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Multicenter study of the efficacy and safety of disopyramide in obstructive hypertrophic cardiomyopathy
Open accessAbstract
Objectives In this study we assessed the long-term efficacy and safety of disopyramide for patients with obstructive hypertrophic cardiomyopathy (HCM).Background It has been reported that disopyramide may reduce left ventricular outflow gradient and improve symptoms in patients with HCM. However, long-term efficacy and safety of disopyramide has not been shown in a large cohort.Methods Clinical and echocardiographic data were evaluated in 118 obstructive HCM patients treated with disopyramide at 4 HCM treatment centers. Mortality in the disopyramide-treated patients was compared with 373 obstructive HCM patients not treated with disopyramide.Results Patients were followed with disopyramide for 3.1 +/- 2.6 years; dose 432 +/- 181 mg/day (97% also received beta-blockers). Seventy-eight patients (66%) were maintained with disopyramide without the necessity for major non-pharmacologic intervention with surgical myectomy, alcohol ablation, or pacing; outflow gradient at rest decreased from 75 +/- 33 to 40 +/- 32 mm Hg (p < 0.0001) and mean New York Heart Association functional class from 2.3 +/- 0.7 to 1.7 +/- 0.6 (p < 0.0001). Forty other patients (34%) could not be satisfactorily managed with disopyramide and required major invasive interventions because of inadequate symptom and gradient control or vagolytic side effects. All-cause annual cardiac death rate between disopyramide and non-disopyramide-treated patients did not differ significantly, 1.4% versus 2.6%/year (p = 0.07). There was also no difference in sudden death rate, 1.0%/year versus 1.8%/year (p = 0.08).Conclusions Two-thirds of obstructed HCM patients treated with disopyramide could be managed medically with amelioration of symptoms and about 50% reduction in subaortic gradient over >/=3 years. Disopyramide therapy does not appear to be proarrhythmic in HCM and should be considered before proceeding to surgical myectomy or alternate strategies.
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“Disopyramide has been shown in retrospective studies to be safe and associated with an improvement in both LVOT gradient and symptoms when used in combination with β blockers or non-dihydropyridine CCBs.”
From Current management of hypertrophic cardiomyopathy (2025) · cites this paper as [30]
Experimental — accuracy not yet measuredIn the citing paper
“has been shown to reduce LV outflow gradient and improve symptoms in patients with hypertrophic cardiomyopathy.[662][663][664]”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [662]
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“Finally, although disopyramide ameliorates symptoms and reduces LVOT obstruction in HCM, these effects are attributed to its negative inotropic action rather than late sodium block [171].”
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“In a multicenter study of disopyramide from 4 institutions, we found that two-thirds of patients could be successfully managed without the need for septal reduction.(22) In these patients, resting gradients were reduced by half with a concomitant relief of symptoms (Fig 9).”
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“Although disopyramide may be useful to mitigate LVOTO, its effects on SR maintenance have been poorly investigated in the context of HCM.(11) In a small, double‐blind crossover study, sotalol significantly suppressed supraventricular arrhythmias but its long‐term safety and efficacy are unknown.”
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Litt, M. J., Ali, A., & Reza, N. (2023) · Vascular Health and Risk Management · doi:10.2147/vhrm.s365001 · Cited by 29
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“These findings are in line with the drug physiopathological effect, mainly driven by its negative inotropic effect, which is the main mechanistic driver of reduction in LVOT gradients; it is less potent in patients who demonstrate less HCM-induced hypercontractility [6,7].”
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“Importantly, in the vast clinical experience on the use of disopyramide for LV outflow tract obstruction, the risk of sudden cardiac death (SCD) does not appear to be increased [33].”
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“The maximum number of patients in a single prospective study was 118, in a multicenter registry evaluating the efficacy and safety of disopyramide.(11) Overall, these data eloquently demonstrate how poorly pharmacological research in HCM compares with that performed in other, more prevalent conditions such as coronary…”
Sudden Cardiac Death in Genetic Cardiomyopathies
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Alcohol Septal Ablation: An Option on the Rise in Hypertrophic Obstructive Cardiomyopathy
Arévalos, V., Rodríguez-Arias, J. J., Brugaletta, S., Micari, A., Costa, F., Freixa, X., Masotti, M., Sabaté, M., & Regueiro, A. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10112276 · Cited by 15
“Other possibilities are verapamil or disopyramide in combination with beta blockers; however, this combination is usually not tolerated due to the anticholinergic side effects [6] In patients with HOCM who remain severely symptomatic despite guideline-directed medical treatment, invasive treatment or septal reduction…”
BackgroundKitai, T., Xanthopoulos, A. V., Nakagawa, S., Ishii, N., Amano, M., Triposkiadis, F. K., & Izumi, C. (2022) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd9060169 · Cited by 15
“These drugs have negative inotropic effects and can decrease resting and provoked LV obstruction [40,66,67].”
BackgroundExperimental models of inherited cardiomyopathy and its therapeutics
Nonaka, M. (2014) · World Journal of Cardiology · doi:10.4330/wjc.v6.i12.1245 · Cited by 18
Maron, B. J., Maron, M. S., Sherrid, M. V., & Rowin, E. J. (2022) · Journal of the American Heart Association · doi:10.1161/jaha.121.024566 · Cited by 15
Cardiac myosin inhibitors in hypertrophic cardiomyopathy
Lim, J., & Kim, H. (2025) · Journal of Cardiovascular Imaging · doi:10.1186/s44348-025-00052-7 · Cited by 14
Does Surgical Relief of Obstruction Improve Prognosis for Hypertrophic Cardiomyopathy?
Ross, R. E., Sherrid, M. V., Casey, M. M., Swistel, D. G., & Balaram, S. K. (2012) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2012.03.005 · Cited by 14
“To date, there is no evidence to suggest that septal myectomy improves survival in patients who achieve relief of gradient and symptoms through pharmacologic therapy or those who have only mild symptoms.(19,20) Our database of patients at St Luke's–Roosevelt Hospital shows that patients with symptomatic obstructive HC…”
BackgroundMethodRothman, R. D., Baggish, A. L., O’Callaghan, C., Lowry, P. A., Bhatt, A. B., MacRae, C. A., Yannekis, G., Sanborn, D. M. Y., Mela, T., Yeh, R. W., et al. (2012) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2012.05.056 · Cited by 14
Pysz, P., Rajtar-Salwa, R., Smolka, G. A., Olivotto, I., Wojakowski, W., & Dimitrow, P. P. (2021) · Kardiologia Polska · doi:10.33963/kp.a2021.0064 · Cited by 14
Lansoprazole precipitated QT prolongation and torsade de pointes associated with disopyramide
Asajima, H., Saito, N., Ohmura, Y., & Ohmura, K. (2011) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-011-1119-z · Cited by 14
Cheitlin, M. D. (2006) · Yearbook of Cardiology · doi:10.1016/s0145-4145(07)70220-4 · Cited by 14
Jensen, M. K., Faber, L., Liebregts, M., Januška, J., Krejčí, J., Bartel, T., Cooper, R. M., Dąbrowski, M., Hansen, P. R., Almaas, V. M., et al. (2018) · European Heart Journal - Quality of Care and Clinical Outcomes · doi:10.1093/ehjqcco/qcy049 · Cited by 14
Lan, H., Xu, Q., El‐Battrawy, I., Zhong, R., Li, X., Lang, S., Cyganek, L., Borggrefe, M. M., Zhou, X., & Akın, İ. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.554422 · Cited by 14
McKenna, W. J., & Sen‐Chowdhry, S. (2008) · Revista Española de Cardiología (English Edition) · doi:10.1016/s1885-5857(09)60050-5 · Cited by 14
“Effective, evidencebased pharmacological therapy began with propranolol(35); today, beta-blockers are still the mainstay of drug treatment for exertional outflow obstruction, while a multi-centre collaborative study has demonstrated the efficacy and safety of disopyramide in patients with significant resting gradients…”
BackgroundSirak, T. E., & Sherrid, M. V. (2008) · Chest · doi:10.1378/chest.07-1188 · Cited by 13
Self-citationSawan, M. A., Prabakaran, S., D'Souza, M. S., Behbahani‐Nejad, O., Gold, M. E., Williams, B. R., & Bilen, O. (2024) · Clinical Cardiology · doi:10.1002/clc.24207 · Cited by 13
“22 Most recently, the safety of disopyramide initiation was studied in the outpatient setting.”
BackgroundLebowitz, S., Kowalewski, M., Raffa, G. M., Chu, D., Greco, M., Gandolfo, C. M., Mignosa, C., Lorusso, R., Suwalski, P., & Pilato, M. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11123405 · Cited by 14
New trends in treatment of hypertrophic cardiomyopathy
Hagège, A. A., & Desnos, M. (2009) · Archives of cardiovascular diseases · doi:10.1016/j.acvd.2009.03.008 · Cited by 13
Alcohol septal ablation in hypertrophic obstructive cardiomyopathy.
Rigopoulos, A. G., Panou, F., Kremastinos, D. T., & Seggewiß, H. (2009) · PubMed · Cited by 13
Topriceanu, C., Field, E., Boleti, O., Cervi, E., Kaski, J. P., & Norrish, G. (2022) · International Journal of Cardiology · doi:10.1016/j.ijcard.2022.09.044 · Cited by 12
Obstructive Hypertrophic Cardiomyopathy: A Review of New Therapies
Mehra, N. S., Ali, A. H., & Desai, M. Y. (2023) · Future Cardiology · doi:10.2217/fca-2023-0056 · Cited by 12
Dicorato, M. M., Citarelli, G., Mangini, F., Alemanni, R., Albanese, M., Cicco, S., Greco, C. A., Forleo, C., Basile, P., Carella, M. C., et al. (2025) · Biomedicines · doi:10.3390/biomedicines13051256 · Cited by 13
“The limitations of disopyramid include its gradual loss of efficacy over time [30,31], the absence of a long-acting formulation, necessitating frequent dosing (every 6–8 h), which can cause patient discomfort, the potential for QTc prolongation requiring ECG monitoring, anticholinergic effects…”
Mateo, J. J. S., Molina, M. S., & Gimeno, J. R. (2017) · Medicina Clínica · doi:10.1016/j.medcli.2017.09.013 · Cited by 12
Maron, B. J., Rowin, E. J., & Maron, M. S. (2024) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2023.10.073 · Cited by 11
Insights and challenges in hypertrophic cardiomyopathy, 2012
Sen‐Chowdhry, S., Tome, M., & McKenna, W. J. (2012) · Herzschrittmachertherapie + Elektrophysiologie · doi:10.1007/s00399-012-0227-5 · Cited by 11
State-of–the-Art Management of Hypertrophic Cardiomyopathy in Children
Berger, S., Dhala, A. A., & Dearani, J. A. (2009) · Cardiology in the Young · doi:10.1017/s1047951109991648 · Cited by 11
“are beneficial effects of disopyramide in the presence of severe symptomatology due to an obstructed left ventricular outflow tract, although the anticholinergic side effects limit its use.(13) Because disopyramide can accelerate atrioventricular nodal conduction, it should be used in conjunction with a beta-blocker.”
BackgroundEarly post-septal myectomy outcomes for hypertrophic obstructive cardiomyopathy
Afanasyev, A. V., Bogachev-Prokophiev, A. V., Иванович, Ж. С., Сергеевич, З. А., Budagaev, S. A., Shajahmetova, S. V., Nazarov, V. M., Иванович, Д. И., Махарамович, Ш. Р., Pivkin, A. N., et al. (2021) · Asian Cardiovascular and Thoracic Annals · doi:10.1177/02184923211056133 · Cited by 11
Antiarrhythmic Drug Therapy for Atrial Fibrillation
Sardar, M. R., Saeed, W., & Kowey, P. R. (2014) · Cardiology Clinics · doi:10.1016/j.ccl.2014.07.012 · Cited by 11
McKenna, W. J., & Sen‐Chowdhry, S. (2008) · Revista Española de Cardiología · doi:10.1016/s0300-8932(08)75730-0 · Cited by 11
Minami, Y., Kajimoto, K., Kawana, M., Hagiwara, N., & Sherrid, M. V. (2008) · International Journal of Cardiology · doi:10.1016/j.ijcard.2008.11.088 · Cited by 11
“Two-thirds of patients who would otherwise need septal reduction therapy were successfully managed medically by the combination of disopyramide and beta-blockers after N3 years [5].”
BackgroundCurrent management of hypertrophic cardiomyopathy
COATS, C. J., & Elliot, P. M. (2008) · Current Treatment Options in Cardiovascular Medicine · doi:10.1007/s11936-008-0042-9 · Cited by 11
Bjerregaard, L., Dybro, A. M., Saaby, L., Poulsen, S. H., Rasmussen, T. R., & Jensen, M. S. K. (2026) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2025.11.028 · Cited by 10
Mitral Valve Interventions for Hypertrophic Obstructive Cardiomyopathy
Shuvy, M., Postell, Y. Y., Carasso, S., Marmor, D. B., Strauss, B. H., Maisano, F., & Lapenna, E. (2023) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2023.12.009 · Cited by 10
Metadata
- Authors
- Sherrid, M. V., Barac, I., McKenna, W. J., Elliott, P. M., Dickie, S., Chojnowska, L., Casey, S., & Maron, B. J.
- Affiliations
- St. Luke's-Roosevelt Hospital Center (US)
- St George's, University of London (GB)
- Institute of Cardiology (PL)
- Minneapolis Heart Institute Foundation (US)
- Corresponding author
- Sherrid, Mark V.
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2005-04
- Volume
- 45
- Issue
- 8
- Pages
- 1251-1258
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W1992100033
- Cited by
- 410
- References
- 52
- Citations by year
- 2026: 12 · 2025: 35 · 2024: 34 · 2023: 24 · 2022: 23 · 2021: 23 · 2020: 20 · 2019: 14 · 2018: 19 · 2017: 16 · 2016: 15 · 2015: 17 · 2014: 27 · 2013: 18 · 2012: 22
- FWCI
- 8.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Immunology Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- disopyramide, hypertrophic obstructive cardiomyopathy, left ventricular outflow tract gradient, long-term efficacy, drug safety, sudden cardiac death, cardiac mortality, drug-induced arrhythmia, beta-blockers, myectomy, alcohol septal ablation, NYHA functional class
- MeSH terms
- Administration, Oral, Adrenergic beta-Antagonists, Anti-Arrhythmia Agents, Cardiomyopathy, Hypertrophic, Disopyramide, Echocardiography, Female, Humans, Male, Middle Aged, Myocardial Contraction, Safety, Death, Sudden, Cardiac, Treatment Outcome
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