Search

Your search keyword '"Pablo Garcia-Pavia"' showing total 30 results
Start Over Author "Pablo Garcia-Pavia" Language undetermined
30 results on '"Pablo Garcia-Pavia"'

1. Prognosis of Transthyretin Cardiac Amyloidosis Without Heart Failure Symptoms

Author

Esther Gonzalez-Lopez, Luis Escobar-Lopez, Laura Obici, Giulia Saturi, Mélanie Bezard, Sunil E. Saith, Omar F. AbouEzzeddine, Roberta Mussinelli, Christian Gagliardi, Mounira Kharoubi, Jan M. Griffin, Angela Dispenzieri, Silvia Vilches, Stefano Perlini, Simone Longhi, Silvia Oghina, Adrian Rivas, Martha Grogan, Mathew S. Maurer, Thibaud Damy, Giovanni Palladini, Claudio Rapezzi, and Pablo Garcia-Pavia

Subjects
Oncology, Cardiology and Cardiovascular Medicine
Abstract

Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly recognized as a treatable cause of heart failure (HF). Advances in diagnosis and therapy have increased the number of patients diagnosed at early stages, but prognostic data on patients without HF symptoms are lacking. Moreover, it is unknown whether asymptomatic patients benefit from early initiation of transthyretin (TTR) stabilizers.The aim of this study was to describe the natural history and prognosis of ATTR-CM in patients without HF symptoms.Clinical characteristics and outcomes of patients with ATTR-CM without HF symptoms were retrospectively collected at 6 international amyloidosis centers.A total of 118 patients (78.8% men, median age 66 years [IQR: 53.8-75 years], 68 [57.6%] with variant transthyretin amyloidosis, mean left ventricular ejection fraction 60.5% ± 9.9%, mean left ventricular wall thickness 15.4 ± 3.1 mm, and 53 [45%] treated with TTR stabilizers at baseline or during follow-up) were included. During a median follow-up period of 3.7 years (IQR: 1-6 years), 38 patients developed HF symptoms (23 New York Heart Association functional class II and 14 functional class III or IV), 32 died, and 2 required cardiac transplantation. Additionally, 20 patients received pacemakers, 13 developed AF, and 1 had a stroke. Overall survival was 96.5% (95% CI: 91%-99%), 90.4% (95% CI: 82%-95%), and 82% (95% CI: 71%-89%) at 1, 3, and 5 years, respectively. Treatment with TTR stabilizers was associated with improved survival (HR: 0.31; 95% CI: 0.12-0.82;After a median follow-up period of 3.7 years, 1 in 3 patients with asymptomatic ATTR-CM developed HF symptoms, and nearly as many died or required cardiac transplantation. Treatment with TTR stabilizers was associated with improved prognosis.

Published
2022

2. Critical Comparison of Documents From Scientific Societies on Cardiac Amyloidosis

Author

Claudio Rapezzi, Alberto Aimo, Matteo Serenelli, Andrea Barison, Giuseppe Vergaro, Claudio Passino, Giorgia Panichella, Gianfranco Sinagra, Marco Merlo, Marianna Fontana, Julian Gillmore, Candida Cristina Quarta, Mathew S. Maurer, Michelle M. Kittleson, Pablo Garcia-Pavia, and Michele Emdin

Subjects
Cardiology and Cardiovascular Medicine
Published
2022

3. Natural History of MYH7-Related Dilated Cardiomyopathy

Author

Fernando de Frutos, Juan Pablo Ochoa, Marina Navarro-Peñalver, Annette Baas, Jesper Vandborg Bjerre, Esther Zorio, Irene Méndez, Rebeca Lorca, Job A.J. Verdonschot, Pablo Elpidio García-Granja, Zofia Bilinska, Diane Fatkin, M. Eugenia Fuentes-Cañamero, José M. García-Pinilla, María I. García-Álvarez, Francesca Girolami, Roberto Barriales-Villa, Carles Díez-López, Luis R. Lopes, Karim Wahbi, Ana García-Álvarez, Ibon Rodríguez-Sánchez, Javier Rekondo-Olaetxea, José F. Rodríguez-Palomares, María Gallego-Delgado, Benjamin Meder, Milos Kubanek, Frederikke G. Hansen, María Alejandra Restrepo-Córdoba, Julián Palomino-Doza, Luis Ruiz-Guerrero, Georgia Sarquella-Brugada, Alberto José Perez-Perez, Francisco José Bermúdez-Jiménez, Tomas Ripoll-Vera, Torsten Bloch Rasmussen, Mark Jansen, Maria Sabater-Molina, Perry M. Elliot, Pablo Garcia-Pavia, Eva Cabrera-Romero, Marta Cobo-Marcos, Luis Escobar-Lopez, Fernando Domínguez, Esther González-López, Juan Ramón Gimeno-Blanes, Dennis Dooijes, Bernabé López Ledesma, Inés Roche Fortea, Javier Bermejo, Maria Angeles Espinosa, Ana Isabel Fernández, Silvia Vilches, Cristina Gómez, Juan Gómez, Eliecer Coto, José Julián Rodríguez Reguero, S.R.B. Heymans, H.G. Brunner, Javier López-Díaz, Grażyna Truszkowska, Rafal Ploski, Przemysław Chmielewski, Renee Johnson, Ainhoa Robles-Mezcua, Arancha Díaz-Expósito, Alejandro I. Pérez-Cabeza, Clara Jiménez-Rubio, Vicente Climent Payá, Silvia Favilli, Petros Syrris, Douglas Cannie, Clarisse Billon, Angela Lopez-Sainz, Margarita Calvo, Ángela Cacicedo Fernández de Bobadilla, Jose Juan Onaindia-Gandarias, Larraitz Gaztañaga-Arantzamendi, Estibaliz Zamarreño-Golvano, Javier Limeres, Laura Gutiérrez-García, Eduardo Villacorta, Jan Haas, Alice Krebsova, Jens Mogensen, Sergi Cesar, Oscar Campuzano, Raúl Franco Gutiérrez, Jorge Alvarez-Rubio, David Cremer-Luengos, Guido Antoniutti, Fiama Caimi-Martinez, Rosa Macías, Juan Jiménez-Jáimez, María Luisa Peña-Peña, Salvador Lucas Díez-Aja López, Tania Pino Acereda, Blanca Arnáez Corada, Jesús Piqueras-Flores, Martin Negreira-Caamaño, Jorge Martinez-del Río, María Victoria Mogollón Jiménez, Elena Villanueva, José Luis Gonzáles, Adrián Fernández, Ulises Toscanini, Lilian E. Favaloro, Carlota Hernández Díez, MUMC+: DA KG Lab Bedrijfsbureau (9), MUMC+: DA KG AIOS (9), RS: Carim - H02 Cardiomyopathy, Instituto de Salud Carlos III, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Ministerio de Ciencia e Innovación (España), Fundación ProCNIC, Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España), European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart, ERA-CVD framework, Dutch Heart Foundation, Victor Chang Cardiac Research Institute, NSW Health, Clinical Academic Research Partnerships (CARP), Deutsches Zentrum für Herz-Kreislauf-Forschung (German Center for Cardiovascular Research), Informatics for Life (Klaus Tschira Foundation), Ministry of Health, Czech Republic, and Institute for Clinical and Experimental Medicine–IKEM

Subjects
Adult, Cardiomyopathy, Dilated, Heart Failure, Male, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Myocardiopathies, Adolescent, Myosin Heavy Chains, Ventricular Remodeling, Miocardiopaties, Arrhythmias, Cardiac, Middle Aged, dilated cardiomyopathy, Young Adult, Phenotype, MYH7, Genetics, Humans, Female, genetics, Cardiology and Cardiovascular Medicine, Cardiac Myosins, Genètica
Abstract

Instituto de Salud Carlos III (ISCIII), European Regional Development Fund/European Social Fund "A way to make Europe"/" Investing in your future" [PI18/0004, PI20/0320, PT17/0015/0043]; ISCIII; MCIN; Pro-CNIC Foundation; Severo Ochoa Centers of Excellence program [CEX2020-001041-S]; ISCIII [CM20/00101], Frutos F. de, Ochoa JP, Navarro-Peñalver M, Baas A, Bjerre JV, Zorio E, Méndez I, Lorca R, Verdonschot JAJ, García-Granja PE, Bilinska Z, Fatkin D, Fuentes-Cañamero ME, García-Pinilla JM, García-Álvarez MI, Girolami F, Barriales-Villa R, Díez-López C, Lopes LR, Wahbi K, García-Álvarez A, Rodríguez-Sánchez I, Rekondo-Olaetxea J, Rodríguez-Palomares JF, Gallego-Delgado M, Meder B, Kubanek M, Hansen FG, Restrepo-Córdoba MA, Palomino-Doza J, Ruiz-Guerrero L, Sarquella-Brugada G, Perez-Perez AJ, Bermúdez-Jiménez FJ, Ripoll-Vera T, Rasmussen TB, Jansen M, Sabater-Molina M, Elliot PM, Garcia-Pavia P; European Genetic Cardiomyopathies Initiative Investigators

Published
2022

4. 77 HELIOS-A: 18-MONTH EXPLORATORY CARDIAC RESULTS FROM THE PHASE 3 STUDY OF VUTRISIRAN IN PATIENTS WITH HEREDITARY TRANSTHYRETIN-MEDIATED AMYLOIDOSIS

Author

Roberta Mussinelli(on Behalf Of The Authors), Pablo Garcia-pavia, Julian D Gillmore, Parag Kale, John L Berk, Mathew S Maurer, Isabel Conceição, Marcelo Dicarli, Scott Solomon, Chongshu Chen, Seth Arum, John Vest, and Martha Grogan

Subjects
Cardiology and Cardiovascular Medicine
Abstract

Background Hereditary transthyretin-mediated (hATTR) amyloidosis, also known as ATTRv amyloidosis, is a fatal, multisystem disease that presents with progressive polyneuropathy and/or cardiomyopathy. HELIOS-A (NCT03759379) assessed the efficacy of vutrisiran, an investigational RNA interference therapeutic, in patients with hATTR amyloidosis with polyneuropathy. Purpose To evaluate the effect of 18 months of vutrisiran treatment on exploratory cardiac endpoints in the HELIOS-A Phase 3 study. Methods Patients were randomised (3:1) to vutrisiran (25 mg SC, q3m) or patisiran (0.3 mg/kg IV, q3w), a reference comparator. The APOLLO placebo group (n=77) was an external control. Primary endpoint was change from baseline in the modified Neuropathy Impairment Score +7 (mNIS+7) at 9 months, vs. external placebo. Exploratory cardiac endpoints included change from baseline in NT-proBNP levels, echocardiography parameters, and technetium (Tc) scintigraphy parameters at 18 months. A prespecified cardiac subpopulation was included (baseline left ventricular wall thickness ≥1.3 cm and no medical history of aortic valve disease or hypertension). Results HELIOS-A enrolled 164 patients and the primary endpoint was met. In the cardiac subpopulation (n=40/122 vutrisiran; n=36/77 placebo), 18 months of vutrisiran treatment significantly improved NT-ProBNP levels vs. external placebo (adjusted geometric fold change ratio: 0.49; p=0.0004) and demonstrated a trend towards improvement in echocardiographic parameters vs. external placebo (including a significant difference in cardiac output [least squares mean difference: 0.41; p=0.043]). Of the 122 vutrisiran-treated patients, 99mTc scintigraphy assessment was captured for 64 vutrisiran-treated patients at baseline, 35 (54.7%) of whom had Perugini grade ≥2 (moderate/intense) cardiac uptake of 99mTc. Among patients with evaluable scintigraphy parameters repeated at 18 months (evaluable patients), heart-to-contralateral lung ratio and normalised LV total uptake on scintigraphy improved (decrease from baseline) in 64.6% (31/48) and 68.1% (32/47), respectively, at 18 months. Of the evaluable patients, 28.1% (16/57) had an improvement (reduction from baseline) in Perugini grade of cardiac uptake, 68.4% (39/57) had no change in grade, and 3.5% (2/57) worsened in grade. Of evaluable patients with baseline Perugini grade ≥2, the proportion with improvement in heart-to-contralateral lung ratio and normalised LV total uptake was 76.9% (20/26) and 100% (25/25) respectively. No cardiac safety concerns were identified with vutrisiran treatment. Conclusions In this exploratory analysis, vutrisiran treatment was associated with a positive impact on NT-ProBNP levels and echocardiographic parameters vs. external placebo in the cardiac subpopulation. Vutrisiran treatment also reduced cardiac uptake of 99mTc potentially suggesting reduction in cardiac amyloid, although the clinical significance of this is not yet clear.

Published
2022

7. Changing paradigm in the treatment of amyloidosis: From disease-modifying drugs to anti-fibril therapy

Author

C. Cristina Quarta, Marianna Fontana, Thibaud Damy, Julia Catini, Damien Simoneau, Michele Mercuri, Pablo Garcia-Pavia, Mathew S. Maurer, and Giovanni Palladini

Subjects
Cardiology and Cardiovascular Medicine
Abstract

Cardiac amyloidosis is a rare, debilitating, and usually fatal disease increasingly recognized in clinical practice despite patients presenting with non-specific symptoms of cardiomyopathy. The current standard of care (SoC) focuses on preventing further amyloid formation and deposition, either with anti-plasma cell dyscrasia (anti-PCD) therapies in light-chain (AL) amyloidosis or stabilizers of transthyretin (TTR) in transthyretin amyloidosis (ATTR). The SoC is supplemented by therapies to treat the complications arising from organ dysfunction; for example, heart failure, arrhythmia, and proteinuria. Advancements in treatments have improved patient survival, especially for those whose disease is detected and for whom treatment is initiated at an early stage. However, there still are many unmet medical needs, particularly for patients with severe disease for whom morbidity and mortality remain high. There currently are no approved treatments to reverse amyloid infiltration and deplete the amyloid fibrils already deposited in organs, which can continue to cause progressive dysfunction. Anti-fibril therapies aimed at removing the deposited fibrils are being investigated for safety and efficacy in improving outcomes for patients with severe disease. However, there is no clinical evidence yet that removing deposited amyloid fibrils will improve organ function, thereby improving quality of life or extending life. Nevertheless, anti-fibril therapies are actively being investigated in clinical trials to evaluate their ability to complement and synergize with current SoC.

Published
2022

8. Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy

Author

Martin S. Maron, Ahmad Masri, Lubna Choudhury, Iacopo Olivotto, Sara Saberi, Andrew Wang, Pablo Garcia-Pavia, Neal K. Lakdawala, Sherif F. Nagueh, Florian Rader, Albree Tower-Rader, Aslan T. Turer, Caroline Coats, Michael A. Fifer, Anjali Owens, Scott D. Solomon, Hugh Watkins, Roberto Barriales-Villa, Christopher M. Kramer, Timothy C. Wong, Sharon L. Paige, Stephen B. Heitner, Stuart Kupfer, Fady I. Malik, Lisa Meng, Amy Wohltman, and Theodore Abraham

Subjects
Heart Failure, Humans, Cardiomyopathy, Hypertrophic, Cardiology and Cardiovascular Medicine, Ventricular Outflow Obstruction
Abstract

Left ventricular outflow tract (LVOT) obstruction is a major determinant of heart failure symptoms in obstructive hypertrophic cardiomyopathy (oHCM). Aficamten, a next-in-class cardiac myosin inhibitor, may lower gradients and improve symptoms in these patients.This study aims to evaluate the safety and efficacy of aficamten in patients with oHCM.Patients with oHCM and LVOT gradients ≥30 mm Hg at rest or ≥50 mm Hg with Valsalva were randomized 2:1 to receive aficamten (n = 28) or placebo (n = 13) in 2 dose-finding cohorts. Doses were titrated based on gradients and ejection fraction (EF). Safety and changes in gradient, EF, New York Heart Association functional class, and cardiac biomarkers were assessed over a 10-week treatment period and after a 2-week washout.From baseline to 10 weeks, aficamten reduced gradients at rest (mean difference: -40 ± 27 mm Hg, and -43 ± 37 mm Hg in Cohorts 1 and 2, P = 0.0003 and P = 0.0004 vs placebo, respectively) and with Valsalva (-36 ± 27 mm Hg and -53 ± 44 mm Hg, P = 0.001 and 0.0001 vs placebo, respectively). There were modest reductions in EF (-6% ± 7.5% and -12% ± 5.9%, P = 0.007 and P0.0001 vs placebo, respectively). Symptomatic improvement in ≥1 New York Heart Association functional class was observed in 31% on placebo, and 43% and 64% on aficamten in Cohorts 1 and 2, respectively (nonsignificant). With aficamten, N-terminal pro-B-type natriuretic peptide was reduced (62% relative to placebo, P = 0.0002). There were no treatment interruptions and adverse events were similar between treatment arms.Aficamten resulted in substantial reductions in LVOT gradients with most patients experiencing improvement in biomarkers and symptoms. These results highlight the potential of sarcomere-targeted therapy for treatment of oHCM.

Published
2022

9. GARFIELD-AF: risk profiles, treatment patterns and 2-year outcomes in patients with atrial fibrillation in Germany, Austria and Switzerland (DACH) compared to 32 countries in other regions worldwide

Author

Haas, S., Camm, J.A., Harald, D., Steffel, J., Virdone, S., Pieper, K., Brodmann, M., Schellong, S., Misselwitz, F., Kayani, G., Kakkar, A.K., Jean-Pierre, B., John Camm, A., Fitzmaurice, D.A., Fox, K.A.A., Gersh, B.J., Goldhaber, S.Z., Shinya, G., Sylvia, H., Werner, H., Mantovani, L.G., Frank, M., Pieper, K.S., Turpie, A.G.G., Martin van Eickels, Verheugt, F.W.A., Fox Bernard, K.A.A., Gersh, J., Hector, L., Luciardi Harry Gibbs, Marianne, B., Frank, C., Antonio Carlos Pereira Barretto, Connolly, S.J., John, E., Ramon, C., Zhi-Cheng, J., Petr, J., Jørn Dalsgaard Nielsen, Hany, R., Pekka, R., Jean-Yves Le Heuzey, Matyas, K., Jitendra Pal Singh Sawhney, Giancarlo, A., Giuseppe, A., Yukihiro, K., Carlos Jerjes Sánchez Díaz, Hugo Ten Cate, Dan, A., Janina, S., Elizaveta, P., Toon Wei Lim, Barry, J., Seil, O., Xavier, V., Marten, R., Jan, S., Pantep, A., Ali, O., Alex, P., Wael Al Mahmeed, David, F., Samuel, Z.G., Dayi Hu Kangning Chen, Yusheng, Z., Huaiqin, Z., Jiyan, C., Shiping, C., Daowen, W., Yuejin, Y., Weihua, L., Hui, L., Yuehui, Y., Guizhou, T., Ping, Y., Yingmin, C., Shenghu, H., Yong, W., Guosheng, F., Xin, L., Tongguo, W., Xiaoshu, C., Xiaowei, Y., Ruiping, Z., Moshui, C., Longgen, X., Ping, C., Yang, J., Ying, G., Xue, L., Zhiming, Y., Praveen Jadhavm Raghava Sarma, Govind, K., Prakash, C., Rasesh Atulbhai Pothiwala, Mohanan Padinhare Purayil, Kamaldeep, C., Veerappa Annasaheb Kothiwale, Bagirath, R., Vinod Madan Vijan, Jitendra, S., Ganapathi, B., Aziz, K., Ramdhan, M., Manojkumar, C., Sunitha, A., Vikas, B., Govindan, V., Debabrata, R., Rajashekhar, D., G Ravi Shankar, A., Sunil, K., Dinesh, J., Kartikeya, B., Vinay, K., Udigala Madappa Nagamalesh, Rajeeve Kumar Rajput, Yukihiro Koretsune Seishu Kanamori, Kenichi, Y., Koichiro, K., Yosuke, K., Keiki, Y., Fumitoshi, T., Yuji, M., Ikuo, M., Hiroo, N., Shinichi, A., Tetsuro, S., Masahiro, M., Hiroyuki, O., Susumu, A., Kei, C., Hiroaki, N., Makoto, T., Takeshi, K., Kunihiko, Y., Hiroshi, A., Takayuki, H., Megumi, O., Shiro, A., Shinichiro, K., Kenshi, K., Takashi, M., Jun, M., Yurika, O., Ryuji, S., Kazuo, G., Kotaro, M., Yoshikuni, H., Hisakazu, S., Hiroo, M., Hitoshi, K., Tsugihiro, N., Tadashi, N., Hidekazu, N., Ryuji, Z., Yoshihisa, F., Akira, Y., Hiroyuki, N., Jun, O., Yasuyuki, K., Kinshiro, M., Yutaka, W., Masanori, Y., Hiromitsu, M., Sumihisa, A., Hajime, K., Satoru, T., Katsumi, S., Hiroki, T., Ichiro, O., Takashi, K., Satoshi, H., Masamichi, G., Takuma, E., Hidetoshi, C., Kazuaki, F., Yuhei, S., Hirokuni, S., Toshihisa, N., Yoshihiko, A., Toshiro, N., Kazuhisa, S., Fumihiro, H., Naoto, Y., Masahiro, K., Toshifumi, T., Munesumi, I., Yoshitake, F., Daisuke, I., Taku, S., Tetsu, I., Norio, I., Koichi, O., Keizo, T., Yutaka, H., Motoshi, T., Hiroto, T., Shinjiro, N., Masaaki, I., Yuichiro, N., Naomasa, M., Ashida, K., Jun, A., Seishiro, M., Osamu, A., Shuji, F., Hirofumi, M., Kazuya, M., Yoshiki, H., Ichiro, S., Kotaro, O., Ichiro, T., Mitsuyuki, A., Toshihide, U., Yoshinori, G., Makoto, I., Shoji, M., Shigeru, M., Hideo, D., Mitsuru, T., Takaaki, K., Shigeo, K., Chiga, O., Masaki, S., Masami, N., Yutaka, K., Yoichi, N., Hiroshi, O., Rikimaru, O., Masato, A., Teruaki, M., Kazuhiko, N., Takafumi, M., Junichi, M., Mitsunori, A., Masako, F., Makoto, O., Tsuneo, F., Toshiya, T., Tenei, K., Hiroshi, K., Mizuho, I., Masahiro, A., Takashi, U., Hironori, O., Masahiko, I., Yoshiki, K., Atsuyuki, N., Shinobu, T., Mitsuhiro, S., Masayuki, N., Kenichiro, I., Motoyuki, I., Taro, M., Masamichi, W., Hiroaki, M., Masato, M., Fumio, O., Teruaki, K., Kuniaki, T., Masaaki, T., Morio, I., Hiroshi, W., Toshihiko, S., Shinya, H., Hiroaki, H., Mitsumoto, H., Michitaka, H., Koichi, M., Hideki, H., Nobuyoshi, S., Yukio, S., Akira, S., Kazuo, N., Tetsuro, Y., Kunio, A., Sen, A., Chiei, T., Saori, M., Hirofumi, K., Masanori, K., Shiro, N., Atsushi, T., Shuta, T., Kazuyuki, S., Akiko, M., Hiroki, S., Jin, N., Taketo, H., Takash, I., Kazuki, S., Kazuya, K., Tomobumi, K., Tsuyoshi, T., Hirosumi, S., Kiyoshi, N., Kenichi, I., Kazuo, M., Tomohiro, S., Takeshi, I., Koichi, K., Hiromichi, K., Tsutomu, T., Mamoru, H., Jisho, K., Akitoshi, S., Yoshihiro, T., Tetsuo, B., Koji, H., Masaaki, H., Koichi, H., Takao, B., Kazuaki, M., Toshihiko, K., Kunihiko, H., Toshihide, K., Akira, N., Eiji, O., Takashi, S., Hiroyoshi, H., Chikako, S., Takashi, Y., Ichiro, M., Kazunori, S., Isamu, N., Ken, T., Osamu, I., Koichi, T., Samu, U., Hirokazu, K., Takuya, O., Seizo, O., Junya, K., Toshihiko, N., Itaru, M., Yoshifusa, M., Yasuyuki, M., Kazuo, T., Hajime, H., Tetsutaro, K., Koji, M., Masaichi, N., Takashi, W., Tomoki, Y., Masato, S., Hidekazu, A., Hisanori, S., Hiroyuki, T., Nobufusa, F., Akira, O., Kentaro, Y., Kenji, A., Taku, Y., Takeaki, K., Shunji, S., Shu, S., Nitaro, S., Masayuki, W., Yosuke, N., Toru, A., Masaki, O., Tetsushi, W., Tomoko, K., Yasuo, S., Takeshi, T., Yoshihito, H., Shinichi, H., Yukihiko, A., Yoshihiro, S., Hirohide, U., Hiroshi, T., Shuichi, T., Naoto, H., Seiichi, M., Hisashi, S., Takuma, A., Yasunobu, S., Yawara, N., Osamu, M., Hideko, I., Katsumasa, N., Masatsugu, N., Kazuo, S., Toshiyuki, F., Nobuhisa, I., Shunichi, N., Kiyoharu, S., Yujin, S., Naoko, O., Teruhiko, K., Hideaki, O., Masato, E., Tsutomu, G., Makoto, H., Emiko, N., Noriyuki, N., Toshizumi, M., Shuichi, S., Katsuhiro, O., Yoko, E., Tsuyoshi, F., Haruhiko, D., Shuichi, K., Sho, N., Yuya, U., Tetsuro, F., Mitsuru, I., Takuo, O., Shunsuke, T., Hideo, I., Norihiko, S., Kiyomitsu, I., Nobuo, W., Masatake, A., Junji, D., Tetsuya, K., Masato, T., Naoya, M., Yasuaki, F., Wataru, F., Susumu, S., Akinori, F., Ryosai, N., Hiroyasu, K., Rei, F., Keijiro, N., Yoji, K., Junya, A., Kiyoshi, Y., Toshio, A., Yasuhiro, S., Tatsuo, H., Yuichiro, K., Yasuhide, S., Yukihiro, S., Shingo, M., Kojuro, M., Yasuko, S., Toyoshi, S., Fumiko, I., Toshiyuki, K., Jaeyoung, K., Hiroshi, Y., Yoichi, T., Yoko Onuki Pearce, Yasuyuki, S., Takayuki, F., Toru, N., Hideaki, K., Yoshiyuki, K., Tetsuji, I., Hironori, M., Yasufumi, M., Masahito, S., Shimato, O., Yutaka, O., Satoshi, U., Kojiro, K., Tatsuo, O., Naoki, M., Koichi, I., Atsushi, I., Tomohiro, Y., Toshihiro, G., Tsukasa, K., Atsushi, S., Etsuo, M., Toshio, T., Hiroshi, S., Shunichi, F., Tomohiro, K., Yoshiyuki, F., Hiroshi, H., Jun, N., Kiichiro, Y., Takuya, I., Takafumi, A., Chi Keong Ching Toon Wei Lim, Kelvin, W., Tan, Y., Seil Oh Hui Nam Park, Woo-Shik, K., Hyeyoung, L., Sung-Won, J., Dae Hyeok Kim, Jun, K., Dongryeol, R., Jaemin, S., Dae-Kyeong, K., Dong Ju Choi, Yong Seog Oh, Myeong-Chan, C., Hack-Lyoung, K., Hui-Kyung, J., Dong-Gu, S., Sang Weon Park, Hoon Ki Park, Sang-Jin, H., Jung Hoon Sung, Hyung-Wook, P., Gi-Byoung, N., Young Keun On, Hong Euy Lim, Jaejin, K., Tae-Joon, C., Taek Jong Hong, Seong Hoon Park, Jung Han Yoon, Nam-Ho, K., Kee-Sik, K., Byung Chun Jung, Gyo-Seung, H., Chong-Jin, K., Sakda Rungaramsin Peerapat Katekangplu, Porames, K., Thanita, B., Wanwarang, W., Pinij, K., Khanchai, S., Waraporn, T., Supalerk, P., Khanchit, L., Doungrat, C., Warangkana, B., Sirichai, C., Songkwan, S., Pisit, H., Seksan, C., Pairoj, C., Boonsert, C., Yingsak, S., Khompiya, K., Piya, M., Sasivimon, J., Ongkarn, K., Armagan Altun Ali Aydinlar, Ramazan, T., Zeki, O., Sadik, A., Durmus Yildiray Sahin, Ozcan, Y., Mehmet Birhan Yilmaz, Hasan, P., Mesut, D., Murat, S., Levent, S., Murat, E., Ertugrul, O., Dursun, A., Florencia Rolandi Adrian Cesar Ingaramo, Gustavo Alberto Sambadaro, Vanina Fernandez Caputi, Sofia Graciela Berman, Pablo, D., Andres Javier Kleiban, Nestor, C., Rodolfo Andres Ahuad Guerrero, Leonel Adalberto Di Paola, Ricardo Dario Dran, Javier, E., Matias Jose Fosco, Victor Alfredo Sinisi, Luis Rodolfo Cartasegna, Oscar Gomez Vilamajo, Jose Luis Ramos, Sonia, S., Gerardo, Z., Diego, C., Guillermo, G., Alberto Alfredo Fernandez, Mario Alberto Berli, Fabian, F., Dário Celestino Sobral Filho Jefferson Jaber, Luciana Vidal Armaganijan, Costantino Roberto Frack Costantini, André, S., Weimar Kunz Sebba Barroso de Souzaem, João David de Souza Neto, José Márcio Ribeiro, Marcelo Silveira Teixeira, Paulo, R., Leonardo, P., Daniel, M., José Carlos Moura Jorge, Adalberto Menezes Lorga Filho, Luiz, B., Marcelo Westerlund Montera, Carlos Henrique Del Carlo, Jamil Abdalla Saad, Fernando Augusto Alves da Costa, Renato, L., Gilson Roberto de Araújo, Euler Roberto Manenti, Jose Francisco Kerr Saraiva, João Carlos Ferreira Braga, Alexandre, N., Carlos, M., Dalton, P., Fernando, R., Gilmar, R., Roberto Álvaro Ramos Filho, Estêvão Lanna Figueiredo, Roberto Vieira Botelho, Cláudio Munhoz da Fontoura Tavares, Helius Carlos Finimundi, Adriano, K., César Cássio Broilo França, Fábio, A., Guido Bernardo Aranha Rosito, João Batista de Moura Xavier Moraes Junior, Rogério Tadeu Tumelero, Lilia, M., Roberto Simões de Almeida, Ney Carter do Carmo Borges, Luís Gustavo Gomes Ferreira, Ramón Corbalán Benjamin Aleck Joseh Stockins Fernandez, Humberto, M., Fernando, L., Martín Larico Gómez, Carlos, A., Carlos, C., Patricio Marin Cuevas, Alejandro, F., Claudio Bugueño Gutiérrez, Juan, A., Sergio Potthoff Cardenas, German, E., Cesar, H., Carlos, R., Germán, A., Gustavo Charme Vilches, Carlos Jerjes Sanchez Diaz Jesus Jaime Illescas Diaz, Raul Leal Cantu, Maria Guadalupe Ramos Zavala, Ricardo Cabrera Jardines, Nilda Espinola Zavaleta, Enrique Lopez Rosas, Guillermo Antonio Llamas Esperón, Gerardo, P., Ernesto Cardona Muñoz, Norberto Matadamas Hernandez, Adolfo Leyva Rendon, Norberto Garcia Hernandez, Manuel de Los Rios Ibarra, Luis Ramon Virgen Carrillo, David Lopez Villezca, Carlos Hernandez Herrera, Juan Jose Lopez Prieto, Rodolfo Gaona Rodriguez, Efrain Villeda Espinosa, David Flores Martinez, Jose Velasco Barcena, Omar Fierro Fierro, Ignacio Rodriguez Briones, Jose Luis Leiva Pons, Humberto Alvarez Lopez, Rafael Olvera Ruiz, Carlos Gerardo Cantu Brito, Eduardo Julian Jose Roberto Chuquiure Valenzuela, Roxana Reyes Sanchez, Alberto Esteban Bazzoni Ruiz, Oscar Martin Lopez Ruiz, Roberto Arriaga Nava, Jesus David Morales Cerda, Pedro Fajardo Campos, Mario Benavides Gonzalez, Marianne Brodmann Kurt Lenz, Claus, H., Johannes, F., Heinz, D., Kurt, H., Andrea, P., Michael, W., Bruno, S., Alfons, G., Wilfried, L., Sabine, E., Peter, K., Josef, S., Heribert, R., Bernhard, S., Luc Capiau Geert Vervoort, Bart, W., Geert, H., Jan, V., Dirk, F., Yohan, B., Marc, D., Olivier, X., Harry, S., John, T., Georges, M., Wim, A., Ivan, B., Michel, B., Stefan, V., Peter, V., Philippe, P., Pascal, G., Tim, B., Philippe, D., Alex, H., Joeri, V., Axel De Wolf Eva Zidkova Petr Jansky, Rudolf, S., Vilma, M., Ondrej, L., Josef, O., Lubos, K., Blazej, R., Richard, F., Jan, H., Ilja, K., Zdenek, M., Hana, B., Ondrej, J., Jana, P., Iveta, P., Vratislav, D., Michaela, H., Petr, P., Petr, R., Jindrich, S., Miroslav, N., Vaclav, D., Katarina, P., Jiri, L., Jørn Nielsen Steen Husted, Helena, D., Ulrik, H., Søren, R., Næstved, S., Arne, B., John, M., Jan, B., Jorgen, S., Ebbe, E., Thomas, L., Michael, B., Jacob, M., Morten, S., Michael, O., Pekka Raatikainen Carmela Viitanen, Franck Paganelli Joël Ohayon, Frédéric, C., Michel, G., Yannick, G., Philippe, L., Jean-Joseph, M., Mohamed Bassel Koujan, André, M., Sylvain, D., Olivier, P., Nicolas, D., Jean-Pierre, C., Maxime, G., Dominique, G., G Lokesh, A., Mathieu, Z., Pierre, A., Emmanuel, E., James, K., Pierre-Yves, F., Jean-Pierre, H., Nestor, L., Gilles, R., Igor, S., Jean-Philippe, N., Marie Hélène Mahagne, Antoine, M., Marc, B., Jean-Baptiste, C., Vincent, N., Frederic, S., Gilles, M., Jean-Paul, B., Bernard, D., Michel, M., Désiré, O., Bernard, C., Joseph, M., Etienne, B., Jean Philippe Brugnaux, Alain, F., Pierre, N., Jean-Baptiste, B., Sebastien Schellong Harald Darius, Georg, K., Andreas, K., Uwe, G., Bernd-Thomas, K., Thomas, S., Jan, P., Enno, E., Heinz-Dieter, Z., Peter, R., Christoph, A., Gerd-Ulrich, H., Holger, M., Andreas, P., Stefan, Z., Wolfgang, E., Guenter, R., Dirk, G., Norbert, L., Petra, S., Henning, W., Cosmas, W., Steffen, S., Toralf, S., Adyeri, B., Maximilian, K., Hans-Hermann, Z., Friedhelm, K., Andreas, C., Sabine, O., Torsten, L., Hermann-Josef, H., Gunter, L., Hans-Walter, B., Gunter, H., Dietrich, R., Joachim, H., Praxis Dres Werner Erdle, Wilfried, D., Janna, D., Karl-Albrecht, R., Reinhold, V., Thomas, M., Peter, M., Uwe, H., Volker, E., Heinz, H., Heinz, L., Volker, L., Heiner, M., Christian, S., Herrmann, L., Thomas, B., Gunter, B., Susanne, K., Karsten, M., Sylvia, B., Muwafeg, A., Hans-Holger, E., Carsten, S., Peter, B., Laszlo, K., Britta, S., Wilhelm, H., Jens-Uwe, R., Andras Vertes Gabor Szantai, Andras, M., Nikosz, K., Zoltan, B., Erno, K., Balazs, G., Ferenc, J., Gizella, J., Sandor, K., Zoltan, L., Zsolt, M., Bela, M., Ebrahim, N., Tamas, H., Peter, P., Gabriella, S., Sandor, V., Andras, N., Gabriella, E., Judit, F., Mihaly, E., Giuliana Martini Leone Maria Cristina, Eros, T., Rita, S., Sophie, T., Giovanni Di Minno, Marco, M., Teresa Maria Caimi, Maria, T., Roberto, C., Daniela, P., Roberto, Q., Franco, C., Raffaele, F., Vincenzo, O., Raffaele, R., Roberto, S., Raimondo De Cristofaro, Giuliana, G., Angelo De Blasio, Jorge Salerno Uriate, Flavia, L., Enrico Maria Pogliani, Grzegorz, B., Michele, A., Antonio, M., Mauro, F., Arturo, R., Luciano, F., Andrea, M., Fabrizio, G., Luca, T., Maria, S., Sergio, N., Paolo, R., Antonio, A., Claudio, B., Filippo, T., Massimo, V., Maria, D., Maria Grazia Bongiorni, Silva, S., Alessandro, C., Corrado, L., Enrico, S., Gaetano, S., Tondo, C., Paolo, G., Carmine, M., Saverio, I., Hugo Ten Cate J, H.R., Andreas, L., Henk, A., Maarten, B., Mathijs, P., Coen van Guldener, Johannes, H., S H K P, R.N., Pieter, H., Walter, H., E Groenemeijer, B., Terpstra, W., Cees, B., L V, A.B., Eivind Berge Per Anton Sirnes, Erik, G., Torstein, H., Knut, E., Arne, H., Gunnar, S., Anders, Ø., Beraki, G., Arne, S., Peter, C., Torbjørn, Ø., Svein Høegh Henrichsen, Jan Erik Otterstad, Janina Stepinska Andrzej Gieroba, Malgorzata, B., Michal, O., Beata, W., Krystyna, L., Jaroslaw, Wieslaw, S., Jerzy, K., Roman, Z., Jaroslaw, H., Lucyna, S., Lech, K., Marcin, G., Piotr, M., Maciej, O., Grzegorz, K., Malgorzata, K., Zbigniew, L., Bozenna, O., Jerzy, L., Elzbieta, Z., Agnieszka, K., Malgorzata, C., Iwona, W., Grzegorz, O., Marek, B., Marcin, O., Grazyna, G., Piotr, R., Grzegorz, S., Ryszard, S., Boguslaw, O., Piotr, K., Krzysztof, G., Krzysztof, C., Jaroslaw, J., Pawel, M., Waldemar, M., Stanislaw, M., Roman, L., Jacek, B., Teresa, R., Grzegorz, R., Ewa, D., Jadwiga, N., Jozef, L., Vera Eltishcheva Roman Libis, Gadel, K., Dmitry, B., Liudmila, E., Alexander, K., Eduard, Y., Dmitry, Z., Olga, B., Olga, M., Evgeniy, M., Konstantin, Z., Tatyana, N., Yulia, M., Elena, P., Konstantin, S., Maria, R., Yulia, S., Alla, K., Konstantin, N., Oksana, Z., Anna, Z., Victor, K., Sergey, P., Maria, P., Anton, E., Elena Aleksandrova Oksana Drapkina, Alexander, V., Oleg, N., Petr, C., Svetlana, R., Mikhail, S., Borys, K., Alexey, U., Xavier Vinolas Pere Alvarez Garcia, Maria Fernanda Lopez Fernandez, Luis Tercedor Sanchez, Salvador Tranche Iparraguirre, Pere Toran Monserrat, Emilio Marquez Contreras, Jordi Isart Rafecas, Juan Motero Carrasco, Pablo Garcia Pavia, Casimiro Gomez Pajuelo, Luis Miguel Rincon Diaz, Luis Fernando Iglesias Alonso, Angel Grande Ruiz, Jordi Merce Klein, Jose Ramon Gonzalez Juanatey, Ines Monte Collado, Herminia Palacin Piquero, Carles Brotons Cuixart, Esther Fernandez Escobar, Joan Bayo, I.L., Cecilia Corros Vicente, Manuel Vida Gutierrez, Francisco Epelde Gonzalo, Carlos Alexandre Almeida Fernandez, Encarnacion Martinez Navarro, Juan Jose Montero Alia, Maria Barreda Gonzalez, Maria Angels Moleiro Oliva, Jose Iglesias Sanmartin, Mercedes Jimenez Gonzalez, Maria Del Mar Rodriguez Alvarez, Juan Herreros Melenchon, Tomas Ripoll Vera, Manuel Jimenez Navarro, Maria Vazquez Caamano, Maria Fe Arcocha Torres, Gonzalo Marcos Gomez, Andres Iniguez Romo, Miguel Angel Prieto Diaz, Mårten Rosenqvist Alexander Wirdby, Centrumkliniken, Jan, L., Kerstin, H., Micael, E., Arnor, E., Ulf, B., Liu, B., Anders, L., Lars-Bertil, O., Mikael, G., Lars, A., Lars, B., Claes, B., Ali, H., Björn, M., Marianne, E., Åke, O., Håkan, L., Peter, S., Katarina, T., Hans, H., Pyotr, P., Fredrik, B., Ingar, T., Milita, C., Jan-Erik, K., Agneta, A., Lennart, M., Johan, E., Jörgen, T., Aida, H., Steen, J., Per, S., Jan Steffel Johann Debrunner, Juerg, H.B., Dipen, S., Iurii Rudyk Vira Tseluyko, Oleksandr, K., Svitlana, Z., Igor, K., Oleksandr, P., Iryna, K., Nestor, S., Yuriy, M., Oleksiy, U., Olena, K., Yevgeniya, S., Oleg, S., Mykola, S., Andriy, Y., Susanna, T., Ivan, F., Will Murdoch Naresh Chauhan, Daryl, G., Louise, L., Ramila, P., Philip, S., Bennett, W., Alex, C., Niranjan, P., Jhittay, P., Andrew, R., S Kainth, M., Karim, L., Kevin, D., Gill, P., Joanna, M., Laura, H., Trevor, G., Helga, W., Cumberlidge, Colin, B., Catherine, B., Kevin, J., Shoeb, S., Richard, C., Bhupinder, S., Willcock, W., Sircar, S., John, C., Gilliand, A., Roman, B., Strieder, E., Peter, H., Anne, W., Michael, S., Graham, K., Bhaskhar, V., Nigel, B., Paul, E., Clark, M., John, B., Jennifer, L., Fisher, E., Tim, F., Richard, K., Neil, P., Elizabeth, A., Michael, A., Ramesh, C., Pete, W., Simon, F., Sue, F., Julian, T., Hasan, C., Gary, T., Dawn, T., Matt, P., Claire, S., Carolyn, P., Mark, R., Angus, J., Helen, S., Hywel, J., Claire, G., Matthew, B., Philip, W., Jehad, A., Simon, W., William, L., Phil, E., Frances, S., Neil, M., Stephen, R., Yvette, S., Richard, W., Philip, P., Paul, W., Preeti, P., Andrew, G., Railton, T., Emyr, D., Jonathan, M., Marc, J., Claire, H., Thompson, R., Bijoy, S., Keith, B., Susan, B., Helen, L., David, R., Ulka, C., Ikram, H., Paul, A., Claire, J., Phil, W., Jane, E., Lisa, G., Janet, G., Alison, M., Poland, K., Conor, M., Warke, A., Paul, C., Burns, D., Smith, R., Kamath, R., Jonathan, W., Ian, H., Stephen, V., Paul, R., Hilary, P., Jayesh, P., Amar, A., Nigel, H., Richard, D., Nigel, D., Catherine, N., Mark, D., Purnima, S., Sophia, G., Charlotte, H., Raife, O., Martin, A., Mira, P., Gordon, I., Shahid, A., Catherine, R., Fiaz, C., Sabrina, K., Stephanie, S., Sharon, P., Warwick, C., Neil, R., Amy Butler Steven Coates, Ben, W., Daniel, J., Steve, W., Diane, S., Toh, W., Mark, B., Melanie, D., David, C., Sarah, D., Ben, F., Nick, H., Henry, C., Jon, S., Tim, M., Salah, E., Diane, G., Justin, W., Richard, V., Karen, F., Rob, H., Kashif, Z., Catherine, L., Rebecca, W., Paul, M., Andre, B., Philip, C., Mike, W., Mark, P., Chaminda, D., Greg, R., James, B., Polly, J., Rajesh, M., Matthew, A., Robin, F., Nicolas, T., Simon, C., Rory, R., Simon, R., Christine, A., Ann, F., Andrew, H., Simon, D., Minnal, N., Iain, M., Jane, G., Phil, S., John, S., Emma, B., Adam Blenkhorn Bhuwanendu Singh, Penny, A., William van Gaal, Walter, A., Philip, T., Ron, L., Jens, K., Andrei, C., Hosen, K., David, E., John, F., Bronte, A., Thanh, P., James, R., David, O., Sang Cheol Bae, Harry, G., Patrick, C., Greg, S., Margaret, A., Maurits, B., Astin, L., John Eikelboom Robert Luton, Milan, G., Amritanshu Shekhar Pandey, Stephen, C., Rolland, L., Philippe, B., Félix, A., Joseph, B., John, H., Germain, P., Miranda du Preez, Bradley, S., Reginald, N., Ripple, D., Tomasz, H., Andrea, L., Ratika, P., James, C., Benoit, C., Brian, R., Jorge, B., Saul, V., Sameh, F., Ahmed Mowafy Azza Katta, Mazen, T., Moustafa, N., Mohamed, S., Seif Kamal Abou Seif, Tarek, K., Ahmed Abd El-Aziz, Nasser, T., Ashraf, R., Atef, E., Mohamed Gamal El Din, Magdi, E., Adel, E., David Kettles Junaid Bayat, Heidi, S., Adrian, H., Ynez, K., Riaz, G., Thayabran, P., Michele, G., Louis van Zyl, Hendrik, T., Andrew, M., Rikus, L., Deon, G., Pindile, M., Siddique, I., Fayzal, A., Johannes, E., Shambu, M., Wessel, O., Rehana, L., Veronica, U., Wael AlAl Mahmeed AbdullahNaeemi, Ghazi, Y., Nooshin, B., Munther, A., Rajan, M., Rupesh, S., Ahmed, N., Mohamed, I., Amrish, A., Mukesh, N., Ehab, M.E., Adel, W., Rajeev, G., Michael Cox Scott Beach, Peter, D., Stephen, F., Kevin, F., Miguel, F., W Michael Kutayli, Annette, Q., Niraj, S., Vance, W., Stephen, M., Mark, A., Edwin, B., Roddy, C., Ted, G., Rodney, I., Jorge, G., Howard, N., Pamela, R., Rajneesh, R., Marcus, W., Daniel, N., Keith, F., Ihsan, H., Robert, M., Sridevi, P., Daniel, T., Charles, T., Moustafa, M., Cas, C., Walter, P., Alisha, O., George, P., Jaspal, G., James, W., and Firas, K.

Subjects
Vitamin K antagonists, Atrial fibrillation, GARFIELD-AF, Non-vitamin K antagonist oral anticoagulants, Oral anticoagulation, Phenprocoumon, Settore MED/11 - Malattie dell'Apparato Cardiovascolare
Abstract

The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is a worldwide non-interventional study of stroke prevention in patients with non-valvular AF.52,080 patients with newly diagnosed AF were prospectively enrolled from 2010 to 2016. 4121 (7.9%) of these patients were recruited in DACH [Germany (n = 3567), Austria (n = 465) and Switzerland (n = 89) combined], and 47,959 patients were from 32 countries in other regions worldwide (ORW). Hypertension was most prevalent in DACH and ORW (85.3% and 75.6%, respectively). Diabetes, hypercholesterolaemia, carotid occlusive disease and vascular disease were more prevalent in DACH patients vs ORW (27.6%, 49.4%, 5.8% and 29.0% vs 21.7%, 40.9%, 2.8% and 24.5%). The use of non-vitamin K antagonist oral anticoagulants (NOACs) increased more in DACH over time. Management of vitamin K antagonists was suboptimal in DACH and ORW (time in therapeutic range of INR ≥ 65% in 44.6% and 44.4% of patients or ≥ 70% in 36.9% and 36.0% of patients, respectively). Adjusted rates of cardiovascular mortality and MI/ACS were higher in DACH while non-haemorrhagic stroke/systemic embolism was lower after 2-year follow-up.Similarities and dissimilarities in AF management and clinical outcomes are seen in DACH and ORW. The increased use of NOAC was associated with a mismatch of risk-adapted anticoagulation (over-and-undertreatment) in DACH. Suboptimal control of INR requires educational activities in both regional groups. Higher rates of cardiovascular death in DACH may reflect the higher risk profile of these patients and lower rates of non-haemorrhagic stroke could be associated with increased NOAC use.

Published
2022

10. Efficacy And Safety Of Aficamten In Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy: Interim Results From The Randomized Evaluation Of Dosing With Ck-3773274 In Hypertrophic Cardiomyopathy Open Label Extension Study

Author

Ahmad Masri, Theodore P. Abraham, Lubna Choudhury, Anjali T. Owens, Albree Tower-Rader, Florian Rader, Pablo Garcia-Pavia, Iacopo Olivotto, Caroline Coats, Michael A. Fifer, Scott D. Solomon, Hugh Watkins, Stephen B. Heitner, Daniel Jacoby, Stuart Kupfer, Fady I. Malik, Lisa Meng, Sharon L. Paige, Amy Wohltman, Martin S. Maron, and Sara Saberi

Subjects
Cardiology and Cardiovascular Medicine
Published
2023

12. LONG-TERM EFFICACY AND SAFETY OF AFICAMTEN IN PATIENTS WITH SYMPTOMATIC OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY

Author

Sara Saberi, Theodore P. Abraham, Lubna Choudhury, Anjali Tiku Owens, Albree Tower-Rader, Florian Rader, Pablo Garcia Pavia, Iacopo Olivotto, Caroline Coats, Michael A. Fifer, Scott D. Solomon, Hugh Watkins, Steve Heitner, Dan Jacoby, Stuart Kupfer, Fady I. Malik, Lisa Meng, Amy Wohltman, Martin S. Maron, and Ahmad Masri

Subjects
Cardiology and Cardiovascular Medicine
Published
2023

14. Role of Early Assesment of Diuresis and Natriuresis in Detecting In-Hospital Diuretic Resistance in Acute Heart Failure

Author

Belén García-Magallón, Marta Cobo-Marcos, Aitor Dávila Martiarena, Esther Montero Hernández, Maria Luisa Martín Jiménez, Aránzazu Martín García, Daniel De Castro Campos, Paula Vela Martín, Fernando Hernández Terciado, Ramón Garrido González, Andrea Matutano Muñoz, Daniel Escribano García, Fernando Domínguez, Ana Sainz Herrero, Camino Gómez Peñalba, Pablo Garcia-Pavia, and Javier Segovia

Subjects
Physiology, Physiology (medical)
Abstract

Background and Purpose: European Guidelines recommend early evaluation of diuresis and natriuresis after the first administration of diuretic to identify patients with insufficient diuretic response during acute heart failure. The aim of this work is to evaluate the prevalence and characteristics of patients with insufficient diuretic response according to this new algorithm.Methods: Prospective observational single centre study of consecutive patients with acute heart failure and congestive signs. Clinical evaluation, echocardiography and blood tests were performed. Diuretic naïve patients received 40 mg of intravenous furosemide. Patients on an oupatient diuretic regimen received 2 times the ambulatory dose. The diuresis volume was assessed 6 h after the first loop diuretic administration, and a spot urinary sample was taken after 2 h. Insufficient diuretic response was defined as natriuresis Results: From January 2020 to December 2021, 73 patients were included (59% males, median age 76 years). Of these, 21 patients (28.8%, 95%CI 18.4; 39.2) had an insufficient diuretic response. Diuresis volume was Conclusion: The diagnostic algorithm based on diuresis and natriuresis was able to detect up to 29% of patients with insufficient diuretic response, who showed some characteristics of more advanced disease.

Published
2022

15. Relationship Between Maximal Left Ventricular Wall Thickness and Sudden Cardiac Death in Childhood Onset Hypertrophic Cardiomyopathy

Author

Gabrielle Norrish, Tao Ding, Ella Field, Elena Cervi, Lidia Ziółkowska, Iacopo Olivotto, Diala Khraiche, Giuseppe Limongelli, Aris Anastasakis, Robert Weintraub, Elena Biagini, Luca Ragni, Terrence Prendiville, Sophie Duignan, Karen McLeod, Maria Ilina, Adrián Fernández, Chiara Marrone, Regina Bökenkamp, Anwar Baban, Peter Kubus, Piers E.F. Daubeney, Georgia Sarquella-Brugada, Sergi Cesar, Sabine Klaassen, Tiina H. Ojala, Vinay Bhole, Constancio Medrano, Orhan Uzun, Elspeth Brown, Ferran Gran, Gianfranco Sinagra, Francisco J. Castro, Graham Stuart, Gabriele Vignati, Hirokuni Yamazawa, Roberto Barriales-Villa, Luis Garcia-Guereta, Satish Adwani, Katie Linter, Tara Bharucha, Pablo Garcia-Pavia, Ana Siles, Torsten B. Rasmussen, Margherita Calcagnino, Caroline B. Jones, Hans De Wilde, Toru Kubo, Tiziana Felice, Anca Popoiu, Jens Mogensen, Sujeev Mathur, Fernando Centeno, Zdenka Reinhardt, Sylvie Schouvey, Costas O’Mahony, Rumana Z. Omar, Perry M. Elliott, Juan Pablo Kaski, Institut Català de la Salut, [Norrish G] Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London, United Kingdom. Institute of Cardiovascular Sciences, University College London, United Kingdom. [Ding T] Department of Statistical Science, University College London, United Kingdom. [Field E, Cervi E] Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London, United Kingdom. [Ziółkowska L] The Children’s Memorial Health Institute, Warsaw, Poland. [Olivotto I] Careggi University Hopsital, Florence, Italy. [Gran F] Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, University of Helsinki, Clinicum, Children's Hospital, HUS Children and Adolescents, Norrish, Gabrielle, Ding, Tao, Field, Ella, Cervi, Elena, Ziółkowska, Lidia, Olivotto, Iacopo, Khraiche, Diala, Limongelli, Giuseppe, Anastasakis, Ari, Weintraub, Robert, Biagini, Elena, Ragni, Luca, Prendiville, Terrence, Duignan, Sophie, Mcleod, Karen, Ilina, Maria, Fernandez, Adrian, Marrone, Chiara, Bökenkamp, Regina, Baban, Anwar, Kubus, Peter, Daubeney, Piers E F, Sarquella-Brugada, Georgia, Cesar, Sergi, Klaassen, Sabine, Ojala, Tiina H, Bhole, Vinay, Medrano, Constancio, Uzun, Orhan, Brown, Elspeth, Gran, Ferran, Sinagra, Gianfranco, Castro, Francisco J, Stuart, Graham, Vignati, Gabriele, Yamazawa, Hirokuni, Barriales-Villa, Roberto, Garcia-Guereta, Lui, Adwani, Satish, Linter, Katie, Bharucha, Tara, Garcia-Pavia, Pablo, Siles, Ana, Rasmussen, Torsten B, Calcagnino, Margherita, Jones, Caroline B, De Wilde, Han, Kubo, Toru, Felice, Tiziana, Popoiu, Anca, Mogensen, Jen, Mathur, Sujeev, Centeno, Fernando, Reinhardt, Zdenka, Schouvey, Sylvie, O'Mahony, Costa, Omar, Rumana Z, Elliott, Perry M, and Kaski, Juan Pablo

Subjects
Hypertrophy, Left Ventricular/complications, sistema cardiovascular::corazón::ventrículos cardíacos [ANATOMÍA], Heart Ventricles, FEATURES, enfermedades cardiovasculares::enfermedades cardíacas::paro cardíaco::muerte súbita cardíaca [ENFERMEDADES], Cardiomyopathy, Hypertrophic/complications, CHILDREN, Heart Ventricles/diagnostic imaging, DIAGNOSIS, Cor - Hipertròfia - Complicacions, Risk Assessment, LONG-TERM OUTCOMES, 3123 Gynaecology and paediatrics, Risk Factors, death, Physiology (medical), ADOLESCENTS, human, cardiovascular diseases, humans, death, sudden, Death, Sudden, Cardiac/epidemiology, Retrospective Studies, sudden, child, IDENTIFICATION, Mort sobtada, adult, Defibrillators, Implantable/adverse effects, Cardiovascular Diseases::Heart Diseases::Cardiomyopathies::Cardiomyopathy, Hypertrophic [DISEASES], Cardiomyopathy, Hypertrophic, Cardiovascular Diseases::Heart Diseases::Heart Arrest::Death, Sudden, Cardiac [DISEASES], hypertrophic cardiomyopathy, Defibrillators, Implantable, heart ventricle, enfermedades cardiovasculares::enfermedades cardíacas::miocardiopatías::miocardiopatía hipertrófica [ENFERMEDADES], Death, Sudden, Cardiac, Cardiovascular and Metabolic Diseases, 3121 General medicine, internal medicine and other clinical medicine, RISK-FACTORS, SURVIVAL, cardiovascular system, Hypertrophy, Left Ventricular, hypertrophy, Cardiology and Cardiovascular Medicine, TASK-FORCE, Cor - Ventricle esquerre, Cardiovascular System::Heart::Heart Ventricles [ANATOMY]
Abstract

Background: Maximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular hypertrophy has a nonlinear relationship with SCD, but it is not known whether the same complex relationship is seen in childhood. The aim of this study was to describe the relationship between left ventricular hypertrophy and SCD risk in a large international pediatric HCM cohort. Methods: The study cohort comprised 1075 children (mean age, 10.2 years [±4.4]) diagnosed with HCM (1–16 years) from the International Paediatric Hypertrophic Cardiomyopathy Consortium. Anonymized, noninvasive clinical data were collected from baseline evaluation and follow-up, and 5-year estimated SCD risk was calculated (HCM Risk-Kids). Results: MLVWT Z score was Z scores were associated with heart failure symptoms, unexplained syncope, left ventricular outflow tract obstruction, left atrial dilatation, and nonsustained ventricular tachycardia. One hundred twenty-two patients (71.3%) with MLVWT Z score ≥20 had coexisting risk factors for SCD. Over a median follow-up of 4.9 years (interquartile range, 2.3–9.3), 115 (10.7%) had an SCD event. Freedom from SCD event at 5 years for those with MLVWT Z scores Z score, peaking at Z score +23. The presence of coexisting risk factors had a summative effect on risk. Conclusions: In children with HCM, an inverted U-shaped relationship exists between left ventricular hypertrophy and estimated SCD risk. The presence of additional risk factors has a summative effect on risk. While MLVWT is important for risk stratification, it should not be used either as a binary variable or in isolation to guide implantable cardioverter defibrillator implantation decisions in children with HCM.

Published
2022

16. Temporal Trends of Wild-Type Transthyretin Amyloid Cardiomyopathy in the Transthyretin Amyloidosis Outcomes Survey

Author

Jose Nativi-Nicolau, Alfonso Siu, Angela Dispenzieri, Mathew S. Maurer, Claudio Rapezzi, Arnt V. Kristen, Pablo Garcia-Pavia, Samantha LoRusso, Márcia Waddington-Cruz, Olivier Lairez, Ronald Witteles, Doug Chapman, Leslie Amass, Martha Grogan, Fabio Adrian Barroso, Johan Van Cleemput, Nowell Fine, Hartmut Schmidt, Burkhard Gess, Henning Moelgaard, Violaine Planté-Bordeneuve, David Adams, Jocelyn Inamo, Giuseppe Vita, Calogero Lino Cirami, Marco Luigetti, Michele Emdin, Yoshiki Sekijima, Taro Yamashita, Eun-Seok Jeon, Maria Alejandra Gonzalez Duarte Briseno, Hans Nienhuis, Olga Azevedo, Josep Maria Campistol Plana, Juan Gonzalez Moreno, Jose Gonzalez Costello, Jonas Wixner, Yesim Parman, Sanjiv Shah, Dianna Quan, Tessa Marburger, Michael Polydefkis, Stephen Gottlieb, Jeffrey Ralph, Nitasha Sarswat, Jin Luo, Srinivas Murali, William Cotts, Brian Drachman, David Steidley, Scott Hummel, David Slosky, Hector Ventura, Daniel Jacoby, James Hoffman, James Tauras, Sasa Zivkovic, Jose Tallaj, Daniel Lenihan, and Christopher Mueller

Subjects
Pathology, medicine.medical_specialty, Registry, wild-type transthyretin amyloidosis, ATTR-CM, transthyretin amyloid cardiomyopathy, ATTRv amyloidosis, variant transthyretin amyloidosis, macromolecular substances, registry, NO, mental disorders, medicine, bone scintigraphy, NYHA, New York Heart Association, Original Research, TTR, transthyretin, biology, business.industry, Amyloidosis, ATTRwt amyloidosis, wild-type transthyretin amyloidosis, Wild type, nutritional and metabolic diseases, medicine.disease, Amyloid fibril, nervous system diseases, Transthyretin, Wild-type transthyretin amyloidosis, Oncology, ATTR amyloidosis, transthyretin amyloidosis, biology.protein, Cardiology and Cardiovascular Medicine, business, Amyloid cardiomyopathy, Bone scintigraphy, Q, quartile
Abstract

Background Transthyretin amyloid cardiomyopathy results from the accumulation of wild-type (ATTRwt) or variant (ATTRv) transthyretin amyloid fibrils in the myocardium. THAOS (Transthyretin Amyloidosis Outcomes Survey) is a global, longitudinal, observational survey of patients with ATTRv and ATTRwt amyloidosis and asymptomatic patients with transthyretin mutations. Objectives This study explored temporal trends in ATTRwt amyloidosis diagnoses using data from THAOS. Methods Using THAOS data from December 2007 to January 2020, the following comparisons were made according to year: ATTRwt amyloidosis diagnoses in the United States versus rest of the world, ATTRwt versus ATTRv amyloidosis with cardiac-associated mutations diagnoses, and ATTRwt amyloidosis diagnoses by tissue biopsy versus bone scintigraphy. Results There were 1,069 patients with ATTRwt amyloidosis and 525 with ATTRv amyloidosis with cardiac mutations enrolled in THAOS. The median time from symptom onset to ATTRwt amyloidosis diagnosis did not change over the past 5 years (>60 months from 2015–2019). ATTRwt amyloidosis diagnoses increased from 2 in 2005 to >100 per year from 2016, with a more pronounced increase in the United States compared with the rest of the world. Diagnoses of ATTRwt amyloidosis by tissue biopsy increased yearly and peaked in 2014 before declining, whereas diagnoses by bone scintigraphy increased markedly since 2011. ATTRv amyloidosis with cardiac mutation diagnoses increased from 3 in 2005 to 37 in 2011, then plateaued. The proportion of patients with ATTRwt amyloidosis diagnosed with New York Heart Association functional class III/IV heart failure decreased from 2012 (46.4%) to 2019 (16.0%). Conclusions In the past decade, ATTRwt amyloidosis diagnoses increased worldwide. Despite the growing utilization of bone scintigraphy, patients are diagnosed several years after symptom onset. (Transthyretin Amyloidosis Outcomes Survey [THAOS]; NCT00628745), Central Illustration

Published
2022

17. Abstract 10960: Genetic Overlap of Acute Myocarditis and Inherited Cardiomyopathy

Author

Amrit S Lota, Mark Hazebroek, Pantazis Theotokis, Rebecca Wassall, Sara Salmi, Brian Halliday, Upasana Tayal, Job Verdonschot, Devendra Meena, Antonio de Marvao, Alma Iacob, Daniel Hammersley, Richard Jones, Rick Wage, Rachel Buchan, Momina Yazdani, Michela Noseda, Tarun Mittal, Joyce Wong, Jan Lukas Robertus, John Baksi, Vassilios Vassiliou, Ioanna Tzoulaki, Antonios Pantazis, John Cleland, Paul J Barton, stuart cook, Dudley J Pennell, Pablo Garcia-Pavia, Leslie T Cooper, Stephane Heymans, James S Ware, and Sanjay K Prasad

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Background: Myocarditis may predispose to dilated cardiomyopathy (DCM) and sudden cardiac death (SCD). Familial data indicate a potential genetic susceptibility shared with arrhythmogenic cardiomyopathy (ACM). We present the first large-scale genotype-phenotype study of adults with acute myocarditis. Methods: A cohort comprising 336 consecutive patients with acute myocarditis was enrolled in London and Maastricht. All participants underwent targeted DNA sequencing for well-characterised cardiomyopathy-associated genes. The burden of rare protein altering variants (PAV) in ACM genes, DCM genes, and TTN specifically, were compared with local healthy controls sequenced on the same platform (n=1053). Case ascertainment was assessed against national hospital admission data. Results: We identified rare protein-altering variants in 23% of cases compared to 16% in controls (Δ+6.8%; p=0.021), with rare truncating variants (tv) in 6% of cases compared to Conclusion: We identified enrichment of cardiomyopathy gene variants in acute myocarditis patients, dominated by DSP-tv in those with normal LVEF and TTN-tv in those with reduced LVEF. Incorporation of genetic testing may be beneficial to identify such high-risk individuals and guide family screening in acute myocarditis patients.

Published
2021

18. Sex-Related Risk of Cardiac Involvement in Hereditary Transthyretin Amyloidosis: Insights From THAOS

Author

Angelo Giuseppe, Caponetti, Claudio, Rapezzi, Christian, Gagliardi, Agnese, Milandri, Angela, Dispenzieri, Arnt V, Kristen, Jonas, Wixner, Mathew S, Maurer, Pablo, Garcia-Pavia, Ivailo, Tournev, Violaine, Planté-Bordeneuve, Douglass, Chapman, Leslie, Amass, and Daniel, Lenihan

Subjects
Heart Failure, Male, Amyloid Neuropathies, Familial, Surveys and Questionnaires, Humans, Prealbumin, Female
Abstract

Because patients with ATTRv cardiomyopathy are more likely to be male, this analysis aimed to increase information on associations between sex and genotype, phenotype, and degree of myocardial involvement in ATTRv amyloidosis.Transthyretin amyloid cardiomyopathy is a progressive, fatal disease that occurs due to accumulation of wild-type or variant (ATTRv) transthyretin amyloid fibrils in the myocardium.The Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing global longitudinal observational survey of patients with ATTR amyloidosis and asymptomatic carriers with TTR mutations. Data from THAOS (data cutoff: January 6, 2020) were analyzed to determine any sex-based differences in genotype, phenotype, and presence of cardiac and neurological symptoms in patients with ATTRv amyloidosis and in patients with ATTRv amyloidosis and cardiomyopathy.There were 2,790 patients with ATTRv amyloidosis enrolled in THAOS, with male patients more likely to have symptoms of cardiac involvement and a cardiac phenotype. Male prevalence was greater in patients with more severe cardiac manifestations of disease, as assessed with N-terminal pro-B-type natriuretic peptide, left-ventricular (LV) ejection fraction, mean LV wall thickness divided by height, and LV mass index divided by height. Sex, age at disease onset, and genotype category were identified by multivariate analyses as risk factors for the development of cardiomyopathy (defined as increased LV septum thickness divided by height).In this analysis, myocardial involvement was more frequent and pronounced in male patients with ATTRv amyloidosis, suggesting that there may be biological characteristics that inhibit myocardial amyloid infiltration in females or facilitate it in males.

Published
2021

19. Clinical Profile of Cardiac Involvement in Danon Disease: A Multicenter European Registry

Author

Dor Lotan, Joel Salazar-Mendiguchía, Jens Mogensen, Faizan Rathore, Aris Anastasakis, Juan Kaski, Pablo Garcia-Pavia, Iacopo Olivotto, Philippe Charron, Elena Biagini, Anwar Baban, Giuseppe Limongelli, Waddah Ashram, Yishay Wasserstrum, Joseph Galvin, Esther Zorio, Attilio Iacovoni, Lorenzo Monserrat, Paolo Spirito, Maria Iascone, Michael Arad, Chana Mandel, Herminio Morillas, Esther Gonzalez-Lopez, Fernando Dominguez, Daniela Marchetti, Laura Pezzoli, Katie Anne Walsh, Catherine McGorrian, Raffaello Ditaranto, Giovanni Vitale, Eric Villard, Pascale Richard, Emanuele Monda, Martina Caiazza, Silvia Passantino, Francesca Girolami, Fabrizio Drago, Rachele Adorisio, Ella Field, Dov Freimark, Ulrik Baandrup, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CIC Pitié BT, Lotan, D., Salazar-Mendiguchia, J., Mogensen, J., Rathore, F., Anastasakis, A., Kaski, J., Garcia-Pavia, P., Olivotto, I., Charron, P., Biagini, E., Baban, A., Limongelli, G., Ashram, W., Wasserstrum, Y., Galvin, J., Zorio, E., Iacovoni, A., Monserrat, L., Spirito, P., Iascone, M., and Arad, M.

Subjects
Male, Pediatrics, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Cardiomyopathy, heart failure, Heart transplantation, 030204 cardiovascular system & hematology, Muscle hypertrophy, 0302 clinical medicine, Cause of Death, Danon disease, Registries, Child, 0303 health sciences, cardiomyopathie, Age Factors, General Medicine, Middle Aged, Glycogen Storage Disease Type IIb, 3. Good health, Europe, Treatment Outcome, Child, Preschool, Female, medicine.symptom, sex characteristics, hypertrophy, Arrhythmia, cardiomyopathies, Adult, medicine.medical_specialty, Adolescent, 03 medical and health sciences, Young Adult, metabolic, medicine, Humans, Myopathy, 030304 developmental biology, Aged, Heart Failure, business.industry, Myocardium, Infant, medicine.disease, Survival Analysis, Heart failure, business, Danon Disease
Abstract

Background: The X-linked Danon disease manifests by severe cardiomyopathy, myopathy, and neuropsychiatric problems. We designed this registry to generate a comprehensive picture of clinical presentations and outcome of patients with Danon disease in cardiomyopathy centers throughout Europe. Methods: Clinical and genetic data were collected in 16 cardiology centers from 8 European countries. Results: The cohort comprised 30 male and 27 female patients. The age at diagnosis was birth to 42 years in men and 2 to 65 in women. Cardiac involvement was observed in 96%. Extracardiac manifestations were prominent in men but not in women. Left ventricular (LV) hypertrophy was reported in 73% of male and 74% of female patients. LV systolic dysfunction was reported in 40% of men (who had LV ejection fraction, 34±11%) and 59% of women (LV ejection fraction, 28±13%). The risk of arrhythmia and heart failure was comparable among sexes. The age of first heart failure hospitalization was lower in men (18±6 versus 28±17 years; P Conclusions: Danon disease presents earlier in men than in women and runs a malignant course in both sexes, due to cardiac complications. Cardiomyopathy features, heart failure and arrhythmia, are similar among the sexes. Clinical diagnosis and management is extremely challenging in women due to phenotypic diversity and the absence of extracardiac manifestations.

Published
2020

21. Usefulness of natriuresis to predict in-hospital diuretic resistance

Author

Marta, Cobo-Marcos, Isabel, Zegri-Reiriz, Paloma, Remior-Perez, Sergio, Garcia-Gomez, Daniel, Garcia-Rodriguez, Fernando, Dominguez-Rodriguez, Aranzazu, Martin-Garcia, Pablo, Garcia-Pavia, and Javier, Segovia-Cubero

Subjects
Original Article
Abstract

Background: Urinary sodium excretion predicts long-term adverse events after discharge in patients with acute heart failure (AHF). The role of natriuresis as an early marker of poor diuretic response during an AHF episode has been scarcely investigated. We sought to evaluate whether early natriuresis or its change during heart failure hospitalization is associated with the development of in-hospital diuretic resistance (DR). Methods: This was a prospective, observational single center study of consecutive patients with AHF. Urine electrolytes were estimated from a spot urine sample within the first 6 hours following the first diuretic dose and 48 hours after admission. In-hospital DR was defined as poor diuretic response based on diuretic efficiency metrics and persistent congestion despite an intensive diuretic protocol. Results: Between January and December 2018, 143 patients were admitted for AHF. Of these, 102 fulfilled the inclusion criteria (60% males, median age 77 years [interquartile range [IQR]: 69-83), and 20 patients (19.6%) met the definition of DR. Early natriuresis was lower in patients with DR than in non-resistant patients (46 mEq/L [IQR: 38.5-80.0] vs 97.5 mEq/L [IQR: 70.5-113.5], P

Published
2020

22. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Iacopo Olivotto, Artur Oreziak, Roberto Barriales-Villa, Theodore P Abraham, Ahmad Masri, Pablo Garcia-Pavia, Sara Saberi, Neal K Lakdawala, Matthew T Wheeler, Anjali Owens, Milos Kubanek, Wojciech Wojakowski, Morten K Jensen, Juan Gimeno-Blanes, Kia Afshar, Jonathan Myers, Sheila M Hegde, Scott D Solomon, Amy J Sehnert, David Zhang, Wanying Li, Mondira Bhattacharya, Jay M Edelberg, Cynthia Burstein Waldman, Steven J Lester, Andrew Wang, Carolyn Y Ho, Daniel Jacoby, Jozef Bartunek, Antoine Bondue, Emeline Van Craenenbroeck, David Zemanek, Morten Jensen, Jens Mogensen, Jens Jakob Thune, Philippe Charron, Albert Hagege, Olivier Lairez, Jean-Noël Trochu, Christoph Axthelm, Hans-Dirk Duengen, Norbert Frey, Veselin Mitrovic, Michael Preusch, Jeanette Schulz-Menger, Tim Seidler, Michael Arad, Majdi Halabi, Amos Katz, Daniel Monakier, Offir Paz, Samuel Viskin, Donna Zwas, Hans Peter Brunner-La Rocca, Michelle Michels, Dariusz Dudek, Zofia Oko-Sarnowska, Nuno Cardim, Helder Pereira, Pablo García Pavia, Juan Gimeno Blanes, Rafael Hidalgo Urbano, Luis Miguel Rincón Diaz, Perry Elliott, Zaheer Yousef, Theodore Abraham, Paulino Alvarez, Richard Bach, Richard Becker, Lubna Choudhury, David Fermin, John Jefferies, Christopher Kramer, Neal Lakdawala, Steven Lester, Ali Marian, Mathew Maurer, Sherif Nagueh, David Owens, Florian Rader, Mark Sherrid, Jamshid Shirani, John Symanski, Aslan Turer, Omar Wever-Pinzon, Matthew Wheeler, Timothy Wong, Mohamad Yamani, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), RS: Carim - H02 Cardiomyopathy, MUMC+: MA Med Staf Spec Cardiologie (9), and Cardiologie

Subjects
medicine.medical_specialty, hypertrophic cardiomyopathy, mavacamten, LVOTO, [SDV]Life Sciences [q-bio], Cardiomyopathy, EXERCISE, 030204 cardiovascular system & hematology, Placebo, DIAGNOSIS, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Clinical endpoint, MANAGEMENT, Medicine, Ventricular outflow tract, 030212 general & internal medicine, OUTCOMES, business.industry, NATRIURETIC PEPTIDE, Hypertrophic cardiomyopathy, General Medicine, medicine.disease, Pathophysiology, 3. Good health, Clinical trial, Cardiology, business, TASK-FORCE
Abstract

Background: Cardiac muscle hypercontractility is a key pathophysiological abnormality in hypertrophic cardiomyopathy, and a major determinant of dynamic left ventricular outflow tract (LVOT) obstruction. Available pharmacological options for hypertrophic cardiomyopathy are inadequate or poorly tolerated and are not disease-specific. We aimed to assess the efficacy and safety of mavacamten, a first-in-class cardiac myosin inhibitor, in symptomatic obstructive hypertrophic cardiomyopathy. Methods: In this phase 3, randomised, double-blind, placebo-controlled trial (EXPLORER-HCM) in 68 clinical cardiovascular centres in 13 countries, patients with hypertrophic cardiomyopathy with an LVOT gradient of 50 mm Hg or greater and New York Heart Association (NYHA) class II–III symptoms were assigned (1:1) to receive mavacamten (starting at 5 mg) or placebo for 30 weeks. Visits for assessment of patient status occurred every 2–4 weeks. Serial evaluations included echocardiogram, electrocardiogram, and blood collection for laboratory tests and mavacamten plasma concentration. The primary endpoint was a 1·5 mL/kg per min or greater increase in peak oxygen consumption (pVO2) and at least one NYHA class reduction or a 3·0 mL/kg per min or greater pVO2 increase without NYHA class worsening. Secondary endpoints assessed changes in post-exercise LVOT gradient, pVO2, NYHA class, Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS), and Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness-of-Breath subscore (HCMSQ-SoB). This study is registered with ClinicalTrials.gov, NCT03470545. Findings: Between May 30, 2018, and July 12, 2019, 429 adults were assessed for eligibility, of whom 251 (59%) were enrolled and randomly assigned to mavacamten (n=123 [49%]) or placebo (n=128 [51%]). 45 (37%) of 123 patients on mavacamten versus 22 (17%) of 128 on placebo met the primary endpoint (difference +19·4%, 95% CI 8·7 to 30·1; p=0·0005). Patients on mavacamten had greater reductions than those on placebo in post-exercise LVOT gradient (−36 mm Hg, 95% CI −43·2 to −28·1; p2 (+1·4 mL/kg per min, 0·6 to 2·1; p=0·0006), and improved symptom scores (KCCQ-CSS +9·1, 5·5 to 12·7; HCMSQ-SoB −1·8, −2·4 to −1·2; p

Published
2020

23. Left ventricular non-compaction: genetics and embryology

Author

Pablo Garcia-Pavia and Fernando Dominguez

Abstract

Left ventricular non-compaction (LVNC) is a rare disorder that is considered an ‘unclassified cardiomyopathy’ by the European Society of Cardiology. Several different gene mutations related to LVNC have been identified, involving sarcomeric, cytoskeletal, Z-line, ion channel, mitochondrial, and signalling proteins. However, there is broad genetic overlap between LVNC and other inherited cardiac diseases such as dilated cardiomyopathy and hypertrophic cardiomyopathy. LVNC could also be part of multisystemic genetic entities such as Barth syndrome, or accompany congenital heart defects.

Published
2018

24. Gene network and familial analyses uncover a gene network involving Tbx5/Osr1/Pcsk6 interaction in the second heart field for atrial septation

Author

Xiaohua Zhang, Nathan Curry, Lun Zhou, Qin Wang, Linglin Xie, Pablo Garcia-Pavia, Ke Zhang, Damian Heine Suñer, Jielin Liu, and Menglan Xiang

Subjects
Heart Defects, Congenital, 0301 basic medicine, Cellular differentiation, Mutant, Gene regulatory network, Mice, Transgenic, Protein Serine-Threonine Kinases, Biology, Heart Septal Defects, Atrial, Atrial septal defects, Transcriptome, Mice, 03 medical and health sciences, 0302 clinical medicine, Gene expression, Genetics, Animals, Humans, Gene Regulatory Networks, KEGG, Molecular Biology, Gene, Genetics (clinical), Serine Endopeptidases, Articles, General Medicine, Pedigree, HEK293 Cells, 030104 developmental biology, Proprotein Convertases, T-Box Domain Proteins, 030217 neurology & neurosurgery, Signal Transduction
Abstract

Atrial septal defects (ASDs) are a common human congenital heart disease (CHD) that can be induced by genetic abnormalities. Our previous studies have demonstrated a genetic interaction between Tbx5 and Osr1 in the second heart field (SHF) for atrial septation. We hypothesized that Osr1 and Tbx5 share a common signaling networking and downstream targets for atrial septation. To identify this molecular networks, we acquired the RNA-Seq transcriptome data from the posterior SHF of wild-type, Tbx5(+/) (-), Osr1(+/-), Osr1(-/-) and Tbx5(+/-)/Osr1(+/-) mutant embryos. Gene set analysis was used to identify the Kyoto Encyclopedia of Genes and Genomes pathways that were affected by the doses of Tbx5 and Osr1. A gene network module involving Tbx5 and Osr1 was identified using a non-parametric distance metric, distance correlation. A subset of 10 core genes and gene-gene interactions in the network module were validated by gene expression alterations in posterior second heart field (pSHF) of Tbx5 and Osr1 transgenic mouse embryos, a time-course gene expression change during P19CL6 cell differentiation. Pcsk6 was one of the network module genes that were linked to Tbx5. We validated the direct regulation of Tbx5 on Pcsk6 using immunohistochemical staining of pSHF, ChIP-quantitative polymerase chain reaction and luciferase reporter assay. Importantly, we identified Pcsk6 as a novel gene associated with ASD via a human genotyping study of an ASD family. In summary, our study implicated a gene network involving Tbx5, Osr1 and Pcsk6 interaction in SHF for atrial septation, providing a molecular framework for understanding the role of Tbx5 in CHD ontogeny.

Published
2016

25. Successful treatment of healthcare-associated

Author

Isabel, Zegri-Reiriz, Marta, Cobo-Marcos, Begoña, Rodriguez-Alfonso, Rosario, Millán, Fernando, Dominguez, Alberto, Forteza, Pablo, Garcia-Pavia, and Antonio, Ramos-Martinez

Subjects
18Fluorodeoxyglucose positron emission tomography combined with computed tomography, Interferon-gamma 1b, Grand Rounds, Case report, Mycobacterium chimaera, Infective endocarditis, Aortic valve surgery
Abstract

Background Since 2011, several cases of health care-related disseminated Mycobacterium chimaera infection outbreaks have been reported subsequent to cardiac surgery. Diagnosis is difficult and the prognosis is extremely poor despite long-term antibiotic treatment and surgery. Case summary We report a Spanish case of M. chimaera infective endocarditis (IE) with disseminated infection. The patient was treated with long-term antibiotic therapy, valve replacement, and the novel use of interferon-gamma as adjuvant therapy. In addition, [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) was used in combination with computed tomography (CT) to facilitate the diagnosis as well as to determine the duration of antibiotics and success of treatment. Discussion Diagnosing M. chimaera IE is difficult and requires a high index of clinical suspicion. Controlling the infection is even more difficult. Interferon-g used adjuvant to surgery and antibiotic therapy could be useful in achieving this goal. Given that the appropriate duration of antibiotics is unknown, FDG PET/CT could also be a valuable tool for determining when antibiotic therapy can be withdrawn.

Published
2018

26. Infective Endocarditis in Patients With Bicuspid Aortic Valve or Mitral Valve Prolapse

Author

Isabel Zegri-Reiriz, Arístides de Alarcón, Patricia Muñoz, Manuel Martínez Sellés, Victor González-Ramallo, Jose M. Miro, Carles Falces, Claudia Gonzalez Rico, Xabier Kortajarena Urkola, José Antonio Lepe, Regino Rodriguez Alvarez, Jose Maria Reguera Iglesias, Enrique Navas, Fernando Dominguez, Pablo Garcia-Pavia, Fernando Fernández Sánchez, Mariam Noureddine, Gabriel Rosas, Javier de la Torre Lima, José Aramendi, Elena Bereciartua, María José Blanco, Roberto Blanco, María Victoria Boado, Marta Campaña Lázaro, Alejandro Crespo, Josune Goikoetxea, José Ramón Iruretagoyena, Josu Irurzun Zuazabal, Leire López-Soria, Miguel Montejo, Javier Nieto, David Rodrigo, David Rodríguez, Regino Rodríguez, Yolanda Vitoria, Roberto Voces, María Victoria García López, Radka Ivanova Georgieva, Guillermo Ojeda, Isabel Rodríguez Bailón, Josefa Ruiz Morales, Ana María Cuende, Tomás Echeverría, Ana Fuerte, Eduardo Gaminde, Miguel Ángel Goenaga, Pedro Idígoras, José Antonio Iribarren, Alberto Izaguirre Yarza, Carlos Reviejo, Rafael Carrasco, Vicente Climent, Patricio Llamas, Esperanza Merino, Joaquín Plazas, Sergio Reus, Nemesio Álvarez, José María Bravo-Ferrer, Laura Castelo, José Cuenca, Pedro Llinares, Enrique Miguez Rey, María Rodríguez Mayo, Efrén Sánchez, Dolores Sousa Regueiro, Francisco Javier Martínez, María del Mar Alonso, Beatriz Castro, Dácil García Rosado, Mª del Carmen Durán, Mª Antonia Miguel Gómez, Juan Lacalzada, Ibrahim Nassar, Antonio Plata Ciezar, José Mª Reguera Iglesias, Víctor Asensi Álvarez, Carlos Costas, Jesús de la Hera, Jonnathan Fernández Suárez, Lisardo Iglesias Fraile, Víctor León Arguero, José López Menéndez, Pilar Mencia Bajo, Carlos Morales, Alfonso Moreno Torrico, Carmen Palomo, Begoña Paya Martínez, Ángeles Rodríguez Esteban, Raquel Rodríguez García, Mauricio Telenti Asensio, Manuel Almela, Juan Ambrosioni, Manuel Azqueta, Mercè Brunet, Marta Bodro, Ramón Cartañá, Carlos Falces, Guillermina Fita, David Fuster, Cristina García de la Mària, Marta Hernández-Meneses, Jaume Llopis Pérez, Francesc Marco, José María Miró, Asunción Moreno, David Nicolás, Salvador Ninot, Eduardo Quintana, Carlos Paré, Daniel Pereda, Juan Manuel Pericás, José Luis Pomar, José Ramírez, Irene Rovira, Elena Sandoval, Marta Sitges, Dolors Soy, Adrián Téllez, José M. Tolosana, Bárbara Vidal, Jordi Vila, Iván Adán, Javier Bermejo, Emilio Bouza, Daniel Celemín, Gregorio Cuerpo Caballero, Antonia Delgado Montero, Ana Fernández Cruz, Ana García Mansilla, María Eugenia García Leoni, Víctor González Ramallo, Martha Kestler Hernández, Amaia Mari Hualde, Mercedes Marín, Manuel Martínez-Sellés, María Cruz Menárguez, Cristina Rincón, Hugo Rodríguez-Abella, Marta Rodríguez-Créixems, Blanca Pinilla, Ángel Pinto, Maricela Valerio, Pilar Vázquez, Eduardo Verde Moreno, Isabel Antorrena, Belén Loeches, Alejandro Martín Quirós, Mar Moreno, Ulises Ramírez, Verónica Rial Bastón, María Romero, Araceli Saldaña, Jesús Agüero Balbín, Carlos Armiñanzas Castillo, Ana Arnaiz, Francisco Arnaiz de las Revillas, Manuel Cobo Belaustegui, María Carmen Fariñas, Concepción Fariñas-Álvarez, Rubén Gómez Izquierdo, Iván García, Claudia González Rico, Manuel Gutiérrez-Cuadra, José Gutiérrez Díez, Marcos Pajarón, José Antonio Parra, Ramón Teira, Jesús Zarauza, Fernando Domínguez, Pablo García-Pavía, Jesús González Mirelis, Beatriz Orden, Antonio Ramos, Marta Cobo-Marcos, Tomasa Centella, José Manuel Hermida, José Luis Moya, Pilar Martín-Dávila, Enrique Oliva, Alejandro del Río, Soledad Ruiz, Carmen Hidalgo Tenorio, Manuel Almendro Delia, Omar Araji, José Miguel Barquero, Román Calvo Jambrina, Marina de Cueto, Juan Gálvez Acebal, Irene Méndez, Isabel Morales, Luis Eduardo López-Cortés, Emilio García, Juan Luis Haro, Francisco López, Rafael Luque, Luis Javier Alonso, Pedro Azcárate, José Manuel Azcona Gutiérrez, José Ramón Blanco, Lara García-Álvarez, José Antonio Oteo, Mercedes Sanz, Natividad de Benito, Mercé Gurguí, Cristina Pacho, Roser Pericas, Guillem Pons, Ángel Luis Fernández, Amparo Martínez, Arturo Prieto, Benito Regueiro, Marino Vega, Andrés Canut Blasco, José Cordo Mollar, Juan Carlos Gainzarain Arana, Oscar García Uriarte, Alejandro Martín López, Zuriñe Ortiz de Zárate, José Antonio Urturi Matos, Gloria García Domínguez, Antonio Sánchez-Porto, José Mª Arribas Leal, Elisa García Vázquez, Alicia Hernández Torres, Ana Blázquez, Gonzalo de la Morena Valenzuela, Ángel Alonso, Javier Aramburu, Felicitas Elena Calvo, Anai Moreno Rodríguez, Paola Tarabini-Castellani, Eva Heredero Gálvez, Carolina Maicas Bellido, José Largo Pau, María Antonia Sepúlveda, Pilar Toledano Sierra, Sadaf Zafar Iqbal-Mirza, Eva Cascales Alcolea, Pilar Egea Serrano, José Joaquín Hernández Roca, Ivan Keituqwa Yañez, Ana Peláez Ballesta, Víctor Soriano, Eduardo Moreno Escobar, Alejandro Peña Monje, Valme Sánchez Cabrera, David Vinuesa García, María Arrizabalaga Asenjo, Carmen Cifuentes Luna, Juana Núñez Morcillo, Mª Cruz Pérez Seco, Aroa Villoslada Gelabert, Carmen Aured Guallar, Nuria Fernández Abad, Pilar García Mangas, Marta Matamala Adell, Mª Pilar Palacián Ruiz, Juan Carlos Porres, Begoña Alcaraz Vidal, Nazaret Cobos Trigueros, María Jesús Del Amor Espín, José Antonio Giner Caro, Roberto Jiménez Sánchez, Amaya Jimeno Almazán, Alejandro Ortín Freire, Monserrat Viqueira González, Pere Pericás Ramis, Mª Ángels Ribas Blanco, Enrique Ruiz de Gopegui Bordes, Laura Vidal Bonet, Mª Carmen Bellón Munera, Elena Escribano Garaizabal, Antonia Tercero Martínez, and Juan Carlos Segura Luque

Subjects
Adult, Male, medicine.medical_specialty, bicuspid aortic valve, Enfermedad cardiovascular, Heart Valve Diseases, 030204 cardiovascular system & hematology, Intracardiac injection, 03 medical and health sciences, Tratamiento médico, 0302 clinical medicine, Bicuspid aortic valve, Bicuspid Aortic Valve Disease, medicine, Mitral valve prolapse, Endocarditis, Humans, In patient, 030212 general & internal medicine, Registries, Antibiotic prophylaxis, Antibióticos, Aged, Endocarditis infecciosa, Mitral Valve Prolapse, antibiotic prophylaxis, business.industry, Incidence (epidemiology), Antibiotic Prophylaxis, Middle Aged, medicine.disease, Surgery, Infective endocarditis, Aortic Valve, Válvulas cardíacas, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Background: There is little information concerning infective endocarditis (IE) in patients with bicuspid aortic valve (BAV) or mitral valve prolapse (MVP). Currently, IE antibiotic prophylaxis (IEAP) is not recommended for these conditions. Objectives: This study sought to describe the clinical and microbiological features of IE in patients with BAV and MVP and compare them with those of IE patients with and without IEAP indication, to determine the potential benefit of IEAP in these conditions. Methods: This analysis involved 3,208 consecutive IE patients prospectively included in the GAMES (Grupo de Apoyo al Manejo de la Endocarditis infecciosa en España) registry at 31 Spanish hospitals. Patients were classified as high-risk IE with IEAP indication (high-risk group; n = 1,226), low- and moderate-risk IE without IEAP indication (low/moderate-risk group; n = 1,839), and IE with BAV (n = 54) or MVP (n = 89). Results: BAV and MVP patients had a higher incidence of viridans group streptococci IE than did high-risk group and low/moderate-risk group patients (35.2% and 39.3% vs. 12.1% and 15.0%, respectively; all p < 0.01). A similar pattern was seen for IE from suspected odontologic origin (14.8% and 18.0% vs. 5.8% and 6.0%; all p < 0.01). BAV and MVP patients had more intracardiac complications than did low/moderate-risk group (50% and 47.2% vs. 30.6%, both p < 0.01) patients and were similar to high-risk group patients. Conclusions: IE in patients with BAV and MVP have higher rates of viridans group streptococci IE and IE from suspected odontologic origin than in other IE patients, with a clinical profile similar to that of high-risk IE patients. Our findings suggest that BAV and MVP should be classified as high-risk IE conditions and the case for IEAP should be reconsidered. Sin financiación 18.639 JCR (2018) Q1, 3/136 Cardiac & Cardiovascular Systems 9.280 SJR (2018) Q1, 1/365 Cardiology and Cardiovascular Medicine No data IDR 2018 UEM

Published
2018

27. Dilated cardiomyopathy due to BLC2-associated athanogene 3 (BAG3) mutations

Author

Fernando Domínguez, Sofía Cuenca, Zofia Bilińska, Rocío Toro, Eric Villard, Roberto Barriales-Villa, Juan Pablo Ochoa, Folkert Asselbergs, Arjan Sammani, Maria Franaszczyk, Mohammed Akhtar, Maria José Coronado-Albi, Diego Rangel-Sousa, Jose F. Rodriguez-Palomares, Juan Jiménez-Jáimez, José Manuel Garcia-Pinilla, Tomás Ripoll-Vera, Maria Victoria Mogollón-Jiménez, Ana Fontalba-Romero, Dolores Garcia-Medina, Julian Palomino-Doza, David de Gonzalo-Calvo, Marcos Cicerchia, Joel Salazar-Mendiguchia, Clara Salas, Sabine Pankuweit, Thomas Morris Hey, Jens Mogensen, Paul J. Barton, Philippe Charron, Perry Elliott, Pablo Garcia-Pavia, Hans Eiskjær, Roberto Barriales, Xusto Fernández Fernández, Lorenzo Monserrat, Maria Victoria Mogollón, Tomás Ripoll, Pascale Richard, Julian Palomino Doza, Ana Fontalba, Luis Alonso-Pulpón, Marta Cobo-Marcos, Manuel Gómez-Bueno, Esther González-López, Aitor Hernández-Hernández, Francisco José Hernández-Pérez, Ángela López-Sainz, Alejandra Restrepo-Córdoba, Javier Segovia-Cubero, Rocio Toro, Félix Rosa Longobardo, Javier Limeres, Jose Manuel Garcia-Pinilla, Miguel A. López-Garrido, Juan Jiménez-Jaimez, Diego Rangel Sousa, Maria Luisa Peña, Thomas Morris-Hey, Stuart A. Cook, William Midwinter, Angharad M. Roberts, James S. Ware, Roddy Walsh, Perry M. Elliott, Luis Rocha-Lopes, Konstantinos Savvatis, Petros Syrris, Ewa Michalak, Rafal Ploski, Malgorzata Sobieszczanska-Malek, Annette Baas, Dennis Dooijes, Instituto de Salud Carlos III, Fundación Progreso y Salud, Ministerio de Economía y Competitividad (España), Mutual Médica, European Research Area Network on Cardiovascular Diseases, British Heart Foundation, Wellcome Trust, National Institute for Health Research (UK), Danish Heart Foundation, University of Southern Denmark, Odense University Hospital, Competence Network for Heart Failure (Germany), Dutch Heart Foundation, European Commission, Health In Code, Department of Health, and Cardiology

Subjects
0301 basic medicine, Male, medicine.medical_treatment, Cardiomyopathy, 030204 cardiovascular system & hematology, Cohort Studies, Electrocardiography, 0302 clinical medicine, Interquartile range, genetics, Heart transplantation, BAG3, Incidence (epidemiology), Dilated cardiomyopathy, Middle Aged, 1117 Public Health And Health Services, Cohort, Cardiology, cardiovascular system, Female, Cardiology and Cardiovascular Medicine, Adult, Cardiomyopathy, Dilated, medicine.medical_specialty, Adolescent, 1102 Cardiovascular Medicine And Haematology, Article, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Journal Article, Humans, Animals, cardiovascular diseases, Adaptor Proteins, Signal Transducing, Heart Failure, business.industry, medicine.disease, dilated cardiomyopathy, 030104 developmental biology, Cardiovascular System & Hematology, Ventricular assist device, Heart failure, Mutation, Cats, prognosis, business, Apoptosis Regulatory Proteins, Follow-Up Studies
Abstract

[Background] The BAG3 (BLC2-associated athanogene 3) gene codes for an antiapoptotic protein located on the sarcomere Z-disc. Mutations in BAG3 are associated with dilated cardiomyopathy (DCM), but only a small number of cases have been reported to date, and the natural history of BAG3 cardiomyopathy is poorly understood. [Objectives] This study sought to describe the phenotype and prognosis of BAG3 mutations in a large multicenter DCM cohort. [Methods] The study cohort comprised 129 individuals with a BAG3 mutation (62% males, 35.1 ± 15.0 years of age) followed at 18 European centers. Localization of BAG3 in cardiac tissue was analyzed in patients with truncating BAG3 mutations using immunohistochemistry. [Results] At first evaluation, 57.4% of patients had DCM. After a median follow-up of 38 months (interquartile range: 7 to 95 months), 68.4% of patients had DCM and 26.1% who were initially phenotype-negative developed DCM. Disease penetrance in individuals >40 years of age was 80% at last evaluation, and there was a trend towards an earlier onset of DCM in men (age 34.6 ± 13.2 years vs. 40.7 ± 12.2 years; p = 0.053). The incidence of adverse cardiac events (death, left ventricular assist device, heart transplantation, and sustained ventricular arrhythmia) was 5.1% per year among individuals with DCM. Male sex, decreased left ventricular ejection fraction. and increased left ventricular end-diastolic diameter were associated with adverse cardiac events. Myocardial tissue from patients with a BAG3 mutation showed myofibril disarray and a relocation of BAG3 protein in the sarcomeric Z-disc. [Conclusions] DCM caused by mutations in BAG3 is characterized by high penetrance in carriers >40 years of age and a high risk of progressive heart failure. Male sex, decreased left ventricular ejection fraction, and enlarged left ventricular end-diastolic diameter are associated with adverse outcomes in patients with BAG3 mutations., This work was supported by grants from the following institutions: Instituto de Salud Carlos III (ISCIII) (PI14/ 0967, PI15/01551, AC16/0014), CIBERCV (CB16/11/00403), Progreso and Salud Foundation (Junta de Andalucia) (PI-0011/201), Ministry of Economy, Industry and Competitiveness (IJCI-2016-29393), Mutual Medical (Research Award 2017), ERA-CVD Joint Transnational Call 2016 (Genprovic), British Heart Foundation (SP/10/10/28431), Wellcome Trust (107469/Z/15/), NIHR Royal Brompton Cardiovascular Biomedical Research Unit, NIHR Imperial Biomedical Research Center, Health Innovation Challenge Fund award from the Wellcome Trust and Department of Health, U.K. (HICF-R6-373), Danish Heart Foundation (16-R107-A6617), University of Southern Denmark, the Region of Southern Denmark, Odense University Hospital, German Competence Network Heart Failure, (TP9, FKZ 01GI0205), DETECTIN-HF project (ERA-CVD framework), and PROMEX Charitable Foundation. UCL Hospitals NIHR Biomedical Research Center and Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON2015-12 eDETECT and CVON2014-40 DOSIS. The CNIC is supported by the Ministry of Economy, Industry and Competitiveness and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Grants from ISCIII and the Spanish Ministry of Economy and Competitiveness are supported by the Plan Estatal de IþDþI 2013-2016 – European Regional Development Fund (FEDER) “A way of making Europe.” The Hospital Universitario Puerta de Hierro Majadahonda, Hôpital PitiéSalpêtrière, and Saint Bartholomews’ Hospital are members of the European Reference Network for rare, low-prevalence, and complex diseases of the heart (ERN GUARD-Heart). Drs. Ochoa, Cicerchia, and Salazar-Mendiguchia are employees of Health In Code.

Published
2018

28. Mitochondrial Cardiomyopathies Associated With the m.3243A>G Mutation in the MT-TL1 Gene: Two Sides of the Same Coin

Author

Belén Bornstein, Luis Alonso-Pulpón, Pablo Garcia-Pavia, Marta Cobo-Marcos, Aurelio Hernández-Laín, and María Gallego-Delgado

Subjects
medicine.diagnostic_test, business.industry, General Medicine, Mitochondrion, Molecular biology, MT-TL1, chemistry.chemical_compound, chemistry, DNA Mutational Analysis, Mutation (genetic algorithm), Biopsy, Medicine, M 3243a g, business, Gene, DNA
Published
2015

30. A NEW TOOL FOR MYOCARDIAL FIBROSIS DETECTION IN HYPERTROPHIC CARDIOMYOPATHY: A DOUBLE PEAK OF STRAIN RATE BY SPECKLE TRACKING AND CORRELATION WITH MAGNETIC RESONANCE IMAGING

Author

DanielaCristina Mitroi, Jesus G Mirelis, Vanessa Moñivas Palomero, Susana Mingo Santos, Luis Alonso Pulpon, Ines Garcia Lunar, Miguel Angel Cavero Gibanel, and Pablo Garcia Pavia

Subjects
medicine.medical_specialty, medicine.diagnostic_test, business.industry, Hypertrophic cardiomyopathy, Magnetic resonance imaging, Strain rate, medicine.disease, Tracking (particle physics), Speckle pattern, Internal medicine, medicine, Cardiology, Myocardial fibrosis, Cardiology and Cardiovascular Medicine, business
Published
2011

Catalog

Books, media, physical & digital resources
See catalog results