Skip to main content
SpringerLink
Log in

Diastolic Dysfunction as a Cause of Exercise Intolerance

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

Tachycardia accompanying exercise shortens the duration of diastole, reducing the time available for the left ventricular (LV) filling. Thus, the LV must fill more rapidly for the stroke volume to increase (or even be maintained) during exercise. Normally, this is accomplished without requiring an excessive increase in left atrial (LA) pressure by an acceleration of LV relaxation and a fall in LV early diastolic pressure during exercise. This response is lost following the development of heart failure due to systolic dysfunction, both in experimental animals and in patients. In fact, in such situations, LV relaxation slows and LV early diastolic pressure increases due to exercise. Thus, any diastolic dysfunction present at rest in CHF during systolic dysfunction is exacerbated during exercise. Similarly, patients with primary diastolic dysfunction heart failure with preserved systolic function may not be able to augment LV filling rates without an abnormal increase in LA pressure. Thus, diastolic dysfunction may contribute to exercise intolerance, both in systolic dysfunction and primary diastolic dysfunction. Acute studies suggest that treatment with angiotensin II receptor blockers or verapamil may improve exercise tolerance in some patients with primary diastolic dysfunction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Packer M. Abnormalities of diastolic function as a potential cause of exercise intolerance in chronic heart failure. Circulation 1990;81:11178–11186.

    Google Scholar 

  2. Wasserman K. Reduced aerobic enzyme activity in skeletal muscles of patients with heart failure: A primary defect or a result of limited cardiac output? Circulation 1991;84:1868–1870.

    Google Scholar 

  3. Pouleur H, Hanet C, Rousseau MF, Van Eyll C. Relation of diastolic function and exercise capacity in ischemic left ventricular dysfunction. Role of beta-agonists and beta-antagonists. Circulation 1990;82:189–196.

    Google Scholar 

  4. Kitzman DW, Higginbotham MB, Cobb FR, Sheikh KH, Sullivan MJ. Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the Frank-Starling mechanism. J Am Coll Cardiol 1991;17:1065–1072.

    Google Scholar 

  5. Ishida Y, Meisner JS, Tjujioka K, et al. Left ventricular filling dynamics: influence of left ventricular relaxation and left atrial pressure. Circulation 1986;74:187–196.

    Google Scholar 

  6. Cheng CP, Freeman GL, Santamore WP, Constantinescu MS, Little WC. Effect of loading conditions, contractile state, and heart rate on early diastolic left ventricular filling in conscious dogs. Circ Res 1990;66:814–823.

    Google Scholar 

  7. Choong CY, Abascal VM, Thomas JD, Guerrero JL, McGlew S, Weyman AE. Combined influence of ventricular loading and relaxation on the transmitral flow velocity profile in dogs measured by Doppler echocardiology. Circulation 1988;78:672–683.

    Google Scholar 

  8. Courtois M, Vered Z, Barzilai B, Ricciotti NA, Perez JE, Ludbrook PA. The transmitral pressure-flow velocity relation: effect of abrupt preload reduction. Circulation 1988;78:1459–1468.

    Google Scholar 

  9. Courtois M, Kovacs SJ, Jr., Ludbrook PA. Transmitral pressure-flow velocity relation: importance of regional pressure gradients in the left ventricle during diastole. Circulation 1988;78:661–671.

    Google Scholar 

  10. Thomas JD, Weyman AE. Echocardiographic Doppler evaluation of left ventricular diastolic function. Physics and physiology. Circulation 1991;84:977–990.

    Google Scholar 

  11. Thomas JD, Weyman AE. Numerical modeling of ventricular filling. Ann Biomed Eng 1992;20:19–39.

    Google Scholar 

  12. Thomas JD, Flachskampf FA, Chen C, et al. Isovolumic relaxation time varies predictably with its time constant and aortic and left atrial pressures: implications for the noninvasive evaluation of ventricular relaxation. Am Heart J 1992;124:1305–1313.

    Google Scholar 

  13. Little WC, Cheng CP. Modulation of diastolic dysfunction in the intact heart. In: Lorell BM, Grossman W, eds. Kluwer Academic Publishers; 1994:107-176

  14. Vatner SF, Pagani M. Cardiovascular adjustments to exercise: hemodynamics and mechanisms. Prog Card Dis 1976;19:91–108.

    Google Scholar 

  15. Puliner LR, Dehmer GJ, Lewis SE, Parkey SW, Blomquist CG, Willerson JT. Left ventricular performance in normal subjects: a comparison of the responses to exercise in the upright and supine positions. Circulation 1980;62:528–534.

    Google Scholar 

  16. Higginbotham MB, Morris KG, Williams RS, McHale PA, Colemen RE, Cobb FR. Regulation of stroke volume during submaximal and maximal upright exercise in normal man. Circ Res 1986;58:281–291.

    Google Scholar 

  17. Nonogi H, Hess OM, Ritter M, Krayenbuehl HP. Diastolic properties of the normal left ventricle during supine exercise. Br Heart J 1988;60:30–38.

    Google Scholar 

  18. Rassi A, Jr., Crawford MH, Richards KL, Miller JF. Differing mechanisms of exercise flow augmentation at the mitral and aortic valves. Circulation 1988;77:543–551.

    Google Scholar 

  19. Mitchell GD, Brunken RC, Schwaiger M, Donohue BC, Krivokapich J, Child JS. Assessment of mitral flow velocity with exercise by an index of stress-induced left ventricular ischemia in coronary artery disease. Am J Cardiol 1988;61:536–540.

    Google Scholar 

  20. Cheng CP, Igarashi Y, Little WC. Mechanism of augmented rate of left ventricular filling during exercise. Circ Res 1992;70:9–19.

    Google Scholar 

  21. Miyazaki S, Guth BD, Miura T, Indolfi C, Schulz R, Ross J, Jr. Changes of left ventricular diastolic function in exercising dogs without and with ischemia. Circulation 1990;81:1058–1070.

    Google Scholar 

  22. Brutsaert DL, Rademakers FE, Sys SU. Triple control of relaxation: implications in cardiac disease. Circulation 1984;69:190–196.

    Google Scholar 

  23. Nikolic S, Yellin EL, Tamura K, et al. Passive properties of canine left ventricle: diastolic stiffness and restoring forces. Circ Res 1988;62:1210–1222.

    Google Scholar 

  24. Gilbert JC, Glantz SA. Determinants of left ventricular filling and of the diastolic pressure-volume relations. Circ Res 1989;64:827–852.

    Google Scholar 

  25. Udelson JE, Bacharach SL, Cannon RO, III, Bonow RO. Minimum left ventricular pressure during beta-adrenergic stimulation in human subjects. Evidence for elastic recoil and diastolic `suction' in the normal heart. Circulation 1990;82:1174–1182.

    Google Scholar 

  26. Gibbons Kroeker CA, Ter Keurs HE, Knudtson ML, Tyberg JV, Beyar R. An optical device to measure the dynamics of apex rotation of the left ventricle. Am J Physiol 1993;265:H1444–H1449

    Google Scholar 

  27. Aroesty JM, McKay RG, Heller GV, Royal HD, Als AV, Grossman W. Simultaneous assessment of left ventricular systolic and diastolic dysfunction during pacing-induced ischemia. Circulation 1985;71:889–900.

    Google Scholar 

  28. Freeman GL, Little WC, O'Rourke RA. Influence of heart rate on the left ventricular performance in conscious dogs. Circ Res 1987;61:455–464.

    Google Scholar 

  29. Lew WYW. Evaluation of left ventricular diastolic function. Circulation 1989;79:1393–1397.

    Google Scholar 

  30. Miura T, Miyazaki S, Guth BD, Kambayashi M, Ross J, Jr. Influence of the force-frequency relation on left ventricular function during exercise in conscious dogs. Circulation 1992;86:563–571.

    Google Scholar 

  31. Cheng CP, Noda T, Nozawa T, Little WC. Effect of heart failure on the mechanism of exercise-induced augmentation of mitral valve flow. Circ Res 1993;72:795–806.

    Google Scholar 

  32. Sato H, Hori M, Ozaki H, et al. Exercise-induced upward shift of diastolic left ventricular pressure-volume relation in patients with dilated cardiomyopathy. Effects of beta-adrenoceptor blockade. Circulation 1993;88:2215–2223.

    Google Scholar 

  33. Zampaglione B, Pascale C, Marchisio M, Cavallo-Perin P. Hypertensive urgencies and emergencies: prevalence and clinical presentation. Hypertension 1996;27:144–147.

    Google Scholar 

  34. Stratton JR, Levy WC, Cerqueira MD, Schwartz RS, Abrass IB. Cardiovascular responses to exercise: effects of aging and exercise training in healthy men. Circulation 1994;89:1648–1655.

    Google Scholar 

  35. Fleg JL, O'Connor F, Gerstenblith G, et al. Impact of age on the cardiovascular response to dynamic upright exercise in healthy men and women. J Appl Physiol 1995;78:890–900.

    Google Scholar 

  36. Fagard R, Staessen J, Thijs L, Amery A. Prognostic significance of exercise versus resting blood pressure in hypertensive men. Hypertension 1991;17:574–578.

    Google Scholar 

  37. Aldigier JC, Huang H, Dalmay F, et al. Angiotensin-converting enzyme inhibition does not suppress plasma angiotensin II increase during exercise in humans. J Cardiovasc Pharmacol 1993;21:289–295.

    Google Scholar 

  38. Cheng CP, Suzuki M, Ohte N, Ohno M, Wang ZM, Little WC. Altered ventricular and myocyte response to angiotensin II in pacing-induced heart failure. Circ Res 1996;78:880–892.

    Google Scholar 

  39. Haber HL, Powers ER, Gimple LW, et al. Intracoronary angiotensin-converting enzyme inhibition improves diastolic function in patients with hypertensive left ventricular hypertrophy. Circulation 1994;89:2616–2625.

    Google Scholar 

  40. Friedrich SP, Lorell BH, Rousseau MF, et al. Intracardiac angiotensin-converting enzyme inhibition improves diastolic function in patients with left ventricular hypertrophy due to aortic stenosis. Circulation 1994;90:2761–2671.

    Google Scholar 

  41. Warner JG, Jr., Metzger DC, Kitzman DW, Wesley DJ, Little WC. Losartan improves exercise tolerance in patients with diastolic dysfunction and a hypertensive response to exercise. JACC 1999;33:1567–1572.

    Google Scholar 

  42. Ohno M, Cheng CP, Little WC. Mechanism of altered patterns of left ventricular filling during the development of congestive heart failure. Circulation 1994;89:2241–2250.

    Google Scholar 

  43. Rector TS, Tschumperlin LK, Kubo SH, et al. Use of the Living With Heart Failure questionnaire to ascertain patients' perspectives on improvement in quality of life versus risk of drug-induced death. Journal of Cardiac Failure 1995;1:201–206.

    Google Scholar 

  44. Little WC, Braunwald E. Assessment of cardiac function. In: Braunwald E, ed. Heart Disease. 5 ed. Philadelphia, PA: W. B. Saunders Co.; 1997:421–444.

    Google Scholar 

  45. Setaro JF, Zaret BL, Schulman DS, Black HR, Soufer R. Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic filling and normal left ventricular systolic performance. Am J Cardiol 1990;66:981–986.

    Google Scholar 

  46. Chen CH, Nakayama M, Talbot M, et al. Verapamil acutely reduces ventricular-vascular stiffening and improves aerobic exercise performance in elderly individuals. JACC 1999;33:1602–1609.

    Google Scholar 

  47. Bonow RO, Dilsizian V, Rosing DR, Maron BJ, Bacharach SL, Green MV. Verapamil-induced improvement in left ventricular diastolic filling and increased exercise tolerance in patients with hypertrophic cardiomyopathy: short-and long-term effects. Circulation 1985;72:853–864.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cardiology Section, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1045

    William C. Little,  Dalane W. Kitzman &  Che-Ping Cheng

Authors
  1. William C. Little
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dalane W. Kitzman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Che-Ping Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Little, W.C., Kitzman, D.W. & Cheng, CP. Diastolic Dysfunction as a Cause of Exercise Intolerance. Heart Fail Rev 5, 301–306 (2000). https://doi.org/10.1023/A:1026503028065

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026503028065

Search

Navigation