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1. OPTImal PHARMacological therapy for patients with heart failure: Rationale and design of the OPTIPHARM-HF registry

Author

Inciardi, R, Vaduganathan, M, Lombardi, C, Gussago, C, Agostoni, P, Ameri, P, Aspromonte, N, Calo, L, Cameli, M, Carluccio, E, Carugo, S, Cipriani, M, De Caterina, R, De Ferrari, G, Emdin, M, Fornaro, A, Guazzi, M, Iacoviello, M, Imazio, M, La Rovere, M, Leonardi, S, Maccallini, M, Masarone, D, Moschini, L, Palazzuoli, A, Patti, G, Pedretti, R, Perrone Filardi, P, Piepoli, M, Potena, L, Salzano, A, Sciacqua, A, Senni, M, Sinagra, G, Specchia, C, Taddei, S, Vizza, D, Savarese, G, Rosano, G, Volterrani, M, Metra, M, Adamo, M, Armentaro, G, Attanasio, A, Badagliacca, R, Brunetti, N, Bursi, F, Canonero, M, Caporotondi, A, Cassano, V, Cice, G, Cimino, G, Clemenza, F, Correale, M, D'Elia, E, Fiorentino, L, Foa, A, Fornaro, P, Ghio, S, Guerisoli, L, Iseppi, M, Manai, R, Mandoli, G, Marini, S, Marsico, F, Masini, G, Mauro, C, Mazzoni, A, Mazzotta, M, Merlo, M, Nodari, S, Novarese, F, Oriecuia, C, Pagnesi, M, Paolillo, S, Pastore, M, Pugliese, N, Raineri, C, Ramani, F, Sabatino, M, Scelsi, L, Spoto, G, Stolfo, D, Tarantini, R, Vizzardi, E, Zampieri, M, Inciardi R. M., Vaduganathan M., Lombardi C. M., Gussago C., Agostoni P., Ameri P., Aspromonte N., Calo L., Cameli M., Carluccio E., Carugo S., Cipriani M., De Caterina R., De Ferrari G. M., Emdin M., Fornaro A., Guazzi M., Iacoviello M., Imazio M., La Rovere M. T., Leonardi S., Maccallini M., Masarone D., Moschini L., Palazzuoli A., Patti G., Pedretti R. F. E., Perrone Filardi P., Piepoli M. F., Potena L., Salzano A., Sciacqua A., Senni M., Sinagra G., Specchia C., Taddei S., Vizza D., Savarese G., Rosano G., Volterrani M., Metra M., Adamo M., Armentaro G., Attanasio A., Badagliacca R., Brunetti N., Bursi F., Canonero M., Caporotondi A., Cassano V., Cice G., Cimino G., Clemenza F., Correale M., D'Elia E., Fiorentino L., Foa A., Fornaro P., Ghio S., Guerisoli L., Iseppi M., Manai R., Mandoli G. E., Marini S. C., Marsico F., Masini G., Mauro C., Mazzoni A., Mazzotta M., Merlo M., Nodari S., Novarese F., Oriecuia C., Pagnesi M., Paolillo S., Pastore M. C., Pugliese N. R., Raineri C., Ramani F., Sabatino M., Scelsi L., Spoto G., Stolfo D., Tarantini R., Vizzardi E., Zampieri M., Inciardi, R, Vaduganathan, M, Lombardi, C, Gussago, C, Agostoni, P, Ameri, P, Aspromonte, N, Calo, L, Cameli, M, Carluccio, E, Carugo, S, Cipriani, M, De Caterina, R, De Ferrari, G, Emdin, M, Fornaro, A, Guazzi, M, Iacoviello, M, Imazio, M, La Rovere, M, Leonardi, S, Maccallini, M, Masarone, D, Moschini, L, Palazzuoli, A, Patti, G, Pedretti, R, Perrone Filardi, P, Piepoli, M, Potena, L, Salzano, A, Sciacqua, A, Senni, M, Sinagra, G, Specchia, C, Taddei, S, Vizza, D, Savarese, G, Rosano, G, Volterrani, M, Metra, M, Adamo, M, Armentaro, G, Attanasio, A, Badagliacca, R, Brunetti, N, Bursi, F, Canonero, M, Caporotondi, A, Cassano, V, Cice, G, Cimino, G, Clemenza, F, Correale, M, D'Elia, E, Fiorentino, L, Foa, A, Fornaro, P, Ghio, S, Guerisoli, L, Iseppi, M, Manai, R, Mandoli, G, Marini, S, Marsico, F, Masini, G, Mauro, C, Mazzoni, A, Mazzotta, M, Merlo, M, Nodari, S, Novarese, F, Oriecuia, C, Pagnesi, M, Paolillo, S, Pastore, M, Pugliese, N, Raineri, C, Ramani, F, Sabatino, M, Scelsi, L, Spoto, G, Stolfo, D, Tarantini, R, Vizzardi, E, Zampieri, M, Inciardi R. M., Vaduganathan M., Lombardi C. M., Gussago C., Agostoni P., Ameri P., Aspromonte N., Calo L., Cameli M., Carluccio E., Carugo S., Cipriani M., De Caterina R., De Ferrari G. M., Emdin M., Fornaro A., Guazzi M., Iacoviello M., Imazio M., La Rovere M. T., Leonardi S., Maccallini M., Masarone D., Moschini L., Palazzuoli A., Patti G., Pedretti R. F. E., Perrone Filardi P., Piepoli M. F., Potena L., Salzano A., Sciacqua A., Senni M., Sinagra G., Specchia C., Taddei S., Vizza D., Savarese G., Rosano G., Volterrani M., Metra M., Adamo M., Armentaro G., Attanasio A., Badagliacca R., Brunetti N., Bursi F., Canonero M., Caporotondi A., Cassano V., Cice G., Cimino G., Clemenza F., Correale M., D'Elia E., Fiorentino L., Foa A., Fornaro P., Ghio S., Guerisoli L., Iseppi M., Manai R., Mandoli G. E., Marini S. C., Marsico F., Masini G., Mauro C., Mazzoni A., Mazzotta M., Merlo M., Nodari S., Novarese F., Oriecuia C., Pagnesi M., Paolillo S., Pastore M. C., Pugliese N. R., Raineri C., Ramani F., Sabatino M., Scelsi L., Spoto G., Stolfo D., Tarantini R., Vizzardi E., and Zampieri M.

Abstract

Aims: Patients with heart failure (HF) remain often undertreated for multiple reasons, including treatment inertia, contraindications, and intolerance. The OPTIimal PHARMacological therapy for patients with Heart Failure (OPTIPHARM-HF) registry is designed to evaluate the prevalence of evidence-based medical treatment prescription and titration, as well as the causes of its underuse, in a broad real-world population of consecutive patients with HF across the whole ejection fraction spectrum and among different clinical phenotypes. Methods: The OPTIPHARM-HF registry (NCT06192524) is a prospective, multicenter, observational, national study of adult patients with symptomatic HF, as defined by current international guidelines, regardless of ejection fraction. Both outpatients and inpatients with chronic and acute decompensated HF will be recruited. The study will enroll up to 2500 patients with chronic HF at approximately 35 Italian HF centres. Patients will be followed for a maximum duration of 24 months. The primary objective of the OPTIPHARM-HF registry is to assess prescription and adherence to evidence-based guideline-directed medical therapy (GDMT) in patients with HF. The primary outcome is to describe the prevalence of GDMT use according to target guideline recommendation. Secondary objectives include implementation of comorbidity treatment, evaluation of sequence of treatment introduction and up-titration, description of GDMT implementation in the specific HF population, main causes of GDMT underuse, and assessment of cumulative rate of cardiovascular events. Conclusion: The OPTIPHARM-HF registry will provide important implications for improving patient care and adoption of recommended medical therapy into clinical practice among HF patients.

Published
2024

3. Switching to riociguat versus maintenance therapy with phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension (REPLACE): a multicentre, open-label, randomised controlled trial

Author

Olschewski, H, Delcroix, M, Andrade-Lima, M, de Amorim Corrêac, R, Figueiredo Campos, F, Ota Arakaki, J, Meyer, G, De Souza, R, Langleben, D, Al-Hiti, H, Jansa, P, Mellemkjær, S, Bauer, F, Montani, D, Simonneau, G, Drömann, D, Ghofrani, H-A, Grünig, E, Halank, M, Held, M, Hoeper, MM, Klose, H, Kneidinger, N, Leuchte, H, Opitz, C, Rosenkranz, S, Wilkens, H, Wirtz, H, Karvounis, H, Pitsiou, G, Orfanos, S, D'Alto, M, Ghio, S, Vizza, CD, Vitulo, P, Nakayama, T, Maki, H, Tatebe, S, de los Rios Ibarra, M, Pulido, T, Van Dijk, A, Vonk-Noordegraaf, A, Roleder, T, Castro, G, Loureiro, MJ, Robalo-Martins, S, Barberá, JA, Lázaro, M, Perez-Penate, GM, Román, A, Cheng, C-C, Hsu, C-H, Hsu, H-H, Atahan, E, Mogulkoc Bishop, N, Okumus, NG, Onen, Z, Chang, H-J, Chang, S-A, Lee, J-S, Kim, H-K, Coghlan, JG, Corris, PA, Church, AC, Condliffe, R, Gibbs, JSR, Peacock, AJ, Wort, S, Allen, R, Allen, S, Awdish, R, Benza, RL, DeSouza, S, Feldman, J, Johri, S, Klinger, JR, Layish, D, McConnell, J, McLaughlin, VV, Migliore, C, Rahaghi, F, Rischard, F, Robbins, I, Satterwhite, L, Shah, T, Sulica, R, White, RJ, Hoeper, Marius M, Al-Hiti, Hikmet, Benza, Raymond L, Chang, Sung-A, Corris, Paul A, Gibbs, J Simon R, Grünig, Ekkehard, Jansa, Pavel, Klinger, James R, Langleben, David, McLaughlin, Vallerie V, Meyer, Gisela M B, Ota-Arakaki, Jaquelina, Peacock, Andrew J, Pulido, Tomás, Rosenkranz, Stephan, Vizza, Carmine Dario, Vonk-Noordegraaf, Anton, White, R James, Chang, Mikyung, Kleinjung, Frank, Meier, Christian, Paraschin, Karen, Ghofrani, Hossein Ardeschir, and Simonneau, Gérald

Published
2021
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4. Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial

Author

Azize, G, Fernandez, A, Zapata, GO, Garcia Pacho, P, Glenny, A, Ferre Pacora, F, Parody, ML, Bono, J, Beltrano, C, Hershson, A, Vita, N, Luquez, HA, Cestari, HG, Fernandez, H, Prado, A, Berli, M, García Durán, R, Thierer, J, Diez, M, Lobo Marquez, L, Borelli, RR, Hominal, MÁ, Metra, M, Ameri, P, Agostoni, P, Salvioni, A, Fattore, L, Gronda, E, Ghio, S, Turrini, F, Uguccioni, M, Di Biase, M, Piepoli, M, Savonitto, S, Mortara, A, Terrosu, P, Fucili, A, Boriani, G, Midi, P, Passamonti, E, Cosmi, F, van der Meer, P, Van Bergen, P, van de Wetering, M, Al-Windy, NYY, Tanis, W, Meijs, M, Groutars, RGEJ, The, HKS, Kietselaer, B, van Kesteren, HAM, Beelen, DPW, Heymeriks, J, Van de Wal, R, Schaap, J, Emans, M, Westendorp, P, Nierop, PR, Nijmeijer, R, Manintveld, OC, Dorobantu, M, Darabantiu, DA, Zdrenghea, D, Toader, DM, Petrescu, L, Militaru, C, Crisu, D, Tomescu, MC, Stanciulescu, G, Rodica Dan, A, Iosipescu, LC, Serban, DL, Drozdz, J, Szachniewicz, J, Bronisz, M, Tycińska, A, Wozakowska-Kaplon, B, Mirek-Bryniarska, E, Gruchała, M, Nessler, J, Straburzyńska-Migaj, E, Mizia-Stec, K, Szelemej, R, Gil, R, Gąsior, M, Gotsman, I, Halabi, M, Shochat, M, Shechter, M, Witzling, V, Zukermann, R, Arbel, Y, Flugelman, M, Ben-Gal, T, Zvi, V, Kinany, W, Weinstein, JM, Atar, S, Goland, S, Milicic, D, Horvat, D, Tušek, S, Udovicic, M, Šutalo, K, Samodol, A, Pesek, K, Artuković, M, Ružić, A, Šikić, J, McDonagh, T, Trevelyan, J, Wong, Y-K, Gorog, D, Ray, R, Pettit, S, Sharma, S, Kabir, A, Hamdan, H, Tilling, L, Baracioli, L, Nigro Maia, L, Dutra, O, Reis, G, Pimentel Filho, P, Saraiva, JF, Kormann, A, dos Santos, FR, Bodanese, L, Almeida, D, Precoma, D, Rassi, S, Costa, F, Kabbani, S, Abdelbaki, K, Abdallah, C, Arnaout, MS, Azar, R, Chaaban, S, Raed, O, Kiwan, G, Hassouna, B, Bardaji, A, Zamorano, J, del Prado, S, Gonzalez Juanatey, JR, Ga Bosa Ojeda, FI, Gomez Bueno, M, Molina, BD, Pascual Figal, DA, Sim, D, Yeo, TJ, Loh, SY, Soon, D, Ohlsson, M, Smith, JG, Gerward, S, Khintibidze, I, Lominadze, Z, Chapidze, G, Emukhvari, N, Khabeishvili, G, Chumburidze, V, Paposhvili, K, Shaburishvili, T, Parhomenko, O, Kraiz, I, Koval, O, Zolotaikina, V, Malynovsky, Y, Vakaliuk, I, Rudenko, L, Tseluyko, V, Stanislavchuk, M, Ponikowski, Piotr, Kirwan, Bridget-Anne, Anker, Stefan D, McDonagh, Theresa, Dorobantu, Maria, Drozdz, Jarosław, Fabien, Vincent, Filippatos, Gerasimos, Göhring, Udo Michael, Keren, Andre, Khintibidze, Irakli, Kragten, Hans, Martinez, Felipe A, Metra, Marco, Milicic, Davor, Nicolau, José C, Ohlsson, Marcus, Parkhomenko, Alexander, Pascual-Figal, Domingo A, Ruschitzka, Frank, Sim, David, Skouri, Hadi, van der Meer, Peter, Lewis, Basil S, Comin-Colet, Josep, von Haehling, Stephan, Cohen-Solal, Alain, Danchin, Nicolas, Doehner, Wolfram, Dargie, Henry J, Motro, Michael, Butler, Javed, Friede, Tim, Jensen, Klaus H, Pocock, Stuart, and Jankowska, Ewa A

Published
2020
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5. Management and outcome of high-risk pulmonary embolism in intensive care units: results from a retrospective single-center analysis

Author

Colombo, C N J, primary, Guglielmi, A, additional, Caneva, L, additional, Patrini, L, additional, Rossi, F, additional, Ambrosini, E, additional, Turco, A, additional, Capra Marzani, F, additional, Scelsi, L, additional, Pagani, M, additional, Camporotondo, R, additional, Ghio, S, additional, and Tavazzi, G, additional

Published
2024
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6. Bridging the gap in the symptomatic heart failure patient journey: insights from the Italian scenario

Author

Ziacchi, M, Spadotto, A, Ghio, S, Pellegrino, M, Potena, L, Masarone, D, Merlo, M, Stolfo, D, Caracciolo, M, Inserra, C, Ammirati, F, Ciccarelli, M, Colivicchi, F, Bianchi, S, Patti, G, Oliva, F, Arcidiacono, G, Rordorf, R, Pini, D, Pacileo, G, D'Onofrio, A, Forleo, G, Mariani, M, Adamo, F, Alonzo, A, Ruzzolini, M, Ghiglieno, C, Cipriani, M, Firetto, G, Aspromonte, N, Clemenza, F, Maria De Ferrari, G, Senni, M, Grazia Bongiorni, M, Tondo, C, Grimaldi, M, Giallauria, F, Rametta, F, Marchese, P, Biffi, M, Sinagra, G, Ziacchi M., Spadotto A., Ghio S., Pellegrino M., Potena L., Masarone D., Merlo M., Stolfo D., Caracciolo M. M., Inserra C., Ammirati F., Ciccarelli M., Colivicchi F., Bianchi S., Patti G., Oliva F., Arcidiacono G., Rordorf R., Pini D., Pacileo G., D'Onofrio A., Forleo G. B., Mariani M., Adamo F., Alonzo A., Ruzzolini M., Ghiglieno C., Cipriani M., Firetto G., Aspromonte N., Clemenza F., Maria De Ferrari G., Senni M., Grazia Bongiorni M., Tondo C., Grimaldi M., Giallauria F., Rametta F., Marchese P., Biffi M., Sinagra G., Ziacchi, M, Spadotto, A, Ghio, S, Pellegrino, M, Potena, L, Masarone, D, Merlo, M, Stolfo, D, Caracciolo, M, Inserra, C, Ammirati, F, Ciccarelli, M, Colivicchi, F, Bianchi, S, Patti, G, Oliva, F, Arcidiacono, G, Rordorf, R, Pini, D, Pacileo, G, D'Onofrio, A, Forleo, G, Mariani, M, Adamo, F, Alonzo, A, Ruzzolini, M, Ghiglieno, C, Cipriani, M, Firetto, G, Aspromonte, N, Clemenza, F, Maria De Ferrari, G, Senni, M, Grazia Bongiorni, M, Tondo, C, Grimaldi, M, Giallauria, F, Rametta, F, Marchese, P, Biffi, M, Sinagra, G, Ziacchi M., Spadotto A., Ghio S., Pellegrino M., Potena L., Masarone D., Merlo M., Stolfo D., Caracciolo M. M., Inserra C., Ammirati F., Ciccarelli M., Colivicchi F., Bianchi S., Patti G., Oliva F., Arcidiacono G., Rordorf R., Pini D., Pacileo G., D'Onofrio A., Forleo G. B., Mariani M., Adamo F., Alonzo A., Ruzzolini M., Ghiglieno C., Cipriani M., Firetto G., Aspromonte N., Clemenza F., Maria De Ferrari G., Senni M., Grazia Bongiorni M., Tondo C., Grimaldi M., Giallauria F., Rametta F., Marchese P., Biffi M., and Sinagra G.

Abstract

Background: The prognosis for heart failure (HF) patients remains poor, with a high mortality rate, and a marked reduction in quality of life (QOL) and functional status. This study aims to explore the ongoing needs of HF management and the epidemiology of patients followed by Italian HF clinics, with a specific focus on cardiac contractility modulation (CCM). Research design and methods: Data from patients admitted to 14 HF outpatients clinics over 4 weeks were collected and compared to the results of a survey open to physicians involved in HF management operating in Italian centers. Results: One hundred and five physicians took part in the survey. Despite 94% of patients receive a regular follow-up every 3–6 months, available therapies are considered insufficient in 30% of cases. Physicians reported a lack of treatment options for 23% of symptomatic patients with reduced ejection fraction (EF) and for 66% of those without reduced EF. Approximately 3% of HF population (two patients per month per HF clinic) meets the criteria for immediate CCM treatment, which is considered a useful option by 15% of survey respondents. Conclusions: Despite this relatively small percentage, considering total HF population, CCM could potentially benefit numerous HF patients, particularly the elderly, by reducing hospitalizations, improving functional capacity and QOL.

Published
2023

7. Sodium nitroprusside for advanced heart failure. A metanalysis of literature data

Author

Ghio, S, Mandurino-Mirizzi, A, La Rovere, M, Traversi, E, Lombardi, C, Scelsi, L, Senni, M, Iacovoni, A, Ghio S., Mandurino-Mirizzi A., La Rovere M. T., Traversi E., Lombardi C., Scelsi L., Senni M., Iacovoni A., Ghio, S, Mandurino-Mirizzi, A, La Rovere, M, Traversi, E, Lombardi, C, Scelsi, L, Senni, M, Iacovoni, A, Ghio S., Mandurino-Mirizzi A., La Rovere M. T., Traversi E., Lombardi C., Scelsi L., Senni M., and Iacovoni A.

Abstract

Advanced heart failure (HF) is associated with a very poor prognosis and places a big burden on health-care services. The gold standard treatment, i.e. long-term mechanical circulatory support or heart transplantation, is precluded in many patients but observational studies suggest that the use of SNP might be associated with favourable long-term clinical outcomes. We performed a metanalysis of published studies that compared sodium nitroprusside (SNP) with optimal medical therapy to examine the safety and efficacy of SNP as part of the treatment regimen of patients hospitalized for advanced heart failure (HF). We searched PUBMED, EMBASE and WEB OF SCIENCE for studies that compared SNP with optimal medical therapy in advanced HF on July 2022. After screening 700 full-text articles, data from two original articles were included in a combined analysis. The analysis demonstrated a 66% reduction in the odds of death in advanced HF patients treated with SNP. The results show the potential importance of the inclusion of SNP in the treatment regimen of patients hospitalized because of advanced HF and underlines that controlled, randomized studies are still required in this condition.

Published
2023

9. Imaging the right atrium in pulmonary hypertension: A systematic review and meta-analysis.

Author

Richter, M.J., Fortuni, F., Alenezi, F., D'Alto, M., Badagliacca, R., Brunner, N.W., Dijk, A.P. van, Douschan, P., Gall, H., Ghio, S., Giudice, F.L., Grünig, E., Haddad, F., Howard, L., Rajagopal, Sudarshan, Stens, N.A., Stolfo, D., Thijssen, D.H.J., Vizza, C.D., Zamanian, R.T., Zhong, L., Seeger, W., Ghofrani, H.A., Tello, K., Richter, M.J., Fortuni, F., Alenezi, F., D'Alto, M., Badagliacca, R., Brunner, N.W., Dijk, A.P. van, Douschan, P., Gall, H., Ghio, S., Giudice, F.L., Grünig, E., Haddad, F., Howard, L., Rajagopal, Sudarshan, Stens, N.A., Stolfo, D., Thijssen, D.H.J., Vizza, C.D., Zamanian, R.T., Zhong, L., Seeger, W., Ghofrani, H.A., and Tello, K.

Abstract

01 april 2023, Item does not contain fulltext, BACKGROUND: Right atrial (RA) imaging has emerged as a promising tool for the evaluation of patients with pulmonary hypertension (PH), albeit without systematic validation. METHODS: PubMed, Web of Science and the Cochrane library were searched for studies investigating the prognostic value of RA imaging assessment in patients with PH from 2000 to June 2021 (PROSPERO Identifier: CRD42020212850). An inverse variance-weighted meta-analysis of univariable hazard ratios (HRs) was performed using a random effects model. RESULTS: Thirty-five studies were included (3,476 patients with PH; 74% female, 86% pulmonary arterial hypertension). Risk of bias was low/moderate (Quality of Prognosis Studies checklist). RA area (HR 1.06; 95% confidence interval [CI] 1.04-1.08), RA indexed area (HR 1.09; 95% CI 1.04-1.14), RA peak longitudinal strain (PLS; HR 0.94; 95% CI 0.91-0.97) and RA total emptying fraction (HR 0.96; 95% CI 0.94-0.98) were significantly associated with combined end-points including death, clinical worsening and/or lung transplantation; RA volume and volume index showed marginal significant associations. RA area (HR 1.06; 95% CI 1.04-1.07), RA indexed area (HR 1.12; 95% CI 1.07-1.17) and RA PLS (HR 0.98; 95% CI 0.97-0.99) showed significant associations with mortality; RA total emptying fraction showed a marginal association. CONCLUSIONS: Imaging-based RA assessment qualifies as a relevant prognostic marker in PH. RA area reliably predicts composite end-points and mortality, which underscores its clinical utility. RA PLS emerged as a promising imaging measure, but is currently limited by the number of studies and different acquisition methods.

Published
2023

10. How to fill the gap in the symptomatic HF patient journey between optimal medical therapy and advanced heart failure treatment: two Italian surveys

Author

Spadotto, A, primary, Ziacchi, M, additional, Ghio, S, additional, Pellegrino, M, additional, Masarone, D, additional, Caracciolo, M, additional, Inserra, C A, additional, Ammirati, F, additional, Ciccarelli, M, additional, Colivicchi, F, additional, Bianchi, S, additional, Oliva, F, additional, Biffi, M, additional, and Sinagra, G, additional

Published
2023
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11. C3 OUTCOME OF CARDIAC SYMPATHETIC DENERVATION IN CARDIOMYOPATHIES AND PREDICTORS OF RECURRENCES

Author

Dusi, V, primary, Ruffinazzi, M, additional, Pugliese, L, additional, Guerrera, F, additional, Baldi, E, additional, Sanzo, A, additional, Vicentini, A, additional, Savastano, S, additional, Greco, A, additional, Camporotondo, R, additional, Vairo, A, additional, Frea, S, additional, Proclemer, A, additional, Driussi, M, additional, Massimo, I, additional, Tritto, M, additional, Trompeo, A, additional, Belliato, M, additional, Ghio, S, additional, Raineri, C, additional, Rordorf, R, additional, and De Ferrari, G, additional

Published
2023
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15. Current gaps in HFpEF trials: Time to reconsider patients' selection and to target phenotypes

Author

Palazzuoli, A, Caravita, S, Paolillo, S, Ghio, S, Tocchetti, C, Ruocco, G, Correale, M, Ambrosio, G, Perrone Filardi, P, Senni, M, Italian Society of Cardiology Heart Failure Study, G, Palazzuoli A, Caravita S, Paolillo S, Ghio S, Tocchetti CG, Ruocco G, Correale M, Ambrosio G, Perrone Filardi P, Senni M, Italian Society of Cardiology Heart Failure Study Group, Palazzuoli, A, Caravita, S, Paolillo, S, Ghio, S, Tocchetti, C, Ruocco, G, Correale, M, Ambrosio, G, Perrone Filardi, P, Senni, M, Italian Society of Cardiology Heart Failure Study, G, Palazzuoli A, Caravita S, Paolillo S, Ghio S, Tocchetti CG, Ruocco G, Correale M, Ambrosio G, Perrone Filardi P, Senni M, and Italian Society of Cardiology Heart Failure Study Group

Abstract

Heart Failure with preserved Ejection Fraction (HFpEF) is an increasingly prevalent clinical condition associated with cardiovascular aging, characterized by different pathophysiological mechanisms and poor outcomes. In this manuscript, we analysed the main differences in terms of updated diagnostic criteria and patients' selection in the most recent HFpEF trials. Recent algorithm purposed for HFpEF diagnosis, does not reflect common criteria adopted in clinical trials. Patients included in the larger studies experienced different characteristics in terms of clinical presentation and echocardiographic features. Current concerns complicate results interpretation and could hypothesize different stages of disease progression, rather than different cardiac phenotypes. Both the lack of diagnostic standardization and the population heterogeneity, might explain why trials investigating the effects of different therapeutic interventions failed to show improved outcomes for patients with HFpEF. Accordingly, we propose to exceed current view mainly based on the morphological adaptations evaluating patients' characterisation, their cardiovascular risk, associated diseases, and structural features consistent with disease progression. Detailed clinical, imaging and biological characterisation of this population, along with the identification of mechanisms linked with disease progression and prognosis, would allow for tailored treatments and provide important mechanistic insights into the complex HFpEF pathophysiology.

Published
2021

18. 3D Radar Imaging for Non-Cooperative Target Recognition

Author

Martorella, M., primary, Giusti, E., additional, Ghio, S., additional, Samczynski, P., additional, Drozdowicz, J., additional, Baczyk, M.K., additional, Wielgo, M., additional, Stasiak, K., additional, Julczyk, J., additional, Ciesielski, M., additional, Soszka, M., additional, Mularzuk, R., additional, Pizziol, G., additional, Stagliano, D., additional, and Lischi, S., additional

Published
2022
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19. Mining the Plasma Proteome for Insights into the Molecular Pathology of Pulmonary Arterial Hypertension

Author

Harbaum, Lars, primary, Rhodes, Christopher J., additional, Wharton, John, additional, Lawrie, Allan, additional, Karnes, Jason H., additional, Desai, Ankit A., additional, Nichols, William C., additional, Humbert, Marc, additional, Montani, David, additional, Girerd, Barbara, additional, Sitbon, Olivier, additional, Boehm, Mario, additional, Novoyatleva, Tatyana, additional, Schermuly, Ralph T., additional, Ghofrani, H. Ardeschir, additional, Toshner, Mark, additional, Kiely, David G., additional, Howard, Luke S., additional, Swietlik, Emilia M., additional, Gräf, Stefan, additional, Pietzner, Maik, additional, Morrell, Nicholas W., additional, Wilkins, Martin R., additional, Southgate, L, additional, Machado, RD, additional, Martin, J, additional, Ouwehand, WH, additional, Pauciulo, MW, additional, Arora, A, additional, Lutz, K, additional, Ahmad, F, additional, Archer, SL, additional, Argula, R, additional, Austin, ED, additional, Badesch, D, additional, Bakshi, S, additional, Barnett, C, additional, Benza, R, additional, Bhatt, N, additional, Burger, CD, additional, Chakinala, M, additional, Elwing, J, additional, Fortin, T, additional, Frantz, RP, additional, Frost, A, additional, Garcia, JGN, additional, Harley, J, additional, He, H, additional, Hill, NS, additional, Hirsch, R, additional, Ivy, D, additional, Klinger, J, additional, Lahm, T, additional, Marsolo, K, additional, Martin, LJ, additional, Nathan, SD, additional, Oudiz, RJ, additional, Rehman, Z, additional, Robbins, I, additional, Roden, DM, additional, Rosenzweig, EB, additional, Saydain, G, additional, Schilz, R, additional, Simms, RW, additional, Simon, M, additional, Tang, H, additional, Tchourbanov, AY, additional, Thenappan, T, additional, Torres, F, additional, Walsworth, AK, additional, Walter, RE, additional, White, RJ, additional, Wilt, J, additional, Yung, D, additional, Kittles, R, additional, Aman, J, additional, Knight, J, additional, Hanscombe, KB, additional, Gall, H, additional, Ulrich, A, additional, Bogaard, HJ, additional, Church, C, additional, Coghlan, JG, additional, Condliffe, R, additional, Corris, PA, additional, Danesino, C, additional, Elliott, CG, additional, Franke, A, additional, Ghio, S, additional, Gibbs, JSR, additional, Houweling, AC, additional, Kovacs, G, additional, Laudes, M, additional, MacKenzie Ross, RV, additional, Moledina, S, additional, Newnham, M, additional, Olschewski, A, additional, Olschewski, H, additional, Peacock, AJ, additional, Pepke-Zaba, J, additional, Scelsi, L, additional, Seeger, W, additional, Shaffer, CM, additional, Sitbon, O, additional, Suntharalingam, J, additional, Treacy, C, additional, Vonk Noordegraaf, A, additional, Waisfisz, Q, additional, Wort, SJ, additional, Trembath, RC, additional, Germain, M, additional, Cebola, I, additional, Ferrer, J, additional, Amouyel, P, additional, Debette, S, additional, Eyries, M, additional, Soubrier, F, additional, and Trégouët, DA, additional

Published
2022
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20. Pulmonary Vascular Research Institute GoDeep: A meta-registry merging deep phenotyping datafrom international PH reference centers

Author

Majeed, R.W. Wilkins, M.R. Howard, L. Hassoun, P.M. Anthi, A. Cajigas, H.R. Cannon, J. Chan, S.Y. Damonte, V. Elwing, J. Förster, K. Frantz, R. Ghio, S. Al Ghouleh, I. Hilgendorff, A. Jose, A. Juaneda, E. Kiely, D.G. Lawrie, A. Orfanos, S.E. Pepe, A. Pepke-Zaba, J. Sirenko, Y. Swett, A.J. Torbas, O. Zamanian, R.T. Marquardt, K. Michel-Backofen, A. Antoine, T. Wilhelm, J. Barwick, S. Krieb, P. Fuenderich, M. Fischer, P. Gall, H. Ghofrani, H.-A. Grimminger, F. Tello, K. Richter, M.J. Seeger, W. and Majeed, R.W. Wilkins, M.R. Howard, L. Hassoun, P.M. Anthi, A. Cajigas, H.R. Cannon, J. Chan, S.Y. Damonte, V. Elwing, J. Förster, K. Frantz, R. Ghio, S. Al Ghouleh, I. Hilgendorff, A. Jose, A. Juaneda, E. Kiely, D.G. Lawrie, A. Orfanos, S.E. Pepe, A. Pepke-Zaba, J. Sirenko, Y. Swett, A.J. Torbas, O. Zamanian, R.T. Marquardt, K. Michel-Backofen, A. Antoine, T. Wilhelm, J. Barwick, S. Krieb, P. Fuenderich, M. Fischer, P. Gall, H. Ghofrani, H.-A. Grimminger, F. Tello, K. Richter, M.J. Seeger, W.

Abstract

The Pulmonary Vascular Research Institute GoDeep meta-registry is a collaboration of pulmonary hypertension (PH) reference centers across the globe. Merging worldwide PH data in a central meta-registry to allow advanced analysis of the heterogeneity of PH and its groups/subgroups on a worldwide geographical, ethnical, and etiological landscape (ClinTrial. gov NCT05329714). Retrospective and prospective PH patient data (diagnosis based on catheterization; individuals with exclusion of PH are included as a comparator group) are mapped to a common clinical parameter set of more than 350 items, anonymized and electronically exported to a central server. Use and access is decided by the GoDeep steering board, where each center has one vote. As of April 2022, GoDeep comprised 15,742 individuals with 1.9 million data points from eight PH centers. Geographic distribution comprises 3990 enrollees (25%) from America and 11,752 (75%) from Europe. Eighty-nine perecent were diagnosed with PH and 11% were classified as not PH and provided a comparator group. The retrospective observation period is an average of 3.5 years (standard error of the mean 0.04), with 1159 PH patients followed for over 10 years. Pulmonary arterial hypertension represents the largest PH group (42.6%), followed by Group 2 (21.7%), Group 3 (17.3%), Group 4 (15.2%), and Group 5 (3.3%). The age distribution spans several decades, with patients 60 years or older comprising 60%. The majority of patients met an intermediate risk profile upon diagnosis. Data entry from a further six centers is ongoing, and negotiations with >10 centers worldwide have commenced. Using electronic interface-based automated retrospective and prospective data transfer, GoDeep aims to provide in-depth epidemiological and etiological understanding of PH and its various groups/subgroups on a global scale, offering insights for improved management. © 2022 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on beha

Published
2022

21. Aggressive Afterload Lowering to Improve the Right Ventricle A New Target for Medical Therapy in Pulmonary Arterial Hypertension?

Author

Vizza, Carmine Dario, Lang, Irene, Badagliacca, Roberto, Benza, Raymond L., Rosenkranz, Stephan, White, Richard James, Adir, Yochai, Andreassen, Arne Kristian, Balasubramanian, Vijay, Bartolome, Sonja, Blanco, Isabel, Bourge, Robert C., Carlsen, Jørn, Camacho, Rafael Enrique Conde, D'Alto, Michele, Farber, Harrison W., Frantz, Robert R.P., Ford, Hubert James, Ghio, S., Gomberg-Maitlan, Mardi, Humbert, Marc, Naeije, Robert, Orfanos, Stylianos S.E., Oudiz, Ronald J., Perrone, Sergio S.V., Shlobin, Oksana Anatolia, Simon, Marc M.A., Sitbon, Olivier, Torres, Fernando, Vachiery, Jean-Luc, Wang, Kuo Yang, Yacoub, Magdi M.H., Liu, Yan, Golden, Gil, Matsubara, Hiromi, Vizza, Carmine Dario, Lang, Irene, Badagliacca, Roberto, Benza, Raymond L., Rosenkranz, Stephan, White, Richard James, Adir, Yochai, Andreassen, Arne Kristian, Balasubramanian, Vijay, Bartolome, Sonja, Blanco, Isabel, Bourge, Robert C., Carlsen, Jørn, Camacho, Rafael Enrique Conde, D'Alto, Michele, Farber, Harrison W., Frantz, Robert R.P., Ford, Hubert James, Ghio, S., Gomberg-Maitlan, Mardi, Humbert, Marc, Naeije, Robert, Orfanos, Stylianos S.E., Oudiz, Ronald J., Perrone, Sergio S.V., Shlobin, Oksana Anatolia, Simon, Marc M.A., Sitbon, Olivier, Torres, Fernando, Vachiery, Jean-Luc, Wang, Kuo Yang, Yacoub, Magdi M.H., Liu, Yan, Golden, Gil, and Matsubara, Hiromi

Abstract

Despite numerous therapeutic advances in pulmonary arterial hypertension, patients continue to suffer high morbidity and mortality, particularly considering a median age of 50 years. This article explores whether early, robust reduction of right ventricular afterload would facilitate substantial improvement in right ventricular function and thus whether afterload reduction should be a treatment goal for pulmonary arterial hypertension. The earliest clinical studies of prostanoid treatment in pulmonary arterial hypertension demonstrated an important link between lowering mean pulmonary arterial pressure (or pulmonary vascular resistance) and improved survival. Subsequent studies of oral monotherapy or sequential combination therapy demonstrated smaller reductions in mean pulmonary arterial pressure and pulmonary vascular resistance. More recently, retrospective reports of initial aggressive prostanoid treatment or initial combination oral and parenteral therapy have shown marked afterload reduction along with significant improvements in right ventricular function. Some data suggest that reaching threshold levels for pressure or resistance (components of right ventricular afterload) may be key to interrupting the selfperpetuating injury of pulmonary vascular disease in pulmonary arterial hypertension and could translate into improved longterm clinical outcomes. Based on these clues, the authors postulate that improved clinical outcomes might be achieved by targeting significant afterload reduction with initial oral combination therapy and early parenteral prostanoids., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2022

22. Feasibility of semi-recumbent bicycle exercise Doppler echocardiography for the evaluation of the right heart and pulmonary circulation unit in different clinical conditions: the RIGHT heart international NETwork (RIGHT-NET)

Author

Ferrara F., Gargani L., Naeije R., Rudski L., Armstrong W. F., Wierzbowska-Drabik K., Argiento P., Bandera F., Cademartiri F., Citro R., Cittadini A., Cocchia R., Contaldi C., D'Alto M., D'Andrea A., Grunig E., Guazzi M., Kolias T. J., Limongelli G., Marra A. M., Mauro C., Moreo A., Ranieri B., Saggar R., Salzano A., Stanziola A. A., Vriz O., Vannan M., Kasprzak J. D., Bossone E., Capuano F., Benvenga R., Bellino M., Radano I., Marra A., D'Assante R., Rega S., Mazzola M., Raciti M., Dellegrottaglie S., De Luca N., Rozza F., Russo V., Di Salvo G., Ghio S., Guida S., Eichstaedt C. A., Labate V., La Gerche A., Pacileo G., Verrengia M., Kovacs G., Douschan P., Casadei F., De Chiara B., Ostenfeld E., Pedrizzetti G., Pieri F., Mori F., Moggi-Pignone A., Pratali L., Pugliese N., Selton-Suty C., Huttin O., Venner C., Serra W., Tafuni F., Stanziola A., Martino M., Caccavo G., Szabo I., Varga A., Agoston G., Voilliot D., Mobasseri S., Flueckiger P., Liu S., Ferrara, F., Gargani, L., Naeije, R., Rudski, L., Armstrong, W. F., Wierzbowska-Drabik, K., Argiento, P., Bandera, F., Cademartiri, F., Citro, R., Cittadini, A., Cocchia, R., Contaldi, C., D'Alto, M., D'Andrea, A., Grunig, E., Guazzi, M., Kolias, T. J., Limongelli, G., Marra, A. M., Mauro, C., Moreo, A., Ranieri, B., Saggar, R., Salzano, A., Stanziola, A. A., Vriz, O., Vannan, M., Kasprzak, J. D., Bossone, E., Capuano, F., Benvenga, R., Bellino, M., Radano, I., Marra, A., D'Assante, R., Rega, S., Mazzola, M., Raciti, M., Dellegrottaglie, S., De Luca, N., Rozza, F., Russo, V., Di Salvo, G., Ghio, S., Guida, S., Eichstaedt, C. A., Labate, V., La Gerche, A., Pacileo, G., Verrengia, M., Kovacs, G., Douschan, P., Casadei, F., De Chiara, B., Ostenfeld, E., Pedrizzetti, G., Pieri, F., Mori, F., Moggi-Pignone, A., Pratali, L., Pugliese, N., Selton-Suty, C., Huttin, O., Venner, C., Serra, W., Tafuni, F., Stanziola, A., Martino, M., Caccavo, G., Szabo, I., Varga, A., Agoston, G., Voilliot, D., Mobasseri, S., Flueckiger, P., and Liu, S.

Subjects
Adult, medicine.medical_specialty, Pulmonary Circulation, Adolescent, Ventricular Dysfunction, Right, Atrial Pressure, Population, Right heart, Predictive Value of Test, Regurgitation (circulation), 030204 cardiovascular system & hematology, Doppler echocardiography, Pulmonary hypertension, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Predictive Value of Tests, Internal medicine, medicine.artery, medicine, Ventricular outflow tract, Humans, Radiology, Nuclear Medicine and imaging, education, Cardiac imaging, Exercise Doppler echocardiography, Aged, Aged, 80 and over, education.field_of_study, medicine.diagnostic_test, business.industry, Middle Aged, medicine.disease, Echocardiography, Doppler, Bicycling, Feasibility Studie, 030228 respiratory system, Pulmonary artery, Cardiology, cardiovascular system, Ventricular Function, Right, Right ventricle, Feasibility Studies, Female, Cardiology and Cardiovascular Medicine, business, Human
Abstract

Exercise Doppler echocardiography (EDE) is a well-validated tool in ischemic and valvular heart diseases. However, its use in the assessment of the right heart and pulmonary circulation unit (RH-PCU) is limited. The aim of this study is to assess the semi-recumbent bicycle EDE feasibility for the evaluation of RH-PCU in a large multi-center population, from healthy individuals and elite athletes to patients with overt or at risk of developing pulmonary hypertension (PH). From January 2019 to July 2019, 954 subjects [mean age 54.2 ± 16.4years, range 16–96, 430 women] underwent standardized semi-recumbent bicycle EDE with an incremental workload of 25 watts every 2min, were prospectively enrolled among 7 centers participating to the RIGHT Heart International NETwork (RIGHT-NET). EDE parameters of right heart structure, function and pressures were obtained according to current recommendations. Right ventricular (RV) function at peak exercise was feasible in 903/940 (96%) by tricuspid annular plane systolic excursion (TAPSE), 667/751 (89%) by tissue Doppler-derived tricuspid lateral annular systolic velocity (S′) and 445/672 (66.2%) by right ventricular fractional area change (RVFAC). RV—right atrial pressure gradient [RV–RA gradient = 4 × tricuspid regurgitation velocity2 (TRV)] was feasible in 894/954 patients (93.7%) at rest and in 816/954 (85.5%) at peak exercise. The feasibility rate in estimating pulmonary artery pressure improved to more than 95%, if both TRV and/or right ventricular outflow tract acceleration time (RVOT AcT) were considered. In high specialized echocardiography laboratories semi-recumbent bicycle EDE is a feasible tool for the assessment of the RH-PCU pressure and function.

Published
2021

23. Imaging of Improved Right Ventricular Coupling, Risk Status and Survival in Pulmonary Arterial Hypertension

Author

Badagliacca, R., primary, Papa, S., additional, D'Alto, M., additional, Ghio, S., additional, Argiento, P., additional, Brunetti, N., additional, Casamassima, V., additional, Casu, G., additional, Cedrone, N., additional, Confalonieri, M., additional, Corda, M., additional, Correale, M., additional, D'Agostino, C., additional, De Michele, L., additional, Galgano, G., additional, Greco, A., additional, Lombardi, C., additional, Manzi, G., additional, Mercurio, V., additional, Mulè, M., additional, Paciocco, G., additional, Romaniello, A., additional, Romeo, E., additional, Scelsi, L., additional, Stolfo, D., additional, Vitulo, P., additional, Naeije, R., additional, and Vizza, C., additional

Published
2022
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25. Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood

Author

Kariotis, S, Jammeh, E, Swietlik, EM, Pickworth, JA, Rhodes, CJ, Otero, P, Wharton, J, Iremonger, J, Dunning, MJ, Pandya, D, Mascarenhas, TS, Errington, N, Thompson, AAR, Romanoski, CE, Rischard, F, Garcia, JGN, Yuan, JX-J, An, T-HS, Desai, AA, Coghlan, G, Lordan, J, Corris, PA, Howard, LS, Condliffe, R, Kiely, DG, Church, C, Pepke-Zaba, J, Toshner, M, Wort, S, Gräf, S, Morrell, NW, Wilkins, MR, Lawrie, A, Wang, D, Bleda, M, Hadinnapola, C, Haimel, M, Auckland, K, Tilly, T, Martin, JM, Yates, K, Treacy, CM, Day, M, Greenhalgh, A, Shipley, D, Peacock, AJ, Irvine, V, Kennedy, F, Moledina, S, MacDonald, L, Tamvaki, E, Barnes, A, Cookson, V, Chentouf, L, Ali, S, Othman, S, Ranganathan, L, Gibbs, JSR, DaCosta, R, Pinguel, J, Dormand, N, Parker, A, Stokes, D, Ghedia, D, Tan, Y, Ngcozana, T, Wanjiku, I, Polwarth, G, Mackenzie Ross, RV, Suntharalingam, J, Grover, M, Kirby, A, Grove, A, White, K, Seatter, A, Creaser-Myers, A, Walker, S, Roney, S, Elliot, CA, Charalampopoulos, A, Sabroe, I, Hameed, A, Armstrong, I, Hamilton, N, Rothman, AMK, Swift, AJ, Wild, JM, Soubrier, F, Eyries, M, Humbert, M, Montani, D, Girerd, B, Scelsi, L, Ghio, S, Gall, H, Ghofrani, A, Bogaard, HJ, Noordegraaf, AV, Houweling, AC, Veld, AHI, and Schotte, G

Abstract

Idiopathic pulmonary arterial hypertension (IPAH) is a rare but fatal disease diagnosed by right heart catheterisation and the exclusion of other forms of pulmonary arterial hypertension, producing a heterogeneous population with varied treatment response. Here we show unsupervised machine learning identification of three major patient subgroups that account for 92% of the cohort, each with unique whole blood transcriptomic and clinical feature signatures. These subgroups are associated with poor, moderate, and good prognosis. The poor prognosis subgroup is associated with upregulation of the ALAS2 and downregulation of several immunoglobulin genes, while the good prognosis subgroup is defined by upregulation of the bone morphogenetic protein signalling regulator NOG, and the C/C variant of HLA-DPA1/DPB1 (independently associated with survival). These findings independently validated provide evidence for the existence of 3 major subgroups (endophenotypes) within the IPAH classification, could improve risk stratification and provide molecular insights into the pathogenesis of IPAH.

Published
2021

29. Long-term outcome of patients with cardiolaminopathy undergoing defibrillator implantation: single-center experience

Author

Dusi, V, primary, Masiello, L.C, additional, Vicentini, A, additional, Savastano, S, additional, Petracci, B, additional, Sanzo, A, additional, Baldi, E, additional, Greco, A, additional, Turco, A, additional, Raineri, C, additional, Scelsi, L, additional, Ghio, S, additional, Serio, A, additional, Arbustini, E, additional, and Rordorf, R, additional

Published
2021
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30. Hadrontherapy for intra- or para-cardiac tumors: evaluation of cardiac radiation dose distribution and acute cardiac effects

Author

Dusi, V, primary, Barcellini, A, additional, Greco, A, additional, Vitolo, V, additional, Vai, A, additional, Mirandola, A, additional, Zambrino, D, additional, Roccio, M, additional, Coccia, M, additional, Turco, A, additional, Sanzo, A, additional, Vicentini, A, additional, Ghio, S, additional, Orlandi, E, additional, and Rordorf, R, additional

Published
2021
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32. Switching to riociguat versus maintenance therapy with phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension (REPLACE): a multicentre, open-label, randomised controlled trial

Author

Hoeper, Marius M, primary, Al-Hiti, Hikmet, additional, Benza, Raymond L, additional, Chang, Sung-A, additional, Corris, Paul A, additional, Gibbs, J Simon R, additional, Grünig, Ekkehard, additional, Jansa, Pavel, additional, Klinger, James R, additional, Langleben, David, additional, McLaughlin, Vallerie V, additional, Meyer, Gisela M B, additional, Ota-Arakaki, Jaquelina, additional, Peacock, Andrew J, additional, Pulido, Tomás, additional, Rosenkranz, Stephan, additional, Vizza, Carmine Dario, additional, Vonk-Noordegraaf, Anton, additional, White, R James, additional, Chang, Mikyung, additional, Kleinjung, Frank, additional, Meier, Christian, additional, Paraschin, Karen, additional, Ghofrani, Hossein Ardeschir, additional, Simonneau, Gérald, additional, Olschewski, H, additional, Delcroix, M, additional, Andrade-Lima, M, additional, de Amorim Corrêac, R, additional, Figueiredo Campos, F, additional, Ota Arakaki, J, additional, Meyer, G, additional, De Souza, R, additional, Langleben, D, additional, Al-Hiti, H, additional, Jansa, P, additional, Mellemkjær, S, additional, Bauer, F, additional, Montani, D, additional, Simonneau, G, additional, Drömann, D, additional, Ghofrani, H-A, additional, Grünig, E, additional, Halank, M, additional, Held, M, additional, Hoeper, MM, additional, Klose, H, additional, Kneidinger, N, additional, Leuchte, H, additional, Opitz, C, additional, Rosenkranz, S, additional, Wilkens, H, additional, Wirtz, H, additional, Karvounis, H, additional, Pitsiou, G, additional, Orfanos, S, additional, D'Alto, M, additional, Ghio, S, additional, Vizza, CD, additional, Vitulo, P, additional, Nakayama, T, additional, Maki, H, additional, Tatebe, S, additional, de los Rios Ibarra, M, additional, Pulido, T, additional, Van Dijk, A, additional, Vonk-Noordegraaf, A, additional, Roleder, T, additional, Castro, G, additional, Loureiro, MJ, additional, Robalo-Martins, S, additional, Barberá, JA, additional, Lázaro, M, additional, Perez-Penate, GM, additional, Román, A, additional, Cheng, C-C, additional, Hsu, C-H, additional, Hsu, H-H, additional, Atahan, E, additional, Mogulkoc Bishop, N, additional, Okumus, NG, additional, Onen, Z, additional, Chang, H-J, additional, Chang, S-A, additional, Lee, J-S, additional, Kim, H-K, additional, Coghlan, JG, additional, Corris, PA, additional, Church, AC, additional, Condliffe, R, additional, Gibbs, JSR, additional, Peacock, AJ, additional, Wort, S, additional, Allen, R, additional, Allen, S, additional, Awdish, R, additional, Benza, RL, additional, DeSouza, S, additional, Feldman, J, additional, Johri, S, additional, Klinger, JR, additional, Layish, D, additional, McConnell, J, additional, McLaughlin, VV, additional, Migliore, C, additional, Rahaghi, F, additional, Rischard, F, additional, Robbins, I, additional, Satterwhite, L, additional, Shah, T, additional, Sulica, R, additional, and White, RJ, additional

Published
2021
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33. Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood

Author

Kariotis, S, Jammeh, E, Swietlik, EM, Pickworth, JA, Rhodes, CJ, Otero, P, Wharton, J, Iremonger, J, Dunning, MJ, Pandya, D, Mascarenhas, TS, Errington, N, Thompson, AAR, Romanoski, CE, Rischard, F, Garcia, JGN, Yuan, JX-J, An, T-HS, Desai, AA, Coghlan, G, Lordan, J, Corris, PA, Howard, LS, Condliffe, R, Kiely, DG, Church, C, Pepke-Zaba, J, Toshner, M, Wort, S, Graf, S, Morrell, NW, Wilkins, MR, Lawrie, A, Wang, D, Bleda, M, Hadinnapola, C, Haimel, M, Auckland, K, Tilly, T, Martin, JM, Yates, K, Treacy, CM, Day, M, Greenhalgh, A, Shipley, D, Peacock, AJ, Irvine, V, Kennedy, F, Moledina, S, MacDonald, L, Tamvaki, E, Barnes, A, Cookson, V, Chentouf, L, Ali, S, Othman, S, Ranganathan, L, Gibbs, JSR, DaCosta, R, Pinguel, J, Dormand, N, Parker, A, Stokes, D, Ghedia, D, Tan, Y, Ngcozana, T, Wanjiku, I, Polwarth, G, Mackenzie Ross, RV, Suntharalingam, J, Grover, M, Kirby, A, Grove, A, White, K, Seatter, A, Creaser-Myers, A, Walker, S, Roney, S, Elliot, CA, Charalampopoulos, A, Sabroe, I, Hameed, A, Armstrong, I, Hamilton, N, Rothman, AMK, Swift, AJ, Wild, JM, Soubrier, F, Eyries, M, Humbert, M, Montani, D, Girerd, B, Scelsi, L, Ghio, S, Gall, H, Ghofrani, A, Bogaard, HJ, Noordegraaf, AV, Houweling, AC, Veld, AHI, Schotte, G, Kariotis, Sokratis [0000-0001-9993-6017], Pickworth, Josephine A [0000-0002-7199-364X], Rhodes, Christopher J [0000-0002-4962-3204], Wharton, John [0000-0001-8110-2575], Iremonger, James [0000-0003-3953-8812], Dunning, Mark J [0000-0002-8853-9435], Errington, Niamh [0000-0001-6768-7394], Thompson, AA Roger [0000-0002-0717-4551], Howard, Luke S [0000-0003-2822-210X], Graf, Stefan [0000-0002-1315-8873], Wilkins, Martin R [0000-0003-3926-1171], Lawrie, Allan [0000-0003-4192-9505], Wang, Dennis [0000-0003-0068-1005], Apollo - University of Cambridge Repository, Gräf, Stefan [0000-0002-1315-8873], Pickworth, Josephine A. [0000-0002-7199-364X], Rhodes, Christopher J. [0000-0002-4962-3204], Dunning, Mark J. [0000-0002-8853-9435], Thompson, A. A. Roger [0000-0002-0717-4551], Howard, Luke S. [0000-0003-2822-210X], Wilkins, Martin R. [0000-0003-3926-1171], Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Human genetics, and ACS - Atherosclerosis & ischemic syndromes

Subjects
HYPOXIA-INDUCED PROLIFERATION, OPERATED CALCIUM-ENTRY, Classification and taxonomy, Science, PROGNOSTIC IMPACT, General Physics and Astronomy, Down-Regulation, 631/114/2404, General Biochemistry, Genetics and Molecular Biology, 38/91, Functional clustering, Genomic analysis, 631/114/1386, 631/1647/2217, Humans, Familial Primary Pulmonary Hypertension, HLA-DP beta-Chains, RISK SCORE CALCULATOR, OUTCOMES, Pulmonary Arterial Hypertension, Science & Technology, Multidisciplinary, Gene Expression Profiling, 692/4019/592/75, article, 49/39, General Chemistry, Multidisciplinary Sciences, IRON-DEFICIENCY, Cardiovascular diseases, UK National PAH Cohort Study Consortium, REGISTRY, ASSESSMENTS, SURVIVAL, Science & Technology - Other Topics, Transcriptome, 5-Aminolevulinate Synthetase
Abstract

Idiopathic pulmonary arterial hypertension (IPAH) is a rare but fatal disease diagnosed by right heart catheterisation and the exclusion of other forms of pulmonary arterial hypertension, producing a heterogeneous population with varied treatment response. Here we show unsupervised machine learning identification of three major patient subgroups that account for 92% of the cohort, each with unique whole blood transcriptomic and clinical feature signatures. These subgroups are associated with poor, moderate, and good prognosis. The poor prognosis subgroup is associated with upregulation of the ALAS2 and downregulation of several immunoglobulin genes, while the good prognosis subgroup is defined by upregulation of the bone morphogenetic protein signalling regulator NOG, and the C/C variant of HLA-DPA1/DPB1 (independently associated with survival). These findings independently validated provide evidence for the existence of 3 major subgroups (endophenotypes) within the IPAH classification, could improve risk stratification and provide molecular insights into the pathogenesis of IPAH., Idiopathic pulmonary arterial hypertension is a rare and fatal disease with a heterogeneous treatment response. Here the authors show that unsupervised machine learning of whole blood transcriptomes from 359 patients with idiopathic pulmonary arterial hypertension identifies 3 subgroups (endophenotypes) that improve risk stratification and provide new molecular insights.

Published
2020
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34. Reply to Weatherald et al.

Author

Badagliacca, Roberto, D’Alto, Michele, Ghio, S., Vizza, Carmine Dario, Naeije, Robert, Badagliacca, Roberto, D’Alto, Michele, Ghio, S., Vizza, Carmine Dario, and Naeije, Robert

Abstract

SCOPUS: le.j, DecretOANoAutActif, info:eu-repo/semantics/published

Published
2021

35. Risk reduction and hemodynamics with initial combination therapy in pulmonary arterial hypertension

Author

Badagliacca, Roberto, D’Alto, Michele, Ghio, S., Argiento, P., Bellomo, Vincenzo, Brunetti, Natale Daniele, Casu, Gavino, Confalonieri, Marco, Corda, Marco, Correale, Michele, D’Agostino, Carlo, de Michele, Lucrezia, Galgano, Giuseppe, Greco, Alessandra, Lombardi, Carlo, Manzi, Giovanna, Mercurio, Valentina, Mulè, Massimiliano, Paciocco, Giuseppe, Papa, Silvia, Romeo, E., Scelsi, Laura, Stolfo, Davide, Vitulo, Patrizio, Naeije, Robert, Vizza, Carmine Dario, Badagliacca, Roberto, D’Alto, Michele, Ghio, S., Argiento, P., Bellomo, Vincenzo, Brunetti, Natale Daniele, Casu, Gavino, Confalonieri, Marco, Corda, Marco, Correale, Michele, D’Agostino, Carlo, de Michele, Lucrezia, Galgano, Giuseppe, Greco, Alessandra, Lombardi, Carlo, Manzi, Giovanna, Mercurio, Valentina, Mulè, Massimiliano, Paciocco, Giuseppe, Papa, Silvia, Romeo, E., Scelsi, Laura, Stolfo, Davide, Vitulo, Patrizio, Naeije, Robert, and Vizza, Carmine Dario

Abstract

Rationale: An initial oral combination of drugs is being recommended in pulmonary arterial hypertension (PAH), but the effects of this approach on risk reduction and pulmonary vascular resistance (PVR) are not known. Objectives: To test the hypothesis that a low-risk status would be determined by the reduction of PVR in patients with PAH treated upfront with a combination of oral drugs. Methods: The study enrolled 181 treatment-naive patients with PAH (81% idiopathic) with a follow-up right heart catheterization at 6 months (interquartile range, 144–363 d) after the initial combination of endothelin receptor antagonist 1 phosphodiesterase-5 inhibitor drugs and clinical evaluation and risk assessments by European guidelines and Registry to Evaluate Early and Long-Term PAH Disease Management scores. Measurements and Main Results: Initial combination therapy improved functional class and 6-minute-walk distance and decreased PVR by an average of 35% (median, 40%). One-third of the patients had a decrease in PVR,25%. This poor hemodynamic response was independently predicted by age, male sex, pulmonary artery pressure and cardiac index, and at echocardiography, a right/left ventricular surface area ratio of greater than 1 associated with low tricuspid annular plane systolic excursion of less than 18 mm. A low-risk status at 6 months was achieved or maintained in only 34.8% (Registry to Evaluate Early and Long-Term PAH Disease Management score) to 43.1% (European score) of the patients. Adding criteria of poor hemodynamic response improved prediction of a low-risk status. Conclusions: A majority of patients with PAH still insufficiently improved after 6 months of initial combinations of oral drugs is identifiable at initial evaluation by hemodynamic response criteria added to risk scores., SCOPUS: ar.j, DecretOANoAutActif, info:eu-repo/semantics/published

Published
2021

36. Long-term follow-up of heart transplant patients treated with permanent pacemaker: a monocentric study

Author

Tua, L, primary, Turco, A, additional, Acquaro, M, additional, Scelsi, L, additional, Greco, A, additional, Ghio, S, additional, Savastano, S, additional, Sanzo, A, additional, Vicentini, A, additional, Petracci, B, additional, Vullo, E, additional, Vicini Scajola, L, additional, Pelenghi, S, additional, Oltrona Visconti, L, additional, and Rordorf, R, additional

Published
2021
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39. Poster session: Aortic stenosis

Author

Pica, S, Ghio, S, Raineri, C, Camporotondo, R, Rordorf, R, Previtali, M, Landolina, ME, Valentini, A, Turco, A, and Visconti, LO

Published
2012

42. Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial

Author

Ponikowski, Piotr, primary, Kirwan, Bridget-Anne, additional, Anker, Stefan D, additional, McDonagh, Theresa, additional, Dorobantu, Maria, additional, Drozdz, Jarosław, additional, Fabien, Vincent, additional, Filippatos, Gerasimos, additional, Göhring, Udo Michael, additional, Keren, Andre, additional, Khintibidze, Irakli, additional, Kragten, Hans, additional, Martinez, Felipe A, additional, Metra, Marco, additional, Milicic, Davor, additional, Nicolau, José C, additional, Ohlsson, Marcus, additional, Parkhomenko, Alexander, additional, Pascual-Figal, Domingo A, additional, Ruschitzka, Frank, additional, Sim, David, additional, Skouri, Hadi, additional, van der Meer, Peter, additional, Lewis, Basil S, additional, Comin-Colet, Josep, additional, von Haehling, Stephan, additional, Cohen-Solal, Alain, additional, Danchin, Nicolas, additional, Doehner, Wolfram, additional, Dargie, Henry J, additional, Motro, Michael, additional, Butler, Javed, additional, Friede, Tim, additional, Jensen, Klaus H, additional, Pocock, Stuart, additional, Jankowska, Ewa A, additional, Azize, G, additional, Fernandez, A, additional, Zapata, GO, additional, Garcia Pacho, P, additional, Glenny, A, additional, Ferre Pacora, F, additional, Parody, ML, additional, Bono, J, additional, Beltrano, C, additional, Hershson, A, additional, Vita, N, additional, Luquez, HA, additional, Cestari, HG, additional, Fernandez, H, additional, Prado, A, additional, Berli, M, additional, García Durán, R, additional, Thierer, J, additional, Diez, M, additional, Lobo Marquez, L, additional, Borelli, RR, additional, Hominal, MÁ, additional, Metra, M, additional, Ameri, P, additional, Agostoni, P, additional, Salvioni, A, additional, Fattore, L, additional, Gronda, E, additional, Ghio, S, additional, Turrini, F, additional, Uguccioni, M, additional, Di Biase, M, additional, Piepoli, M, additional, Savonitto, S, additional, Mortara, A, additional, Terrosu, P, additional, Fucili, A, additional, Boriani, G, additional, Midi, P, additional, Passamonti, E, additional, Cosmi, F, additional, van der Meer, P, additional, Van Bergen, P, additional, van de Wetering, M, additional, Al-Windy, NYY, additional, Tanis, W, additional, Meijs, M, additional, Groutars, RGEJ, additional, The, HKS, additional, Kietselaer, B, additional, van Kesteren, HAM, additional, Beelen, DPW, additional, Heymeriks, J, additional, Van de Wal, R, additional, Schaap, J, additional, Emans, M, additional, Westendorp, P, additional, Nierop, PR, additional, Nijmeijer, R, additional, Manintveld, OC, additional, Dorobantu, M, additional, Darabantiu, DA, additional, Zdrenghea, D, additional, Toader, DM, additional, Petrescu, L, additional, Militaru, C, additional, Crisu, D, additional, Tomescu, MC, additional, Stanciulescu, G, additional, Rodica Dan, A, additional, Iosipescu, LC, additional, Serban, DL, additional, Drozdz, J, additional, Szachniewicz, J, additional, Bronisz, M, additional, Tycińska, A, additional, Wozakowska-Kaplon, B, additional, Mirek-Bryniarska, E, additional, Gruchała, M, additional, Nessler, J, additional, Straburzyńska-Migaj, E, additional, Mizia-Stec, K, additional, Szelemej, R, additional, Gil, R, additional, Gąsior, M, additional, Gotsman, I, additional, Halabi, M, additional, Shochat, M, additional, Shechter, M, additional, Witzling, V, additional, Zukermann, R, additional, Arbel, Y, additional, Flugelman, M, additional, Ben-Gal, T, additional, Zvi, V, additional, Kinany, W, additional, Weinstein, JM, additional, Atar, S, additional, Goland, S, additional, Milicic, D, additional, Horvat, D, additional, Tušek, S, additional, Udovicic, M, additional, Šutalo, K, additional, Samodol, A, additional, Pesek, K, additional, Artuković, M, additional, Ružić, A, additional, Šikić, J, additional, McDonagh, T, additional, Trevelyan, J, additional, Wong, Y-K, additional, Gorog, D, additional, Ray, R, additional, Pettit, S, additional, Sharma, S, additional, Kabir, A, additional, Hamdan, H, additional, Tilling, L, additional, Baracioli, L, additional, Nigro Maia, L, additional, Dutra, O, additional, Reis, G, additional, Pimentel Filho, P, additional, Saraiva, JF, additional, Kormann, A, additional, dos Santos, FR, additional, Bodanese, L, additional, Almeida, D, additional, Precoma, D, additional, Rassi, S, additional, Costa, F, additional, Kabbani, S, additional, Abdelbaki, K, additional, Abdallah, C, additional, Arnaout, MS, additional, Azar, R, additional, Chaaban, S, additional, Raed, O, additional, Kiwan, G, additional, Hassouna, B, additional, Bardaji, A, additional, Zamorano, J, additional, del Prado, S, additional, Gonzalez Juanatey, JR, additional, Ga Bosa Ojeda, FI, additional, Gomez Bueno, M, additional, Molina, BD, additional, Pascual Figal, DA, additional, Sim, D, additional, Yeo, TJ, additional, Loh, SY, additional, Soon, D, additional, Ohlsson, M, additional, Smith, JG, additional, Gerward, S, additional, Khintibidze, I, additional, Lominadze, Z, additional, Chapidze, G, additional, Emukhvari, N, additional, Khabeishvili, G, additional, Chumburidze, V, additional, Paposhvili, K, additional, Shaburishvili, T, additional, Parhomenko, O, additional, Kraiz, I, additional, Koval, O, additional, Zolotaikina, V, additional, Malynovsky, Y, additional, Vakaliuk, I, additional, Rudenko, L, additional, Tseluyko, V, additional, and Stanislavchuk, M, additional

Published
2020
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43. Determinants of pulmonary vascular resistance reduction with upfront oral therapy in idiopathic pulmonary arterial hypertension: relevance in risk assessment

Author

Badagliacca, R, primary, D'Alto, M, additional, Ghio, S, additional, Greco, A, additional, Papa, S, additional, Romeo, E, additional, Casu, G, additional, Corda, M, additional, Paciocco, P, additional, D'Agostino, C, additional, Galgano, G, additional, Stolfo, D, additional, Correale, M, additional, Naeije, R, additional, and Vizza, C.D, additional

Published
2020
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47. Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial

Author

Ponikowski, P. Kirwan, B.-A. Anker, S.D. McDonagh, T. Dorobantu, M. Drozdz, J. Fabien, V. Filippatos, G. Göhring, U.M. Keren, A. Khintibidze, I. Kragten, H. Martinez, F.A. Metra, M. Milicic, D. Nicolau, J.C. Ohlsson, M. Parkhomenko, A. Pascual-Figal, D.A. Ruschitzka, F. Sim, D. Skouri, H. van der Meer, P. Lewis, B.S. Comin-Colet, J. von Haehling, S. Cohen-Solal, A. Danchin, N. Doehner, W. Dargie, H.J. Motro, M. Butler, J. Friede, T. Jensen, K.H. Pocock, S. Jankowska, E.A. Azize, G. Fernandez, A. Zapata, G.O. Garcia Pacho, P. Glenny, A. Ferre Pacora, F. Parody, M.L. Bono, J. Beltrano, C. Hershson, A. Vita, N. Luquez, H.A. Cestari, H.G. Fernandez, H. Prado, A. Berli, M. García Durán, R. Thierer, J. Diez, M. Lobo Marquez, L. Borelli, R.R. Hominal, M.Á. Ameri, P. Agostoni, P. Salvioni, A. Fattore, L. Gronda, E. Ghio, S. Turrini, F. Uguccioni, M. Di Biase, M. Piepoli, M. Savonitto, S. Mortara, A. Terrosu, P. Fucili, A. Boriani, G. Midi, P. Passamonti, E. Cosmi, F. van der Meer, P. Van Bergen, P. van de Wetering, M. Al-Windy, N.Y.Y. Tanis, W. Meijs, M. Groutars, R.G.E.J. The, H.K.S. Kietselaer, B. van Kesteren, H.A.M. Beelen, D.P.W. Heymeriks, J. Van de Wal, R. Schaap, J. Emans, M. Westendorp, P. Nierop, P.R. Nijmeijer, R. Manintveld, O.C. Dorobantu, M. Darabantiu, D.A. Zdrenghea, D. Toader, D.M. Petrescu, L. Militaru, C. Crisu, D. Tomescu, M.C. Stanciulescu, G. Rodica Dan, A. Iosipescu, L.C. Serban, D.L. Drozdz, J. Szachniewicz, J. Bronisz, M. Tycińska, A. Wozakowska-Kaplon, B. Mirek-Bryniarska, E. Gruchała, M. Nessler, J. Straburzyńska-Migaj, E. Mizia-Stec, K. Szelemej, R. Gil, R. Gąsior, M. Gotsman, I. Halabi, M. Shochat, M. Shechter, M. Witzling, V. Zukermann, R. Arbel, Y. Flugelman, M. Ben-Gal, T. Zvi, V. Kinany, W. Weinstein, J.M. Atar, S. Goland, S. Milicic, D. Horvat, D. Tušek, S. Udovicic, M. Šutalo, K. Samodol, A. Pesek, K. Artuković, M. Ružić, A. Šikić, J. McDonagh, T. Trevelyan, J. Wong, Y.-K. Gorog, D. Ray, R. Pettit, S. Sharma, S. Kabir, A. Hamdan, H. Tilling, L. Baracioli, L. Nigro Maia, L. Dutra, O. Reis, G. Pimentel Filho, P. Saraiva, J.F. Kormann, A. dos Santos, F.R. Bodanese, L. Almeida, D. Precoma, D. Rassi, S. Costa, F. Kabbani, S. Abdelbaki, K. Abdallah, C. Arnaout, M.S. Azar, R. Chaaban, S. Raed, O. Kiwan, G. Hassouna, B. Bardaji, A. Zamorano, J. del Prado, S. Gonzalez Juanatey, J.R. Ga Bosa Ojeda, F.I. Gomez Bueno, M. Molina, B.D. Sim, D. Yeo, T.J. Loh, S.Y. Soon, D. Ohlsson, M. Smith, J.G. Gerward, S. Khintibidze, I. Lominadze, Z. Chapidze, G. Emukhvari, N. Khabeishvili, G. Chumburidze, V. Paposhvili, K. Shaburishvili, T. Parhomenko, O. Kraiz, I. Koval, O. Zolotaikina, V. Malynovsky, Y. Vakaliuk, I. Rudenko, L. Tseluyko, V. Stanislavchuk, M. AFFIRM-AHF investigators

Abstract

Background: Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure. Methods: AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin

Published
2020

48. Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis

Author

Rhodes, CJ, Batai, K, Bleda, M, Haimel, M, Southgate, L, Germain, M, Pauciulo, MW, Hadinnapola, C, Aman, J, Girerd, B, Arora, A, Knight, J, Hanscombe, KB, Karnes, JH, Kaakinen, M, Gall, H, Ulrich, A, Harbaum, L, Cebola, I, Ferrer, J, Lutz, K, Swietlik, EM, Ahmad, F, Amouyel, P, Archer, SL, Argula, R, Austin, ED, Badesch, D, Bakshi, S, Barnett, C, Benza, R, Bhatt, N, Bogaard, HJ, Burger, CD, Chakinala, M, Church, C, Coghlan, JG, Condliffe, R, Corris, PA, Danesino, C, Debette, S, Elliott, CG, Elwing, J, Eyries, M, Fortin, T, Franke, A, Frantz, RP, Frost, A, Garcia, JGN, Ghio, S, Ghofrani, H-A, Gibbs, JSR, Harley, J, He, H, Hill, NS, Hirsch, R, Houweling, AC, Howard, LS, Ivy, D, Kiely, DG, Klinger, J, Kovacs, G, Lahm, T, Laudes, M, Machado, RD, Ross, RV, Marsolo, K, Martin, LJ, Moledina, S, Montani, D, Nathan, SD, Newnham, M, Olschewski, A, Olschewski, H, Oudiz, RJ, Ouwehand, WH, Peacock, AJ, Pepke-Zaba, J, Rehman, Z, Robbins, I, Roden, DM, Rosenzweig, EB, Saydain, G, Scelsi, L, Schilz, R, Seeger, W, Shaffer, CM, Simms, RW, Simon, M, Sitbon, O, Suntharalingam, J, Tang, H, Tchourbanov, AY, Thenappan, T, Torres, F, Toshner, MR, Treacy, CM, Noordegraaf, A, Waisfisz, Q, Walsworth, AK, Walter, RE, Wharton, J, White, RJ, Wilt, J, Wort, SJ, Yung, D, Lawrie, A, Humbert, M, Soubrier, F, Trégouët, D-A, Prokopenko, I, Kittles, R, Gräf, S, Nichols, WC, Trembath, RC, Desai, AA, Morrell, NW, Wilkins, MR, Consortium, UK NIHR Bioresource Rare Diseases, Consortium, UK PAH Cohort Study, Consortium, US PAH Biobank, McCarthy, M, Sorbonne Université (SU), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Human genetics, ACS - Atherosclerosis & ischemic syndromes, APH - Quality of Care, and ACS - Microcirculation

Subjects
Male, Pulmonary Arterial Hypertension, Genotyping Techniques, [SDV]Life Sciences [q-bio], Genetic Variation, HLA-DP alpha-Chains, Middle Aged, Polymorphism, Single Nucleotide, Risk Assessment, Survival Analysis, Article, SOXF Transcription Factors, Humans, Female, Genetic Predisposition to Disease, HLA-DP beta-Chains, Genome-Wide Association Study, Signal Transduction
Abstract

Background Raregenetic variantscause pulmonary arterial hypertension, but the contribution of commongenetic variationto disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes. Methods We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11 744 individuals with European ancestry (including 2085 patients). One GWAS usedgenotypesfrom 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals.Cross-validationof loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration ofsurvival.All-cause mortalitywas the primary endpoint in survival analyses. Findings A locus nearSOX17(rs10103692, odds ratio 1·80 [95% CI 1·55–2·08], p=5·13 × 10–15) and a second locus inHLA-DPA1andHLA-DPB1(collectively referred to asHLA-DPA1/DPB1here; rs2856830, 1·56 [1·42–1·71], p=7·65 × 10–20) within the class II MHC region were associated with pulmonary arterial hypertension. TheSOX17locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25–1·48], p=1·69 × 10–12; and rs10103692). Functional andepigenomicdata indicate that the risk variants nearSOX17altergene regulationvia anenhanceractive inendothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reducedSOX17expression. TheHLA-DPA1/DPB1rs2856830 genotype was strongly associated with survival. Median survival fromdiagnosisin patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI 12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02–8·05]), despite similar baselinedisease severity. Interpretation This is the first study to report that common genetic variation at loci in an enhancer nearSOX17and inHLA-DPA1/DPB1is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by raremutationsinSOX17. Further studies are needed to confirm the association betweenHLA typingor rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improvesrisk stratificationin clinical practice or trials.

Published
2019
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49. Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial

Author

Ponikowski, P. Kirwan, B.-A. Anker, S.D. McDonagh, T. Dorobantu, M. Drozdz, J. Fabien, V. Filippatos, G. Göhring, U.M. Keren, A. Khintibidze, I. Kragten, H. Martinez, F.A. Metra, M. Milicic, D. Nicolau, J.C. Ohlsson, M. Parkhomenko, A. Pascual-Figal, D.A. Ruschitzka, F. Sim, D. Skouri, H. van der Meer, P. Lewis, B.S. Comin-Colet, J. von Haehling, S. Cohen-Solal, A. Danchin, N. Doehner, W. Dargie, H.J. Motro, M. Butler, J. Friede, T. Jensen, K.H. Pocock, S. Jankowska, E.A. Azize, G. Fernandez, A. Zapata, G.O. Garcia Pacho, P. Glenny, A. Ferre Pacora, F. Parody, M.L. Bono, J. Beltrano, C. Hershson, A. Vita, N. Luquez, H.A. Cestari, H.G. Fernandez, H. Prado, A. Berli, M. García Durán, R. Thierer, J. Diez, M. Lobo Marquez, L. Borelli, R.R. Hominal, M.Á. Ameri, P. Agostoni, P. Salvioni, A. Fattore, L. Gronda, E. Ghio, S. Turrini, F. Uguccioni, M. Di Biase, M. Piepoli, M. Savonitto, S. Mortara, A. Terrosu, P. Fucili, A. Boriani, G. Midi, P. Passamonti, E. Cosmi, F. van der Meer, P. Van Bergen, P. van de Wetering, M. Al-Windy, N.Y.Y. Tanis, W. Meijs, M. Groutars, R.G.E.J. The, H.K.S. Kietselaer, B. van Kesteren, H.A.M. Beelen, D.P.W. Heymeriks, J. Van de Wal, R. Schaap, J. Emans, M. Westendorp, P. Nierop, P.R. Nijmeijer, R. Manintveld, O.C. Dorobantu, M. Darabantiu, D.A. Zdrenghea, D. Toader, D.M. Petrescu, L. Militaru, C. Crisu, D. Tomescu, M.C. Stanciulescu, G. Rodica Dan, A. Iosipescu, L.C. Serban, D.L. Drozdz, J. Szachniewicz, J. Bronisz, M. Tycińska, A. Wozakowska-Kaplon, B. Mirek-Bryniarska, E. Gruchała, M. Nessler, J. Straburzyńska-Migaj, E. Mizia-Stec, K. Szelemej, R. Gil, R. Gąsior, M. Gotsman, I. Halabi, M. Shochat, M. Shechter, M. Witzling, V. Zukermann, R. Arbel, Y. Flugelman, M. Ben-Gal, T. Zvi, V. Kinany, W. Weinstein, J.M. Atar, S. Goland, S. Milicic, D. Horvat, D. Tušek, S. Udovicic, M. Šutalo, K. Samodol, A. Pesek, K. Artuković, M. Ružić, A. Šikić, J. McDonagh, T. Trevelyan, J. Wong, Y.-K. Gorog, D. Ray, R. Pettit, S. Sharma, S. Kabir, A. Hamdan, H. Tillin and Ponikowski, P. Kirwan, B.-A. Anker, S.D. McDonagh, T. Dorobantu, M. Drozdz, J. Fabien, V. Filippatos, G. Göhring, U.M. Keren, A. Khintibidze, I. Kragten, H. Martinez, F.A. Metra, M. Milicic, D. Nicolau, J.C. Ohlsson, M. Parkhomenko, A. Pascual-Figal, D.A. Ruschitzka, F. Sim, D. Skouri, H. van der Meer, P. Lewis, B.S. Comin-Colet, J. von Haehling, S. Cohen-Solal, A. Danchin, N. Doehner, W. Dargie, H.J. Motro, M. Butler, J. Friede, T. Jensen, K.H. Pocock, S. Jankowska, E.A. Azize, G. Fernandez, A. Zapata, G.O. Garcia Pacho, P. Glenny, A. Ferre Pacora, F. Parody, M.L. Bono, J. Beltrano, C. Hershson, A. Vita, N. Luquez, H.A. Cestari, H.G. Fernandez, H. Prado, A. Berli, M. García Durán, R. Thierer, J. Diez, M. Lobo Marquez, L. Borelli, R.R. Hominal, M.Á. Ameri, P. Agostoni, P. Salvioni, A. Fattore, L. Gronda, E. Ghio, S. Turrini, F. Uguccioni, M. Di Biase, M. Piepoli, M. Savonitto, S. Mortara, A. Terrosu, P. Fucili, A. Boriani, G. Midi, P. Passamonti, E. Cosmi, F. van der Meer, P. Van Bergen, P. van de Wetering, M. Al-Windy, N.Y.Y. Tanis, W. Meijs, M. Groutars, R.G.E.J. The, H.K.S. Kietselaer, B. van Kesteren, H.A.M. Beelen, D.P.W. Heymeriks, J. Van de Wal, R. Schaap, J. Emans, M. Westendorp, P. Nierop, P.R. Nijmeijer, R. Manintveld, O.C. Dorobantu, M. Darabantiu, D.A. Zdrenghea, D. Toader, D.M. Petrescu, L. Militaru, C. Crisu, D. Tomescu, M.C. Stanciulescu, G. Rodica Dan, A. Iosipescu, L.C. Serban, D.L. Drozdz, J. Szachniewicz, J. Bronisz, M. Tycińska, A. Wozakowska-Kaplon, B. Mirek-Bryniarska, E. Gruchała, M. Nessler, J. Straburzyńska-Migaj, E. Mizia-Stec, K. Szelemej, R. Gil, R. Gąsior, M. Gotsman, I. Halabi, M. Shochat, M. Shechter, M. Witzling, V. Zukermann, R. Arbel, Y. Flugelman, M. Ben-Gal, T. Zvi, V. Kinany, W. Weinstein, J.M. Atar, S. Goland, S. Milicic, D. Horvat, D. Tušek, S. Udovicic, M. Šutalo, K. Samodol, A. Pesek, K. Artuković, M. Ružić, A. Šikić, J. McDonagh, T. Trevelyan, J. Wong, Y.-K. Gorog, D. Ray, R. Pettit, S. Sharma, S. Kabir, A. Hamdan, H. Tillin

Published
2020

50. Magnetic resonance imaging of pulmonary arterial compliance after pulmonary endarterectomy

Author

Ghio, S., Crimi, Gabriele, Guida, Stefania, Valentini, Adele, Celentano, Anna, Pin, Maurizio, Raineri, Claudia, Turco, Annalisa, Scelsi, Laura, Visconti, Luigi Oltrona, Naeije, Robert, D'Armini, Andrea Maria Aria A.M., Ghio, S., Crimi, Gabriele, Guida, Stefania, Valentini, Adele, Celentano, Anna, Pin, Maurizio, Raineri, Claudia, Turco, Annalisa, Scelsi, Laura, Visconti, Luigi Oltrona, Naeije, Robert, and D'Armini, Andrea Maria Aria A.M.

Abstract

SCOPUS: ar.j, DecretOANoAutActif, info:eu-repo/semantics/published

Published
2020

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