Concomitant Aficamten and Disopyramide in Symptomatic Obstructive Hypertrophic Cardiomyopathy
| Title: | Concomitant Aficamten and Disopyramide in Symptomatic Obstructive Hypertrophic Cardiomyopathy |
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| Authors: | Masri, A; Maron, MS; Abraham, TP; Nassif, ME; Barriales-Villa, R; Bilen, O; Coats, CJ; Elliott, P; Garcia-Pavia, P; Massera, D; Olivotto, I; Oreziak, A; Owens, AT; Saberi, S; Solomon, SD; Tower-Rader, A; Heitner, SB; Jacoby, DL; Melloni, C; Wei, J; Sherrid, MV; Michels, M; Choudhury, L; Kramer, C; Lakdawala, NK; Nagueh, SF; Rader, F; Symanski, JD; Turer, A; Wang, A; Wong, T; Zhang, Y; Yang, H; Shao, C; Yuan, Z; Zeng, Q; Li, X; Ma, C; Wang, Y; Shu, Y; Chen, M; Tao, L; Wang, J; Yu, Z; Cheng, X; Hong, K; Zemanek, D; Bundgaard, H; Thune, J; Jensen, M; Mogensen, J; Hagège, A; Habib, G; Charron, P; Lhermusier, T; Trochu, J-N; Reant, P; Logeart, D; Mitrovic, V; Bekfani, T; Edelman, F; Seidler, T; Meder, B; Schulze, PC; Stoerk, S; Rassaf, T; Merkely, B; Zfat-Zwas, D; Arad, M; Halabi, M; Paz, O; Piltz, X; Targetti, M; Metra, M; Canepa, M; Musumeci, B; Emdin, M; Amin, A; Knackstedt, C; Wojakowski, W; Dudek, D; Toste, A; Bastos, JM; Pavia, PG; Gimeno Blanes, JR; Hidalgo Urbano, RJ; Alvarez, AG; Rincón Diaz, LM; Ripoll Vera, TV; Coats, C; Cooper, R; Mahmod, M; Bradlow, W; Pantazis, A; Tome Esteban, MT; Marian, A; Owens, D; Wheeler, M; McGrew, F; Bach, R; Wever-Pinzon, O; Collado, E; Hannawi, B; Geske, J; Sarswat, N; Ahmad, F; Markowitz, J; Lakdawala, N; Jani, S; Brinkley, DM; Asher, C; Emani, S; Sharma, A; Fermin, D; Lyle, M; Raymer, D; Darlington, A; Nielsen, C; Martinez, M; Desai, M; Kelly, J; Sen, S; Bering, P; Maurer, M; Mitter, S; Hussain, Z; Naidu, S; Enciso, JS; Donal, E; Hagege, A; Brandenburg, S; Raman, B; Afshar, K; Alsidawi, S; Drakos, S; Moss, N; Ravi, S; Rowin, E; Rader, AT; Weiner, S; Zenker, M |
| Publisher Information: | Elsevier BV |
| Publication Year: | 2026 |
| Collection: | St George's University of London: Repository |
| Description: | Background Disopyramide, used in obstructive hypertrophic cardiomyopathy (oHCM) for its negative inotropic properties mediated by its reduction in cytosolic calcium, has been recommended for decades as an option to relieve resistant obstruction. Aficamten is a selective cardiac myosin inhibitor that reduces hypercontractility directly by reducing myosin-actin interaction. Objectives This study aims to investigate the safety and efficacy of concomitant use and withdrawal of disopyramide in patients with symptomatic oHCM receiving aficamten. Methods Patients with oHCM enrolled in REDWOOD-HCM Cohort 3 (open-label), SEQUOIA-HCM (placebo-controlled), and FOREST-HCM (open-label) were analyzed. The authors identified 4 groups, each with patients symptomatic despite background therapy with disopyramide who received: 1) disopyramide plus aficamten and subsequent aficamten withdrawal per protocol (Diso-Afi Withdrawal); 2) disopyramide plus placebo (Diso-Pbo); 3) aficamten plus disopyramide with subsequent disopyramide withdrawal (Afi-Diso Withdrawal); and 4) continued both disopyramide and aficamten (Diso+Afi Continuous). Assessments were performed at baseline, after aficamten or placebo add-on therapy, and after washout (except at week 24 for Diso+Afi Continuous group). Results Overall, 50 unique patients from 3 trials enrolled, resulting in 93 subjects (segments) across 4 groups: Diso-Afi Withdrawal (n = 29), Diso-Pbo (n = 20), Afi-Diso Withdrawal (n = 17), and Diso+Afi Continuous (n = 27); mean disopyramide dose was 331 ± 146 mg/d. The addition of aficamten to disopyramide alleviated left ventricular outflow tract (LVOT) obstruction (resting: change [Δ] in least squares mean −27.0 ± 3.6, Valsalva: Δ least squares mean −39.2 ± 5.0, both P < 0.0001), symptoms (≥1 NYHA functional class improvement: 77.8% [95% CI: 61.0-94.5]; P < 0.0001; Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score: 12.3 ± 3.3 [P < 0.001]), and reduced N-terminal pro–B-type natriuretic peptide ratio: 0.35 [95% CI: 0.26-0.48]; P ... |
| Document Type: | article in journal/newspaper |
| File Description: | application/pdf; application/vnd.openxmlformats-officedocument.wordprocessingml.document |
| Language: | English |
| ISSN: | 2213-1779 |
| Relation: | https://openaccess.sgul.ac.uk/id/eprint/117847/1/1-s2.0-S2213177925002434-main.pdf; https://openaccess.sgul.ac.uk/id/eprint/117847/2/1-s2.0-S2213177925002434-mmc1.docx; Masri, A; Maron, MS; Abraham, TP; Nassif, ME; Barriales-Villa, R; Bilen, O; Coats, CJ; Elliott, P; Garcia-Pavia, P; Massera, D; et al. Masri, A; Maron, MS; Abraham, TP; Nassif, ME; Barriales-Villa, R; Bilen, O; Coats, CJ; Elliott, P; Garcia-Pavia, P; Massera, D; Olivotto, I; Oreziak, A; Owens, AT; Saberi, S; Solomon, SD; Tower-Rader, A; Heitner, SB; Jacoby, DL; Melloni, C; Wei, J; Sherrid, MV; Olivotto, I; Michels, M; Barriales-Villa, R; Garcia-Pavia, P; Abraham, TP; Choudhury, L; Kramer, C; Lakdawala, NK; Maron, MS; Masri, A; Nagueh, SF; Owens, AT; Rader, F; Saberi, S; Sherrid, MV; Symanski, JD; Tower-Rader, A; Turer, A; Wang, A; Wong, T; Zhang, Y; Yang, H; Shao, C; Yuan, Z; Zeng, Q; Li, X; Ma, C; Wang, Y; Shu, Y; Chen, M; Tao, L; Li, X; Wang, J; Yu, Z; Cheng, X; Hong, K; Zemanek, D; Bundgaard, H; Thune, J; Jensen, M; Mogensen, J; Hagège, A; Habib, G; Charron, P; Lhermusier, T; Trochu, J-N; Reant, P; Logeart, D; Mitrovic, V; Bekfani, T; Edelman, F; Seidler, T; Meder, B; Schulze, PC; Stoerk, S; Rassaf, T; Merkely, B; Zfat-Zwas, D; Arad, M; Halabi, M; Paz, O; Piltz, X; Targetti, M; Metra, M; Canepa, M; Musumeci, B; Emdin, M; Michels, M; Amin, A; Knackstedt, C; Oreziak, A; Wojakowski, W; Dudek, D; Toste, A; Bastos, JM; Barriales-Villa, R; Pavia, PG; Gimeno Blanes, JR; Hidalgo Urbano, RJ; Alvarez, AG; Rincón Diaz, LM; Ripoll Vera, TV; Elliott, P; Coats, C; Cooper, R; Mahmod, M; Bradlow, W; Pantazis, A; Tome Esteban, MT; Masri, A; Nassif, ME; Marian, A; Owens, D; Wheeler, M; McGrew, F; Bach, R; Wever-Pinzon, O; Collado, E; Turer, A; Hannawi, B; Geske, J; Owens, AT; Symanski, JD; Kramer, C; Sarswat, N; Ahmad, F; Abraham, TP; Markowitz, J; Lakdawala, N; Choudhury, L; Jani, S; Brinkley, DM; Bilen, O; Asher, C; Emani, S; Sharma, A; Fermin, D; Lyle, M; Raymer, D; Darlington, A; Maron, MS; Nielsen, C; Wang, A; Nagueh, SF; Martinez, M; Desai, M; Tower-Rader, A; Kelly, J; Rader, F; Sen, S; Bering, P; Maurer, M; Mitter, S; Sherrid, MV; Wong, T; Hussain, Z; Saberi, S; Naidu, S; Enciso, JS; Zemanek, D; Bundgaard, H; Jensen, M; Mogensen, J; Thune, J; Donal, E; Habib, G; Hagege, A; Logeart, D; Reant, P; Trochu, J-N; Brandenburg, S; Edelman, F; Meder, B; Rassaf, T; Schulze, PC; Stoerk, S; Merkely, B; Arad, M; Halabi, M; Piltz, X; Zfat-Zwas, D; Emdin, M; Musumeci, B; Knackstedt, C; Michels, M; Oreziak, A; Wojakowski, W; Bastos, JM; Toste, A; Bradlow, W; Coats, C; Cooper, R; Elliott, P; Pantazis, A; Raman, B; Tome Esteban, MT; Abraham, TP; Afshar, K; Alsidawi, S; Bering, P; Bilen, O; Brinkley, DM; Choudhury, L; Darlington, A; Desai, M; Drakos, S; Hannawi, B; Hussain, Z; Kelly, J; Kramer, C; Lakdawala, N; Martinez, M; Masri, A; Mitter, S; Moss, N; Nagueh, SF; Naidu, S; Nassif, ME; Owens, AT; Rader, F; Ravi, S; Rowin, E; Saberi, S; Sen, S; Sherrid, MV; Enciso, JS; Rader, AT; Turer, A; Wang, A; Weiner, S; Wong, T; Zenker, M (2026) Concomitant Aficamten and Disopyramide in Symptomatic Obstructive Hypertrophic Cardiomyopathy. JACC: Heart Failure, 14 (2). p. 102441. ISSN 2213-1779 https://doi.org/10.1016/j.jchf.2025.03.008 SGUL Authors: Tome, Maria Teresa |
| DOI: | 10.1016/j.jchf.2025.03.008 |
| Availability: | https://openaccess.sgul.ac.uk/id/eprint/117847/; https://doi.org/10.1016/j.jchf.2025.03.008 |
| Rights: | cc_by_nc_nd_4 |
| Accession Number: | edsbas.B4E810C5 |
| Database: | BASE |