions due to bleeding and/or impaired wound-healing were necessary in 18 (29.0%) patients (pirfenidone 30.4%, nintedanib 14.3%, control 31.3%; p = 0.66). Anastomosis insufficiency occurred in 2 (3.2%) patients, both in the control group. No patient died within the first 30 days post-LTx, and no significant differences regarding survival were seen during the follow-up (12-month survival: pirfenidone 77.0%, nintedanib 100%, control 90.6%; p = 0.29). CONCLUSION: Our data show that previous use of anti-fibrotic therapy does not increase surgical complications or post-operative mortality after LTx. (C) 2018 International Society for Heart and Lung Transplantation. All rights reserved.
AU  - Leuschner, G.*
AU  - Stocker, F.*
AU  - Veit, T.*
AU  - Kneidinger, N.*
AU  - Winter, H.*
AU  - Schramm, R.*
AU  - Weig, T.*
AU  - Matthes, S.*
AU  - Ceelen, F.*
AU  - Arnold, P.*
AU  - Munker, D.*
AU  - Klenner, F.*
AU  - Hatz, R.*
AU  - Frankenberger, M.
AU  - Behr, J.*
AU  - Neurohr, C.*
C1  - 51573
C2  - 43309
CY  - New York
SP  - 268-274
TI  - Outcome of lung transplantation in idiopathic pulmonary fibrosis with previous anti-fibrotic therapy.
JO  - J. Heart Lung Transpl.
VL  - 37
IS  - 2
PB  - Elsevier Science Inc
PY  - 2018
SN  - 1053-2498
ER  - 

TY  - JOUR
AU  - Morrone, C.
C1  - 53572
C2  - 44750
SP  - S123-S123
TI  - Inhibition of neutrophil serine proteases by alpha 1 antitrypsin in during storage preserves primary graft functions of transplanted murine donor lungs.
JO  - J. Heart Lung Transpl.
VL  - 37
IS  - 4
PY  - 2018
SN  - 1053-2498
ER  - 

TY  - JOUR
AB  - BACKGROUND: Pulmonary hypertension (PH) is a severe, progressive disease. Although 5 PH subgroups are recognized, reports on survival have focused mainly on pulmonary arterial hypertension (PAH). METHODS: Long-term transplant-free survival and its determinants were investigated in patients with PH (diagnosed by right heart catheterization) within a prospective registry at a single referral center in Giessen, Germany. RESULTS: In total, 2,067 patients were enrolled (PAH, 685 patients [33.1%]; pulmonary venous hypertension, 307 patients [14.9%]; PH due to lung diseases (LD-PH), 546 patients [26.4%; mainly interstitial lung disease and chronic obstructive pulmonary disease]; chronic thromboembolic PH, 459 patients [22.2%]; PH owing to miscellaneous/unknown causes, 70 patients [3.4%]). Median follow-up was 37 months. Differences in transplant-free survival between etiologic groups were highly significant (p < 0.001), with 1-, 3- and 5-year survival rates of 88.2%, 72.2% and 59.4%, respectively, for those with PAH compared with 79.5%, 52.7% and 38.1%, respectively, for patients with LD-PH. Patients' age, gender and 6-minute walk distance (6MWD), but not New York Heart Association (NYHA) functional class, associated significantly with survival across all PH subtypes in multivariate Cox regression analyses. CONCLUSIONS: This is the largest single-center PH cohort described so far. Some parameters used in clinical practice do not independently predict survival. Age, gender and 6MWD outperformed NYHA functional class in predicting survival across all etiologic groups.
AU  - Gall, H.*
AU  - Felix, J.F.*
AU  - Schneck, F.K.*
AU  - Milger, K.
AU  - Sommer, N.*
AU  - Voswinckel, R.*
AU  - Franco, O.H.*
AU  - Hofman, A.*
AU  - Schermuly, R.T.*
AU  - Weissmann, N.*
AU  - Grimminger, F.*
AU  - Seeger, W.*
AU  - Ghofrani, H.A.*
C1  - 50730
C2  - 42868
CY  - New York
SP  - 957-967
TI  - The Giessen Pulmonary Hypertension Registry: Survival in pulmonary hypertension subgroups.
JO  - J. Heart Lung Transpl.
VL  - 36
IS  - 9
PB  - Elsevier Science Inc
PY  - 2017
SN  - 1053-2498
ER  - 

TY  - JOUR
AB  - BACKGROUND: Hospital treatment costs of lung transplantation are insufficiently analyzed. Accordingly, it remains unknown, whether current Diagnosis Related Groups, merely accounting for 3 ventilation time intervals and length of hospital stay, reproduce costs properly, even when an increasing number of complex recipients are treated. Therefore, in this cost determination study, actual costs were calculated and cost drivers identified. METHODS: A standardized microcosting approach allowed for individual cost calculations in 780 lung transplant patients taken care of at Hannover Medical School and University of Munich from 2009 to 2013. A generalized linear model facilitated the determination of characteristics predictive for inpatient costs. RESULTS: Lung transplantation costs varied substantially by major diagnosis, with a mean of €85,946 (median €52,938 ± 3,081). Length of stay and ventilation time properly reproduced costs in many cases. However, complications requiring prolonged ventilation or reinterventions were identified as additional significant cost drivers, responsible for high costs. CONCLUSIONS: Diagnosis Related Groups properly reproduce actual lung transplantation costs in straightforward cases, but costs in complex cases may remain underestimated. Improved grouping should consider major diagnosis, a higher gradation of ventilation time, and the number of reinterventions to allow for more reasonable reimbursement.
AU  - Vogl, M.
AU  - Warnecke, G.*
AU  - Haverich, A.*
AU  - Gottlieb, J.*
AU  - Welte, T.*
AU  - Hatz, R.A.*
AU  - Hunger, M.
AU  - Leidl, R.
AU  - Lingner, H.*
AU  - Behr, J.*
AU  - Winter, H.*
AU  - Schramm, R.*
AU  - Zwissler, B.*
AU  - Hagl, C.*
AU  - Strobl, N.*
AU  - Jaeger, C.*
AU  - Preissler, G.*
C1  - 49010
C2  - 41546
CY  - New York
SP  - 1227-1236
TI  - Lung transplantation in the spotlight: Reasons for high-cost procedures.
JO  - J. Heart Lung Transpl.
VL  - 35
IS  - 10
PB  - Elsevier Science Inc
PY  - 2016
SN  - 1053-2498
ER  - 

TY  - JOUR
AU  - Überfuhr, P.*
AU  - Meiser, B.*
AU  - Fuchs, A.*
AU  - Schulze, C.*
AU  - Reichenspurner, H.*
AU  - Falk, M.
AU  - Weiss, M.*
AU  - Wintersperger, B.*
AU  - Issels, R.D.
AU  - Reichart, B.*
C1  - 22149
C2  - 20842
SP  - 1135-1139
TI  - Heart Transplantation : An Approach to Treating Primary Cardiac Sarcoma ?.
JO  - J. Heart Lung Transpl.
VL  - 21
PY  - 2002
SN  - 1053-2498
ER  -