Advertisement

Failure of Inactivation of Hypertrophied Myocardium: A Cause of Impaired Left Ventricular Filling in Hypertrophic Cardiomyopathy and Aortic Stenosis

  • Walter J. Paulus
  • Stanislas U. Sys
  • Paul Nellens
  • Guy R. Heyndrickx
  • Eric Andries

Abstract

Impaired left ventricular filling has been observed in hypertrophic cardiomyopathy [1–5] and in pressure overload hypertrophy [1, 4, 6–12]. This impairment of left ventricular filling has been related to slow left ventricular pressure decay [13, 14], which prolongs isovolumic relaxation and impedes left ventricular inflow [15, 16]. A slow left ventricular pressure decay, persisting into the left ventricular filling phase can be explained by a failure of myocardial inactivation [17, 18], which causes incomplete myoplasmic calcium reuptake and favors persistent diastolic cross-bridge interaction and contractile tension generation. A failure of myocardial inactivation of the hypertrophied left ventricle could be induced by a shift of certain critical proteins involved in excitation-contraction coupling towards isomeric forms with slower enzyme kinetics and an altered calcium sensitivity [19, 20].

Keywords

Aortic Stenosis Left Ventricular Filling Left Ventricular Relaxation Ventricular Relaxation Hypertrophied Left Ventricle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Stewart S, Mason DT, Braunwald E (1968). Impaired rate of left ventricular filling in idiopathic hypertrophic subaortic stenosis and valvular aortic stenosis. Circulation 37: 8–14.PubMedGoogle Scholar
  2. 2.
    Sanderson JE, Gibson DG, Brown DJ, Goodwin JF (1977). Left ventricular filling in hypertrophic cardiomyopathy: An angiographic study. Br Heart J 39: 661–670.PubMedCrossRefGoogle Scholar
  3. 3.
    St John Sutton MG, Tajik AM, Gibson DG, et al (1978). Echocardiographic assessment of left ventricular filling and septal and posterior wall dynamics in idiopathic hypertrophic subaortic stenosis. Circulation 57: 512–520.PubMedGoogle Scholar
  4. 4.
    Hanrath P, Mathey DG, Siegert R, Bleifeld W (1980). Left ventricular relaxation and filling pattern in different forms of left ventricular hypertrophy: An echocardiographic study. Am J Cardiol 45: 15–23.PubMedCrossRefGoogle Scholar
  5. 5.
    Bonow RO, Dilsizian V, Rosing DR, et al (1985). Verapamil-induced improvement in left ventricular diastolic filling and increased exercise tolerance in patients with hypertrophic cardiomyopathy: Short-and long-term effects. Circulation 72: 853–864.PubMedCrossRefGoogle Scholar
  6. 6.
    Gibson DG, Traill TA, Hall RJC, Brown DJ (1979). Echocardiographic features of secondary left ventricular hypertrophy. Br Heart J 41: 54–59.PubMedCrossRefGoogle Scholar
  7. 7.
    Friedman MJ, Sahn DJ, Burris HA, et al (1979). Computerized echocardiographic analysis to detect abnormal systolic and diastolic left ventricular function in children with aortic stenosis. Am J Cardiol 44: 478–486.PubMedCrossRefGoogle Scholar
  8. 8.
    Fifer MA, Borow KM, Colan SD, Lorell BH (1985). Early diastolic left ventricular function in children and adults with aortic stenosis. 5: 1147–1154.Google Scholar
  9. 9.
    Fouad FM, Tarazi RC, Gallagher JH, et al (1980). Abnormal left ventricular relaxation in hypertensive patients. Clin. Sci. 59: 411S - 414S.PubMedGoogle Scholar
  10. 10.
    Inouye I, Massie B, Loge D, et al (1984). Abnormal left ventricular filling: An early finding in mild to moderate systemic hypertension. Am J Cardiol 53: 120–126.Google Scholar
  11. 11.
    Smith VE, Schulman P, Karimeddini MK, et al (1985). Rapid ventricular filling in left ventricular hypertrophy: II, Pathologic hypertrophy. J Am Coll Cardiol 5: 869–874.PubMedCrossRefGoogle Scholar
  12. 12.
    Murakami T, Hess OM, Gage JE, et al (1986). Diastolic filling dynamics in patients with aortic stenosis. Circulation 6: 1162–1174.CrossRefGoogle Scholar
  13. 13.
    Lorell BH, Paulus WJ, Grossman W, et al (1982). Modification of abnormal left ventricular diastolic properties by nifedipine in patients with hypertrophic cardiomyopathy. Circulation 65: 499–507.PubMedCrossRefGoogle Scholar
  14. 14.
    Murgo JP, Craig WE (1980). Relaxation abnormalities in hypertrophic cardiomyopathy. Circulation 62 (suppl III): 316 (abstract).Google Scholar
  15. 15.
    Goodwin JF (1980). Hypertrophic cardiomyopathy: A disease in search of its own identity. Am J Cardiol 45: 177–180.PubMedCrossRefGoogle Scholar
  16. 16.
    Betocchi S, Bonow RO, Bacharach SL, et al (1986). Isovolumic relaxation period in hypertrophic cardiomyopathy: assessment by radionuclide angiography. J Am Coll Cardiol 7: 74–81, 1986.Google Scholar
  17. 17.
    Paulus WJ, Lorell BH, Craig WE, et al (1983). Comparison of the effects of nitroprusside and nifedipine on diastolic properties in patients with hypertrophic cardiomyopathy: Altered left ventricular loading or improved muscle inactivation? J Am Coll Cardiol 2: 879–886.PubMedCrossRefGoogle Scholar
  18. 18.
    Paulus WJ, Nellens P, Heyndrickx GR, Andries E (1986). Effects of long-term treatment with amiodarone on exercise hemodyna mics and left ventricular relaxation in patients with hypertrophic cardiomyopathy. Circulation 74: 544–554.PubMedCrossRefGoogle Scholar
  19. 19.
    Gwathmey JK, Morgan JP (1985). Altered calcium handling in experimental pressure over load hypertrophy in the ferret. Circ Res 57: 836–843.PubMedGoogle Scholar
  20. 20.
    Entman ML, Van Winkle WB, McMillin Wood JB (1985). The biochemistry of excitation-contraction coupling: Implications with regard to pump failure. In Levine HJ, Gaasch WH (eds): The Ventricle: Basic and Clinical Aspects. Boston: Martinus Nijhoff, pp 63–77.Google Scholar
  21. 21.
    Lossnitzer K, Janke J, Hein B, et al (1975). Disturbed myocardial calcium metabolism: a possible pathogenetic factor in the hereditary cardiomyopathy of the Syrian hamster. In Fleckenstein A, Rona G (eds): Recent Advances in Studies on Cardiac Structure and Function. Baltimore: University Park Press, pp 207–217.Google Scholar
  22. 22.
    Lorell BH, Barry WH (1984). Effects of verapamil on contraction and relaxation of cultured chick embryo ventricular cells during calcium overload J Am Coll Cardiol 3: 341–348.Google Scholar
  23. 23.
    Rouleau JL, Chuck LHS, Hollosi G, et al (1982). Verapamil preserves myocardial contractility in the hereditary cardiomyopathy of the Syrian hamster. Circ Res 50: 405–412.PubMedGoogle Scholar
  24. 24.
    Johnson EA (1979). Force-interval relationship of cardiac muscle. In Berne RM, Sperelakis N, Geiger SR (eds): Handbook of Physiology II. The Cardiovascular System. Bethesda, MD: American Physiological Society, 475–496.Google Scholar
  25. 25.
    Blaustein AS, Gaasch WH, Adam D, Levine HJ (1981). Myocardial relaxation. V. Postextrasystolic contraction-relaxation in the intact dog heart. Circulation 64: 345–351.Google Scholar
  26. 26.
    Carroll JD, Widmer R, Hess OM, et al (1983). Left ventricular isovolumic pressure decay and diastolic mechanics after postextrasystolic potentiation and during exercise. Am J Cardiol 51: 583–590.PubMedCrossRefGoogle Scholar
  27. 27.
    Nakamura Y, Konishi T, Nonogi H, et al (1986). Myocardial relaxation in atrial fibrillation J Am Coll Cardiol 7: 68–73.Google Scholar
  28. 28.
    Eichhorn P, Grimm J Koch R, et al (1982). Left ventricular relaxation in patients with left ventricular hypertrophy secondary to aortic valve disease. Circulation 65: 1395–1404.PubMedCrossRefGoogle Scholar
  29. 29.
    Hess O, Job JG, Kraft A, Krayenbuehl HP (1984). Is left ventricular relaxation delayed in patients with aortic stenosis? Circulation 70 (suppl II): 303 (abstract)CrossRefGoogle Scholar
  30. 30.
    Takenaka K, Dabestani A, Gardin JM, et al (1986). Left ventricular filling in hypertrophic cardiomyopathy: A pulsed doppler echocardiographic study. J Am Coll Cardiol 7: 1263–1271.PubMedCrossRefGoogle Scholar
  31. 31.
    Spirito P, Maron BJ, Bonow RO (1986). Noninvasive assessment of left ventricular diastolic function: Comparative analysis of doppler echo cardiographic and radionuclide angiographic techniques. J Am Coll Cardiol. 7: 518–526.PubMedCrossRefGoogle Scholar
  32. 32.
    Weiss JL, Frederiksen JW, Weisfeldt ML (1976). Hemodynamic determinants of the time course of fall in canine left ventricular pressure. J Clin Invest 58: 751–760.PubMedCrossRefGoogle Scholar
  33. 33.
    Gaasch WH, Blaustein AS, Andrias CW, et al (1980). Myocardial relaxation. II. Hemodynamic determinants of the rate of left ventricular isovolumic pressure decline. Am J Physiol 239: H1 - H6.PubMedGoogle Scholar
  34. 34.
    Raff GL, Glantz SA (1981). Volume loading slows left ventricular isovolumic relaxation rate: Evidence of load-dependent relaxation in the intact dog heart. Circ Res 48: 813–824.Google Scholar
  35. 35.
    Mirsky I (1984). Assessment of diastolic function: suggested methods and future considerations. Circulation 69: 836–841.PubMedCrossRefGoogle Scholar
  36. 36.
    Serizawa, T (1978). An experimental study of left ventricular isovolumetric relaxation period: On the fitting of left ventricular pressure fall to exponential function: Tokyo J Med Sci 85: 295–308.Google Scholar
  37. 37.
    Pagani M, Pizzinelli P, Gussomi M, et al (1983). Diastolic abnormalities of hypertrophic cardiomyopathy reproduced by asynchrony of the left ventricle in conscious dogs J Am Coll Cardiol (abstract).Google Scholar
  38. 38.
    Rousseau MF, Veriter C, Detry JR, et al (1980). Impaired early left ventricular relaxation in coronary artery disease: effects of intracoronary nifedipine. Circulation 62: 764–772.PubMedGoogle Scholar
  39. 39.
    Craig WE, Murgo JB (1980). Evaluation of isovolumic relaxation in normal man during rest, exercise and isoproterenol infusion. Circulation 62 (suppl III): 192 (abstract).Google Scholar
  40. 40.
    Martin G, Gimeno JV, Cosin J, Guillem MI (1984). Time constant of isovolumic pressure fall: New numerical approaches and significance Am J Physiol 247: H283 - H294.Google Scholar
  41. 41.
    Gibson DG, Doran JH, Traill TA, and Brown DJ (1978). Regional abnormalities of left ventricular wall movement during isovolumic relaxation in patients with ischemic heart disease. Eur J Cardiol 7 (suppl): 251–264.PubMedGoogle Scholar
  42. 42.
    Parmley WW, Sonnenblick EH (1967). Series elasticity of heart muscle: Its relation to contractile element velocity and proposed muscle models. Circ Res 20: 112–123.PubMedGoogle Scholar
  43. 43.
    Winegrad S, Weisberg A, MacClellan G (1980). Are restoring forces important to relaxation? Eur Heart J 1 (suppl A): 59–65.Google Scholar
  44. 44.
    Paulus WJ, Serizawa T, Grossman W (1982). Altered left ventricular diastolic properties during pacing-induced ischemia in dogs with coronary stenoses: Potentiation by caffeine. Circ Res 50: 218–227.Google Scholar
  45. 45.
    Grossman W, Barry WH (1980). Diastolic pressure-volume relations in the diseased heart. Fed Proc 39: 18–25.Google Scholar
  46. 46.
    Pouleur H, Karliner JS, LeWinter MM, Covell JW (1979). Diastolic viscous properties of the intact canine left ventricle. Circ Res 45: 410–419.PubMedGoogle Scholar
  47. 47.
    Hess OM, Schneider J, Koch R, et al (1981). Diastolic function and myocardial structure in patients with myocardial hypertrophy. Circulation 63: 360–371.PubMedCrossRefGoogle Scholar
  48. 48.
    Paulus WJ, Claes VA, Brutsaert DL (1976). Physiological loading of isolated mammalian cardiac muscle. Circ Res 39: 42–53.PubMedGoogle Scholar
  49. 49.
    O’Rourke MF (1982). Arterial Function in Health and Disease Edinburgh: Churchill Livingstone.Google Scholar
  50. 50.
    Paulus WJ, Claes VA, Brutsaert DL (1980). End-systolic pressure-volume relation estimated from physiologically loaded cat papillary muscle contractions. Circ Res 47: 20–26.PubMedGoogle Scholar
  51. 51.
    Wiggle ED, Sasson Z, Henderson MA, et al (1985). Hypertrophic cardiomyopathy: The importance of the site and the extent of hypertrophy. A review. Prog Cardiovasc Dis 28: 1–83.CrossRefGoogle Scholar
  52. 52.
    Maron BJ, Gottdiener JS, Epstein SE (1981). Patterns and significance of distribution of left ventricular hypertrophy in hypertrophic cardiomyopathy. Am J Cardiol 48: 418–428.PubMedCrossRefGoogle Scholar
  53. 53.
    Shapiro LM, MacKenna WJ (1983). Distribution of left ventricular hypertrophy in hypertrophic cardiomyopathy: A two-dimensional echocardiographic study. J Am Coll Cardiol 2: 437–444.PubMedCrossRefGoogle Scholar
  54. 54.
    Housmans PR, Lee NKM, Blinks JR (1983). Active shortening retards the decline of the intracellular calcium transient in mammalian heart muscle. Science 221: 159–161.PubMedCrossRefGoogle Scholar
  55. 55.
    Hess OM, Surber EP, Ritter M Krayenbuehl HP (1984). Pulsus alternans: Its influence on systolic and diastolic function in aortic valve disease. J Am Coll Cardiol 4: 1–47.Google Scholar
  56. 56.
    Fabiato A (1983). Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. Am J Physiol 245: C1 - C14.PubMedGoogle Scholar
  57. 57.
    Levitsky DO, Benevolensky DS (1986). Effects of changing Ca’ to H+ ratio on Ca’ uptake by sarcoplasmic reticulum. Am J Physiol 250: H360 - H365.PubMedGoogle Scholar
  58. 58.
    Brutsaert DL, Housmans PR, Goethals MA (1980). Dual control of relaxation: its role in the ventricular function in the mammalian heart. Circ Res 47: 637–652.PubMedGoogle Scholar
  59. 59.
    Diver DJ, Royal HD, Aroesty JM, et al (19). Load independence of abnormal diastolic function in patients with aortic stenosis. J Am Coll Cardiol (in press).Google Scholar
  60. 60.
    Brecher GA (1958). Critical review of recent work on ventricular diastolic suction. Circ Res 6: 554–566.PubMedGoogle Scholar
  61. 61.
    Sabbah HN, Stein PD (1981). Pressure-diameter relations during early diastole in dogs: incompatibility with the concept of passive left ventricular filling. Circ Res 48: 357–364.PubMedGoogle Scholar
  62. 62.
    Bahler RC, Martin P (1985). Effects of loading conditions and inotropic state on rapid filling phase of left ventricle. Am J Physiol 248: H523 - H533.PubMedGoogle Scholar
  63. 63.
    Ishida Y, Meisner JS, Tsujioka K, et al (1986). Left ventricular filling dynamics: influence of left ventricular relaxation and left atrial pressure. Circulation 74: 187–196.PubMedCrossRefGoogle Scholar
  64. 64.
    Carroll JD, Blaustein AS, Donaldson JT, et al (1981). Verapamil uncouples contraction-relaxation in the canine left ventricle. Circulation 64 (suppl IV): 211 (abstract).Google Scholar

Copyright information

© Martinus Nijhoff Publishing 1987

Authors and Affiliations

  • Walter J. Paulus
  • Stanislas U. Sys
  • Paul Nellens
  • Guy R. Heyndrickx
  • Eric Andries

There are no affiliations available

Personalised recommendations