Display options
Cite
Coppini R, Ferrantini C, Pioner JM, et al. Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy: A Translational Study. JACC Basic Transl Sci. 2019;4(7):795-813doi: 10.1016/j.jacbts.2019.06.004.
Coppini, R., Ferrantini, C., Pioner, J. M., Santini, L., Wang, Z. J., Palandri, C., Scardigli, M., Vitale, G., Sacconi, L., Stefàno, P., Flink, L., Riedy, K., Pavone, F. S., Cerbai, E., Poggesi, C., Mugelli, A., Bueno-Orovio, A., Olivotto, I., & Sherrid, M. V. (2019). Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy: A Translational Study. JACC. Basic to translational science, 4(7), 795-813. https://doi.org/10.1016/j.jacbts.2019.06.004
Coppini, Raffaele, et al. "Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy: A Translational Study." JACC. Basic to translational science vol. 4,7 (2019): 795-813. doi: https://doi.org/10.1016/j.jacbts.2019.06.004
Coppini R, Ferrantini C, Pioner JM, Santini L, Wang ZJ, Palandri C, Scardigli M, Vitale G, Sacconi L, Stefàno P, Flink L, Riedy K, Pavone FS, Cerbai E, Poggesi C, Mugelli A, Bueno-Orovio A, Olivotto I, Sherrid MV. Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy: A Translational Study. JACC Basic Transl Sci. 2019 Oct 09;4(7):795-813. doi: 10.1016/j.jacbts.2019.06.004. eCollection 2019 Nov. PMID: 31998849; PMCID: PMC6978554.
Copy Download .nbib Format: NLM
Share it on

JACC Basic Transl Sci. 2019 Oct 09;4(7):795-813. doi: 10.1016/j.jacbts.2019.06.004. eCollection 2019 Nov.

Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy: A Translational Study.

JACC. Basic to translational science

Raffaele Coppini, Cecilia Ferrantini, Josè Manuel Pioner, Lorenzo Santini, Zhinuo J Wang, Chiara Palandri, Marina Scardigli, Giulia Vitale, Leonardo Sacconi, Pierluigi Stefàno, Laura Flink, Katherine Riedy, Francesco Saverio Pavone, Elisabetta Cerbai, Corrado Poggesi, Alessandro Mugelli, Alfonso Bueno-Orovio, Iacopo Olivotto, Mark V Sherrid

Affiliations

  1. Department NeuroFarBa, University of Florence, Florence, Italy.
  2. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
  3. Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy.
  4. Department of Computer Sciences, University of Oxford, Oxford, United Kingdom.
  5. European Laboratory for Nonlinear Spectroscopy (LENS), University of Florence, Sesto Fiorentino, Italy and National Institute of Optics, National Research Council, Florence, Italy.
  6. Division of Cardiology, San Francisco Veterans Affairs Medical Center and University of California-San Francisco, San Francisco, California.
  7. Hypertrophic Cardiomyopathy Program, New York University Langone Health, New York, New York.

PMID: 31998849 PMCID: PMC6978554 DOI: 10.1016/j.jacbts.2019.06.004

Abstract

Disopyramide is effective and safe in patients with obstructive hypertrophic cardiomyopathy. However, its cellular and molecular mechanisms of action are unknown. We tested disopyramide in cardiomyocytes from the septum of surgical myectomy patients: disopyramide inhibits multiple ion channels, leading to lower Ca transients and force, and shortens action potentials, thus reducing cellular arrhythmias. The electrophysiological profile of disopyramide explains the efficient reduction of outflow gradients but also the limited prolongation of the QT interval and the absence of arrhythmic side effects observed in 39 disopyramide-treated patients. In conclusion, our results support the idea that disopyramide is safe for outpatient use in obstructive patients.

© 2019 The Authors.

Keywords: AP, action potential; DAD, delayed afterdepolarization; EAD, early afterdepolarization; ECG, electrocardiography; HCM, hypertrophic cardiomyopathy; ICa-L, L-type Ca current; IK, delayed-rectifier K current; INaL, late Na current; LVOT, left ventricular outflow tract; NCX, Na+/Ca2+ exchanger; QT interval; RyR, ryanodine receptor; SR, sarcoplasmic reticulum; action potentials; arrhythmias; diastolic dysfunction; hERG, human ether-à-go-go-related gene; hypertrophic cardiomyopathy; pCa, Ca activation level; safety

References

  1. Cardiovasc Res. 2017 Dec 1;113(14):1743-1752 - PubMed
  2. J Am Heart Assoc. 2017 Jul 22;6(7):null - PubMed
  3. Cardiology. 2015;131(2):122-9 - PubMed
  4. J Am Coll Cardiol. 2007 Mar 20;49(11):1203-11 - PubMed
  5. J Am Coll Cardiol. 2005 Aug 2;46(3):470-6 - PubMed
  6. Am Heart J. 1993 Jun;125(6):1691-7 - PubMed
  7. J Mol Cell Cardiol. 2016 Jul;96:72-81 - PubMed
  8. Eur Heart J. 2014 Oct 14;35(39):2733-79 - PubMed
  9. N Engl J Med. 1982 Oct 14;307(16):997-9 - PubMed
  10. Europace. 2018 Nov 01;20(suppl_3):iii102-iii112 - PubMed
  11. J Cardiovasc Electrophysiol. 2006 May;17 Suppl 1:S79-S85 - PubMed
  12. Am J Physiol. 1987 Sep;253(3 Pt 2):H487-92 - PubMed
  13. Circ Res. 2009 Jan 30;104(2):201-9, 12p following 209 - PubMed
  14. J Mol Cell Cardiol. 2012 Jan;52(1):185-95 - PubMed
  15. J Am Soc Echocardiogr. 2011 Jan;24(1):75-82 - PubMed
  16. Eur J Clin Pharmacol. 1983;24(2):199-203 - PubMed
  17. Am J Cardiol. 1988 Nov 15;62(16):1085-8 - PubMed
  18. Circulation. 2013 Feb 5;127(5):575-84 - PubMed
  19. Am J Physiol. 1983 Jan;244(1):H80-8 - PubMed
  20. J Am Coll Cardiol. 2005 Apr 19;45(8):1251-8 - PubMed
  21. Basic Res Cardiol. 1986;81 Suppl 1:33-7 - PubMed
  22. Circ Res. 1975 Dec;37(6):844-54 - PubMed
  23. J Am Coll Cardiol. 2011 Nov 22;58(22):2313-21 - PubMed
  24. Circ Heart Fail. 2017 Mar;10(3): - PubMed
  25. Am J Physiol Cell Physiol. 2007 Sep;293(3):C1073-81 - PubMed
  26. Annu Rev Physiol. 2008;70:23-49 - PubMed
  27. J Am Coll Cardiol. 2011 Dec 13;58(25):2703-38 - PubMed
  28. Eur J Clin Pharmacol. 1988;35(5):467-74 - PubMed
  29. Science. 2016 Feb 5;351(6273):617-21 - PubMed
  30. Br J Pharmacol. 2018 Jul;175(13):2635-2652 - PubMed
  31. PLoS One. 2015 Jun 29;10(6):e0131179 - PubMed
  32. Circulation. 1982 Aug;66(2):447-53 - PubMed
  33. Biochem Biophys Res Commun. 2001 Feb 9;280(5):1243-50 - PubMed
  34. Clin Pharmacol Ther. 1985 Jul;38(1):37-44 - PubMed
  35. Eur J Pharmacol. 1981 Jan 5;69(1):11-24 - PubMed
  36. N Engl J Med. 2018 Aug 16;379(7):655-668 - PubMed
  37. Glob Cardiol Sci Pract. 2013 Nov 01;2013(3):222-42 - PubMed
  38. Circulation. 1998 Jan 6-13;97(1):41-7 - PubMed
  39. Naunyn Schmiedebergs Arch Pharmacol. 1986 Feb;332(2):184-95 - PubMed
  40. Prog Cardiovasc Dis. 2012 May-Jun;54(6):483-92 - PubMed
  41. Br J Pharmacol. 2012 Oct;167(3):493-504 - PubMed
  42. Circ Heart Fail. 2018 Jan;11(1):e004124 - PubMed
  43. Gen Pharmacol. 1989;20(1):105-9 - PubMed
  44. J Mol Cell Cardiol. 2013 Aug;61:2-10 - PubMed
  45. J Am Heart Assoc. 2017 May 26;6(6):null - PubMed
  46. J Cardiovasc Pharmacol. 1993 Feb;21(2):316-22 - PubMed
  47. J Vis Exp. 2014 Apr 21;(86):null - PubMed
  48. J Mol Cell Cardiol. 2010 Feb;48(2):293-301 - PubMed
  49. J Cardiovasc Pharmacol. 1995 Jun;25(6):953-60 - PubMed
  50. J Cardiovasc Pharmacol. 1996 Mar;27(3):355-61 - PubMed
  51. Circ Heart Fail. 2013 Jul;6(4):694-702 - PubMed
  52. Am J Cardiol. 2010 Nov 1;106(9):1307-12 - PubMed

Publication Types

Grant support