Abstract
Background: Cibenzoline, a class la antiarrhythmic drug, can be used to relieve left ventricular (LV) outflow obstruction in hypertrophic obstructive cardiomyopathy (HOCM). However, the mechanism of this agent in HOCM has been controversial.
Hypothesis: This study was designed to investigate the effect of cibenzoline on regional LV function and the acoustic properties in HOCM using ultrasonic integrated backscatter.
Methods: Ten patients with HOCM and 16 healthy volunteers were examined. In patients with HOCM, wall thickening (%WT) and the magnitude of cyclic variation of integrated backscatter (mag‐CVIBS) in the interventricular septum (IVS) and LV posterior wall were measured before and after oral administration of cibenzoline. To assess asynchrony of contractile elements, the phase difference between CVIBS and%WT were measured from the LV posterior wall. Pressure gradients at the LV outflow tract were estimated using continuous‐wave Doppler echocardiography.
Results: Although%WT decreased significantly in the LV posterior wall, %WT and mag‐CVIBS remained unchanged in the IVS. The phase difference in the LV posterior wall was significantly greater in patients with HOCM than in healthy volunteers (HOCM:healthy volunteers, 1.57 ± 0.23:1.00 ± 0.03, p < 0.001) at baseline. After administration of cibenzoline, the phase difference shifted to normal value (from 1.57 ± 0.23 to 1.28 ± 0.27, p = 0.0382), and pressure gradients at the LV outflow tract decreased (from 109 ± 55 to 58 ± 48 mmHg, p = 0.0063). Changes in pressure gradients at the LV outflow tract and the phase difference were closely related.
Conclusions: Regional function and the acoustic properties of myocardium in HOCM were altered by cibenzoline in the LV posterior wall but remained unchanged in the IVS. The normalization of the phase difference in the LV posterior wall was closely related to the decrease in pressure gradients at the LV outflow tract. These findings suggest that negative inotropic action and the improvement of asynchrony in the LV posterior wall rather than in the IVS may contribute to the reduction of pressure gradients at the LV outflow tract in HOCM.
Keywords: cibenzoline, hypertrophic obstructive cardiomyopathy, left ventricular function, acoustic properties, ultrasonic integrated backscatter, phase difference, asynchrony
Full Text
The Full Text of this article is available as a PDF (743.9 KB).
References
- 1. Hamada M, Shigematsu Y, Dceda S, Hara Y, Okayama H, Ochi T, Hiwada K: Class Ia antiarrhythmic drug cibenzoline: A new approach to the medical treatment of hypertrophic obstructive cardiomyopathy. Circulation 1997; 96: 1520–1524 [DOI] [PubMed] [Google Scholar]
- 2. Masse C, Cazes M, Sassine A: Effects of cibenzoline, a novel antiarrhythmic drug, on action potential and transmembrane currents in frog atrial muscle. Arch Int Pharmacodyn Ther 1984; 269 (2): 219–235 [PubMed] [Google Scholar]
- 3. Canal M, Flouvat B, Tremblay D, Dufour A: Pharmacokinetics in man of a new antiarrhythmic drug, cibenzoline. Eur J Clin Pharmacol 1983; 24 (4): 509–515 [DOI] [PubMed] [Google Scholar]
- 4. Millar JS, Vaughan Williams EM: Pharmacological mapping of regional effects in the rabbit heart of some new antiarrhythmic drugs. Br J Pharmacol 1983; 79: 701–709 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Ohtsuka T, Hamada M, Hara Y, Kuwahara T, Kodama K, Shigematsu Y, Iwata T, Hiwada K: An early systolic sound associated with mid ventricular obstruction in a patient with hypertrophic cardiomyopathy. Jpn Circ J 1998; 62: 385–388 [DOI] [PubMed] [Google Scholar]
- 6. Pollick C: Muscular subaortic stenosis: Hemodynamic and clinical improvement after disopyramide. N Engl J Med 1982; 307: 997–999 [DOI] [PubMed] [Google Scholar]
- 7. Pollick C, Kimball B, Henderson M, Wigle ED: Disopyramide in hypertrophic cardiomyopathy I. Hemodynamic assessment after intravenous administration. Am J Cardiol 1988; 62: 1248–1251 [DOI] [PubMed] [Google Scholar]
- 8. Pollick C: Disopyramide in hypertrophic cardiomyopathy II. Noninvasive assessment after oral administration. Am J Cardiol 1988; 62: 1252–1255 [DOI] [PubMed] [Google Scholar]
- 9. Sherrid M, Delia E, Dwyer E: Oral disopyramide therapy for obstructive hypertrophic cardiomyopathy. Am J Cardiol 1988; 62: 1085–1088 [DOI] [PubMed] [Google Scholar]
- 10. Sumimoto T, Hamada M, Ohtani T, Suzuki M, Abe M, Matsuoka H, Fujikawa Y, Sekiya M, Hiwada K: Effect of disopyramide on left ventricular diastole function in patients with hypertrophic cardiomyopathy: Comparison with diltiazem. Cardiovasc Drug Ther 1992; 6: 425–428 [DOI] [PubMed] [Google Scholar]
- 11. Kimball BP, Bui S, Wigle ED: Acute dose‐response effects of intravenous disopyramide in hypertrophic cardiomyopathy. Am Heart J 1993; 125: 1691–1697 [DOI] [PubMed] [Google Scholar]
- 12. Cokkinos DV, Salpeas D, Ioannou NE, Christoulas S: Combination of disopyramide and propranolol in hypertrophic cardiomyopathy. Can J Cardiol 1989; 5: 33–36 [PubMed] [Google Scholar]
- 13. Minbs JW, O'Donnel M, Bauwens D, Miller JG, Sobel BE: The dependence of ultrasonic attenuation and backscatter on collagen content in dog and rabbit hearts. Circ Res 1980; 47: 48–58 [DOI] [PubMed] [Google Scholar]
- 14. O'Donnel M, Minbs JW, Miller JG: Relationship between collagen and ultrasonic backscatter in myocardial tissue. JAcoust Soc Am 1981; 69: 580–588 [DOI] [PubMed] [Google Scholar]
- 15. Madaras EL, Barzilai B, Perez JE, Sobel BE, Miller JG: Changes in myocardial backscatter throughout the cardiac cycle. Ultrason Imag 1983; 5: 229–239 [DOI] [PubMed] [Google Scholar]
- 16. Mottley JG, Glueck RM, Perez JE, Sobel BE, Miller JG: Regional differences in the cyclic variation of myocardial backscatter that parallel regional difference in contractile performance. J Acoust Soc Am 1984; 76: 1617–1623 [DOI] [PubMed] [Google Scholar]
- 17. Barzilai B, Madaras EL, Sobel BE, Miller JG, Perez JE: Effects of myocardial contraction on ultrasonic backscatter before and after ischemia. Am J Physiol 1984; 247: H478–483 [DOI] [PubMed] [Google Scholar]
- 18. Miller JG, Perez JE, Sobel BE: Ultrasonic characterization of myocardium. Prog Cardiovasc Dis 1985; 28: 85–110 [DOI] [PubMed] [Google Scholar]
- 19. Nozaki S, DeMaria AN, Helmer GA, Hammond HK: Detection of regional left ventricular dysfunction in early pacing‐induced heart failure using ultrasonic integrated backscatter. Circulation 1995; 92: 2675–2682 [DOI] [PubMed] [Google Scholar]
- 20. Wickline SA, Thomas U III, Miller JG, Sobel BE, Perez JE: The dependence of myocardial ultrasonic integrated backscatter on contractile performance. Circulation 1985; 72: 183–192 [DOI] [PubMed] [Google Scholar]
- 21. Wickline SA, Thomas LJ III, Miller JG, Sobel BE, Perez JE: Sensitive detection of the effects of reperfusion on myocardium by ultrasonic tissue characterization with increased integrated back‐scatter. Circulation 1986; 74: 389–400 [DOI] [PubMed] [Google Scholar]
- 22. O'Brien PD, O'Brien WD Jr, Rhyne TL, Warltier DC, Sagar KB: Relation of ultrasonic backscatter and acoustic propagation properties to myofibrillar length and myocardial thickness. Circulation 1995; 91: 171–175 [DOI] [PubMed] [Google Scholar]
- 23. Report of the WHO/ISFC Task Force on the Definition and Classification of Cardiomyopathies. Br Heart J 1980; 44: 672–673 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Sahn DJ, DeMaria A, Kisslo J, Weyman A: Recommendations regarding quantification in M‐mode echocardiography: Results of a survey of echocardiographic measurements. Circulation 1978; 58: 1072–1083 [DOI] [PubMed] [Google Scholar]
- 25. Wickline SA, Thomas LJ III, Miller JG, Sobel BE, Perez JE: A relationship between ultrasonic integrated backscatter and myocardial contractile function. J Clin Invest 1985; 76: 2151–2160 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26. Rijsteborg H, Mastik F, Lancée CT, van der Steen AF, Verdouw PD, Roelandt J, Bom N: Ultrasonic integrated backscatter and myocardial wall thickness in animal experiments. Ultrasound Med Biol 1990; 16: 29–36 [DOI] [PubMed] [Google Scholar]
- 27. Takiuchi S, Ito H, Iwakura K, Taniyama Y, Nishikawa N, Masuyama T, Hori M, Higashino Y, Fujii K, Minamino T: Ultrasonic tissue characterization predicts myocardial viability in early stage of reperfused acute myocardial infarction. Circulation 1998; 97: 356–362 [DOI] [PubMed] [Google Scholar]
- 28. Matsubara H, Nakatani S, Nagata S, Ishikura F, Katagiri Y, Ohe T, Miyatake K: Salutary effect of disopyramide on left ventricular diastolic function in hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol 1995; 26: 768–775 [DOI] [PubMed] [Google Scholar]
- 29. Maron BJ, Roberts WC: Quantitative analysis of cardiac muscle cell disorganization in the ventricular septum of patients with hypertrophic cardiomyopathy. Circulation 1979; 59: 689–706 [DOI] [PubMed] [Google Scholar]
- 30. Maron BJ, Anan TJ, Roberts WC: Quantitative analysis of the distribution of cardiac muscle cell disorganization in the left ventricular wall of patients with hypertrophic cardiomyopathy. Circulation 1981; 63: 882–894 [DOI] [PubMed] [Google Scholar]