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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]
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“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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“Disopyramide, a negative inotropic agent, when added to a β-blocker may reduce symptoms further in patients with LVOT obstruction.(231) L-type calcium channel blockers, such as verapamil or diltiazem, may be beneficial in patients who do not tolerate or respond to β-blockers.”
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“Disopyramide is the most reliable drug for reducing outflow gradients at rest in HCM, although long-term use may be limited by parasympathetic side effects (95).”
BackgroundSelf-citation2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy
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“Disopyramide may be added to reduce symptoms in patients with LVOTO via its negative inotropic effect [56].”
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“High-dose β-blocker IA antiarrhythmic, negative inotropy; cave: QTc prolongation (18,19,32,176)”
BackgroundTargets for therapy in sarcomeric cardiomyopathies
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BackgroundEfthimiadis, G. K., Pagourelias, E. D., Parcharidou, D. G., Gossios, T. D., Kamperidis, V., Theofilogiannakos, E. K., Pappa, Z., Meditskou, S., Hadjimiltiades, S., Pliakos, C. I., et al. (2013) · Circulation Journal · doi:10.1253/circj.cj-12-1561 · Cited by 102
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“doses (430–500 mg) of this drug.(4,9) Nevertheless, disopyramide does have significant electrophysiological effects.”
BackgroundResultGersh, B. J., Maron, B. J., Bonow, R. O., Dearani, J. A., Fifer, M. A., Link, M. S., Naidu, S. S., Nishimura, R. A., Ommen, S. R., Rakowski, H., et al. (2011) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/j.jtcvs.2011.10.019 · Cited by 85
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“In a multicenter study of disopyramide, with a relatively low dosage, there was a clear trend toward lower sudden cardiac death mortality in disopyramide-treated patients with HCM (5).”
BackgroundHypertrophic Cardiomyopathy in 2012
Ho, C. Y. (2012) · Circulation · doi:10.1161/circulationaha.110.017277 · Cited by 80
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Macintyre, C. J., & Lakdawala, N. K. (2016) · Circulation · doi:10.1161/circulationaha.115.015085 · Cited by 73
“risk of ventricular arrhythmia or sudden death.(18) However, disopyramide monotherapy, without β-blockers, diltiazem,”
BackgroundDimitrow, P. P., Bober, M., Michałowska, J., & Sorysz, D. (2009) · Echocardiography · doi:10.1111/j.1540-8175.2008.00851.x · Cited by 74
New-Onset Atrial Fibrillation After Cardiac Surgery: Pathophysiology, Prophylaxis, and Treatment
Ломиворотов, В. В., Efremov, S. M., Pokushalov, E. A., & Karaskov, A. M. (2015) · Journal of Cardiothoracic and Vascular Anesthesia · doi:10.1053/j.jvca.2015.08.003 · Cited by 73
Reflections of Inflections in Hypertrophic Cardiomyopathy
Sherrid, M. V., Wever‐Pinzon, O., Shah, A., & Chaudhry, F. A. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.03.052 · Cited by 70
Most Fully Informed Patients Choose Septal Ablation Over Septal Myectomy
Fifer, M. A. (2007) · Circulation · doi:10.1161/circulationaha.107.688135 · Cited by 68
Hypertrophic cardiomyopathy in childhood and adolescence – strategies to prevent sudden death
Östman‐Smith, I. (2010) · Fundamental and Clinical Pharmacology · doi:10.1111/j.1472-8206.2010.00869.x · Cited by 64
Left ventricular outflow tract obstruction in hypertrophic cardiomyopathy: past, present and future
Ommen, S. R., Shah, P. M., & Tajik, A. J. (2008) · Heart · doi:10.1136/hrt.2008.154435 · Cited by 63
Hypertrophic Cardiomyopathy: New Concepts and Therapies
Maron, B. J., Rowin, E. J., & Maron, M. S. (2022) · Annual Review of Medicine · doi:10.1146/annurev-med-042220-021539 · Cited by 58
Pharmacological Management of Hypertrophic Cardiomyopathy: From Bench to Bedside
Palandri, C., Santini, L., Argirò, A., Margara, F., Doste, R., Bueno‐Orovio, A., Olivotto, I., & Coppini, R. (2022) · Drugs · doi:10.1007/s40265-022-01728-w · Cited by 58
“More recently, Sherrid and co-workers studied the safety and efficacy of long-term treatment with disopyramide in oHCM patients [41].”
BackgroundEvolving Contemporary Management of Atrial Fibrillation in Hypertrophic Cardiomyopathy
Rowin, E. J., Link, M. S., Maron, M. S., & Maron, B. J. (2023) · Circulation · doi:10.1161/circulationaha.123.065037 · Cited by 61
Ferrantini, C., Pioner, J. M., Mazzoni, L., Gentile, F. R., Tosi, B., Rossi, A., Belardinelli, L., Tesi, C., Palandri, C., Matucci, R., et al. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14223 · Cited by 56
“Through the reduction of LV contractility, disopyramide slows down the acceleration of flow in the LVOT during systole, thus delaying or abolishingmitral-septal contact (Sherrid et al., 2005).”
BackgroundLeft Ventricular Hypertrophy: Etiology-Based Therapeutic Options
Sayın, B. Y., & Oto, A. (2022) · Cardiology and Therapy · doi:10.1007/s40119-022-00260-y · Cited by 60
“Since persistent and paroxysmal AF are risk factors for thromboembolism, longterm anticoagulation is necessary in clinical and subclinical AF (detected by an internal or external cardiac device) [50, 56].”
BackgroundAntunes, M. D. O., & Scudeler, T. L. (2020) · IJC Heart & Vasculature · doi:10.1016/j.ijcha.2020.100503 · Cited by 53
“Disopyramide, an antiarrhythmic drug, has an important negative inotropic effect that, in obstructive forms, leads to a decrease or even disappearance of the LVOT gradient, with improvement of symptoms [65].”
BackgroundThin filament cardiomyopathies: A review of genetics, disease mechanisms, and emerging therapeutics
Keyt, L. K., Duran, J. M., Bui, Q. M., Chen, C., Miyamoto, M. I., Enciso, J. S., Tardiff, J. C., & ADLER, E. D. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.972301 · Cited by 50
“The class Ia antiarrhythmic, disopyramide, has sarcomere-independent negative inotropic effects and is effective in reducing both obstruction and arrhythmic activity (159, 160).”
BackgroundDrug Therapy for Hypertrophic Cardiomypathy: Physiology and Practice
Sherrid, M. V. (2016) · Current Cardiology Reviews · doi:10.2174/1573403x1201160126125403 · Cited by 50
“Disopyramide is not a dangerous drug in obstructive HCM [1, 2, 39, 42].”
Pathophysiology and Treatment of Hypertrophic Cardiomyopathy
Sherrid, M. V. (2006) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2006.08.001 · Cited by 51
“We also avoid macrolide antibiotics.(111,127) Because disopyramide is a type I antiarrhyth-”
Hypertrophic cardiomyopathy: current understanding and treatment objectives
Soor, G. S., Luk, A. O. Y., Ahn, E., Abraham, J. R., Woo, A., Ralph-Edwards, A. C., & BUTANY, J. W. (2008) · Journal of Clinical Pathology · doi:10.1136/jcp.2008.061655 · Cited by 51
Contemporary treatment of hypertrophic cardiomyopathy.
Marian, A. J. (2009) · PubMed Central · Cited by 50
Hypertrophic cardiomyopathy and sudden cardiac death
Stroumpoulis, K. (2010) · World Journal of Cardiology · doi:10.4330/wjc.v2.i9.289 · Cited by 48
Miller, C. A. S., Maron, M. S., Estes, N. A. M., Price, L. L., Rowin, E. J., Maron, B. J., & Link, M. S. (2019) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2019.02.051 · Cited by 47
2020 Clinical practice guidelines for Hypertrophic cardiomyopathy
Габрусенко, С. А., Gudkova, A. Y., Koziolova, N. A., Alexandrova, S. А., Berseneva, M., Гордеев, М. Л., Sl, D., Zaklyazminskaya, E. V., Irtyuga, O. B., Kaplunova, V. Y., et al. (2021) · Russian Journal of Cardiology · doi:10.15829/1560-4071-2021-4541 · Cited by 56
Hegde, S. M., Claggett, B. L., Wang, X., Jering, K., Prasad, N., Roshanali, F., Masri, A., Nassif, M. E., Barriales-Villa, R., Abraham, T. P., et al. (2024) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2024.08.002 · Cited by 47
Alhaj, E. K., Kim, B., Cantales, D., Uretsky, S., Chaudhry, F. A., & Sherrid, M. V. (2013) · Journal of the American Society of Echocardiography · doi:10.1016/j.echo.2013.02.007 · Cited by 45
Hypertrophic cardiomyopathy: diagnosis, risk stratification and treatment
Jacoby, D. L., DePasquale, E. C., & McKenna, W. J. (2012) · Canadian Medical Association Journal · doi:10.1503/cmaj.120138 · Cited by 44
“Disopyramide should be considered for patients with obstructive hypertrophic cardiomyopathy before more invasive interventions.(62) It should not, however, be administered with other antiarrhythmic drugs (e.”
BackgroundFamilial screening and genetic counselling in hypertrophic cardiomyopathy: the Rotterdam experience
Michels, M., Hoedemaekers, Y. M., Kofflard, M. J. M., Frohn-Mulder, I. M. E., Dooijes, D., Majoor‐Krakauer, D. F., & ten Cate, F. J. (2007) · Netherlands Heart Journal · doi:10.1007/bf03085978 · Cited by 43
Pacing for hypertrophic obstructive cardiomyopathy: an update and future directions
Daubert, J., Gadler, F., Mabo, P., & Linde, C. M. (2017) · EP Europace · doi:10.1093/europace/eux131 · Cited by 41
Management of Hypertrophic Cardiomyopathy
Enriquez, A. D., & Goldman, M. E. (2014) · Annals of Global Health · doi:10.1016/j.aogh.2013.12.004 · Cited by 42
Atrial Fibrillation in Hypertrophic Cardiomyopathy
Weissler‐Snir, A., Saberi, S., Wong, T. C., Pantazis, A. A., OWENS, A. T., Leunig, A., Alvarez, C., & Rader, F. (2024) · JACC Advances · doi:10.1016/j.jacadv.2024.101210 · Cited by 40
Advances in medical treatment of hypertrophic cardiomyopathy
Hamada, M., Ikeda, S., & Shigematsu, Y. (2014) · Journal of Cardiology · doi:10.1016/j.jjcc.2014.02.022 · Cited by 37
Implications of Arrhythmias and Prevention of Sudden Death in Hypertrophic Cardiomyopathy
Adabağ, S., & Maron, B. J. (2007) · Annals of Noninvasive Electrocardiology · doi:10.1111/j.1542-474x.2007.00157.x · Cited by 40
Bogachev-Prokophiev, A. V., Afanasyev, A. V., Иванович, Ж. С., Pivkin, A. N., Фоменко, М. С., Махарамович, Ш. Р., & Karaskov, A. M. (2017) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/j.jtcvs.2017.08.063 · Cited by 38
Characteristics and Outcomes of Elderly Patients With Hypertrophic Cardiomyopathy
Alashi, A., Smedira, N. G., Popović, Z., Fava, A. M., Thamilarasan, M., Kapadia, S. R., Wierup, P. N., Lever, H. M., & Desai, M. Y. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.120.018527 · Cited by 38
Surgical management of obstructive hypertrophic cardiomyopathy: the gold standard
Brown, M. L., & Schaff, H. V. (2008) · Expert Review of Cardiovascular Therapy · doi:10.1586/14779072.6.5.715 · Cited by 38
Antihypertensive Therapy in Hypertrophic Cardiomyopathy
Argulian, E., Messerli, F. H., Aziz, E. F., Winson, G., Agarwal, V., Kaddaha, F., Kim, B., & Sherrid, M. V. (2013) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2012.12.026 · Cited by 37
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Pacing for drug-refractory or drug-intolerant hypertrophic cardiomyopathy
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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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