Congestive heart failure: Systolic and diastolic function

Congestive

Heart Failure:

Systolic

William C. Little, MD, and Robert There is increasing recognition that disorders of both left ventricular systolic and diastolic function can result in congestive heart failure. As such, consideration of both the filling and emptying characteristics of the left heart is needed to evaluate the hemodynamic abnormalities present in this syndrome. Consideration of the systolic (emptying) and diastolic (filling) pumping characteristics of the left heart also provides a conceptual basis to classify and understand the pathophysiology of congestive heart failure. In this context, systolic dysfunction can be defined as impaired emptying of the LV, apparent as a decreased (~50%) effective ejection fraction (forward stroke volume divided by end-diastolic volume). Systolic dysfunction may result from impaired myocardial contractile function, increased left ventricular afterload, and/or structural abnormalities of the left heart. Diastolic dysfunction can be defined as a condition in which filling of the LV sufficient to produce an adequate cardiac

F

AILURE OF THE cardiac output to meet the needs of the body activates several compensatory mechanisms, resulting in an elevation of the intravascular volume and venous tone.’ This tends to restore the cardiac output to normal while pulmonary venous prcssurc rises. Thus, most patients with congestive heart failure have a cardiac output that is adequate to meet the needs of the body at rest, but have elevation of the pulmonary venous pressure producing pulmonary congestion. Exercise intolerance in heart failure patients may be due to elevated pulmonary venous pressure and not an inadequate cardiac output.? Thus, the syndrome of circulatory dysfunction, due to impairment of left heart function, is termed congestive heart failure. In addition, congestive heart failure may be present in patients with diastolic dysfunction who do not have impaired systolic function7 Analysis of the left heart as a pump is a useful method to understand how the heart receives and ejects the blood necessary to maintain the normal circulation. The input force for the left ventricle (LV) is the pulmonary venous (or mean left atrial) pressure. The output of the left heart is the cardiac output (Fig 1). Using this approach, the pump performance of the LV can also be considered in terms of its filling (diastolic function) and its emptying (systolic function). Consideration of the systolic and diastolic pumping characteristics of the left heart provides a conceptual basis to classily and understand the pathophysiology of congestive heart failure.’ Systolic Dysfunction

Congestive heart failure can be divided into disorders of systolic and diastolic LV dysfunction (Table 1). Systolic left From The Bowman Gray School of Medicine, Departmerlt of Internal Medicine, Winston-Salem, NC. Address reprint requests to William C. Little, MD, Professor of Internal Medicine, Chiej Cardiology Section, The Bowman Gray School of Medicine. Medical Center Blvd, Winston-Salem, NC 27157. 1045. Copyright “_” 1993 by W.B. Saunders Company 10.53-0770193/0704-0202$03.0010 2

and Diastolic J. Applegate,

Function

MD

output requires an elevated pulmonary venous pressure. Thus, diastolic dysfunction is clinically manifested as pulmonary congestion. Defined in this manner, the most common cause of diastolic dysfunction is systolic dysfunction. In fact, the most common symptom of patients with systolic dysfunction is dyspnea from the resulting diastolic dysfunction. Diastolic dysfunction in the setting of normal systolic function may be due to obstruction of left ventricular filling, impaired left ventricular distensibility, or extensive external compression of the LV. Treatment of diastolic dysfunction can be accomplished by relieving myocardial ischemia, improving systolic function, lowering arterial systolic pressure, and decreasing cardiac distention. Copyright ( 1993 by W.B. Saunders Company KEY WORDS: congestive heart failure, left ventricular tion, diastolic dysfunction

func-

ventricular dysfunction is defined as impaired emptying of the LV. This can be quantified as the LV emptying fraction or ejection fraction. The ejection fraction, calculated as stroke volume divided by LV end-diastolic volume, has been used as an index of myocardial contractile performance. However, the ejection fraction is not only influenced by myocardial contractility, it is also strongly influenced by the LV afterload.” LV afterload, in its simplest form, is the LV systolic pressure. Thus, a reduced ejection fraction may be due to either depressed myocardial contractility or increased LV afterload. In the presence of a left-sided valvular regurgitant lesion (mitral regurgitation or aortic regurgitation), or a ventricular septal defect, the LV stroke volume may be high, while the forward stroke volume (stroke volume minus regurgitant volume or shunt volume). which contributes to useful cardiac output, is much lower. Accordingly, the effective ejection fraction is defined as the forward stroke volume divided by end-diastolic volume. The effective ejection fraction was chosen to quantify systolic function since it rcprcsents the functional emptying of the LV and is relatively independent of LV end-diastolic volume over the clinically relevant range.’ An operational definition of systolic dysfunction is an effective ejection fraction of less than 50%‘. When defined in this manner. systolic LV dysfunction may result from impaired myocardial function, increased LV afterload, and/or structural abnormalities of the left heart as shown in Table 2. The forward stroke volume is equal to the effective ejection fraction times the end-diastolic volume. If LV contractile state and arterial properties remain constant as end-diastolic volume incrcascs, the ejection fraction stays constant or increases slightly.J An increase in the enddiastolic volume will allow for a normal stroke volume despite a reduced etfcctive ejection fraction. Thus, an important method of compensation for an impaired emptying (systolic dysfunction) is an increase in the LV enddiastolic volume. This is produced by the ncurohumoral mechanisms that result in an increase in vascular tone and intravascular volume in response to a fall in cardiac output. The resulting increase in the end-diastolic volume restores

Journalof Cardiothoracic and Vascular Anesthesia, Vol 7. No 4, Suppl 2 (August), 1993: pp 2-5 Sponsored by Sanofi Winthrop

CONGESTIVE

3

HEART FAILURE

0

Table 2. Classification of Heart Failure I. Systolic

Input

x ED sv = EF,mcnve Aftetioad

X

k?tii%ii”

HR

(Abnormal

2. Decreased myocardial

units

lschemic heart disease B. Increased Afterload Aortic stenosis, systemic C. Structural

&

SystolicFunction Dlastollc Functlon

function

Dilated cardiomyopathy

Volume

!?%ib”

Emptying)

Function

1. Decreased global myocardial

r?zcs:

Structure

Dysfunction

A. Loss of Contractile

hypertension

Abnormalities

Mitral and aortic regurgitation, II. Diastolic Dysfunction A. Systolic

ventricular

septal defect

(Elevated Filling Pressure)

Dysfunction

B. Obstruction

to Filling

Mitral stenosis,

left atrial myxoma

C. Decreased Distensibility Hypertrophic

cardiomyopathies

genital), aging, amyloid

Diastolic Dysfunction

In order for the LV to function as a pump, it must not only empty, but also fill. The left atria1 (and pulmonary venous) pressure is the source pressure for LV filling. Thus, normal LV diastolic function is defined as filling of the LV sufficient to produce a cardiac output commensurate with the body’s needs while maintaining a mean left atria1 pressure (and pulmonary venous pressure) less than 12 mmHg.h Maintenance of a normal forward stroke volume when the effective ejection fraction is decreased requires a larger end-diastolic volume. Thus, the amount of filling necessary to produce an adequate cardiac output depends on the LV systolic performance (as quantified by the effective ejection fraction). An abnormality of LV filling that would not produce an adequate cardiac output will activate compensatory mechanisms that elevate the pulmonary venous pressure. Thus, abnormalities of LV diastolic performance do not usually produce a reduction of cardiac Table 1. Congestive Heart Failure: Definitions Systolic dysfunction Decreased

( < 50%)

effective

volume/end-diastolic

ejection fraction

(forward stroke

volume)

Diastolic dysfunction Filling of the LV sufficient

to produce an adequate cardiac

output requires an elevated pulmonary (> 12 mmHg).

venous

pressure

concardiomy-

opathies

Fig 1. Block diagram of left heart performance. The pulmonary venous (PV) pressure is the input; the cardiac output is the output. The cardiac output is determined by the stroke volume (SV) x the heart rate (HR). Stroke volume is in turn determined by the effective ejection fraction (EF) x the end-diastolic (ED) volume. Abbreviations: LA, left atrium; MV, mitral valve.

the stroke volume towards normal, but this compensatory response will also elevate the pulmonary venous pressure and thus may produce pulmonary congestion. Chronically, the left ventricle may become more compliant. In this situation, the LV end-diastolic volume may be increased sufficiently to normalize the stroke volume despite the reduced effective ejection fraction, without an increase in pulmonary venous pressure.

(hypertension.

and other restrictive

D. Impaired Relaxation Familial hypertrophic

cardiomyopathy

E. External Compression Constrictive

pericarditis,

cardiac tamponade.

car pul-

monale

at rest; instead, pulmonary venous congestion is the most common result of diastolic dysfunction. A patient with systolic dysfunction (reduced effective ejection fraction) requires a larger end-diastolic volume in order to produce an adequate stroke volume and cardiac output. If the larger LV end-diastolic volume can be achieved without an abnormally high pulmonary venous pressure, this can compensate for impaired systolic performance. However, if the larger end-diastolic volume requires an elevation of pulmonary venous pressure, the systolic dysfunction (ie, reduced effective ejection fraction) will result in diastolic dysfunction. In this manner, systolic dysfunction is the most common cause of diastolic dysfunction. However, diastolic dysfunction commonly occurs in the absence of systolic dysfunction and may be due to obstruction of LV filling, impaired LV distensibility, or external compression of the LV (Table l).’ The most common cause of such primary diastolic dysfunction is altered diastolic distensibility. In the pressure-volume plane, this is represented by a leftward and upward shift of the end-diastolic pressure-volume relation (EDPVR). When this occurs, significantly higher pressures are required to sufficiently distend the LV to achieve the same end-diastolic volume. If the shift in the EDPVR is severe enough, filling of the LV to the level sufficient to produce a normal stroke volume can only be achieved with an elevated pulmonary venous pressure that will be associated with pulmonary congestion. Thus, an alteration in diastolic distensibility may produce pulmonary congestion and congestive heart failure in the absence of systolic dysfunction.’ Diastolic distensibility may be impaired by several different mechanisms. Impaired relaxation may result in persistent pressure generation at end-diastole, and may contribute to the altered diastolic distensibility observed in patients with hypertrophic cardiomyopathy and during ischemia.’

output

4

1, V Rdrrxatior~ As the LV begins to relax late in systole. LV prcsaurc falhi, ejection stops and the aortic valve closes as LV pressure falls below aortic pressure. As the force generated by the contractile elements falls, elastic elements compressed during the previous ejection recoil and the ventricle untwists.x,y As relaxation continues, LV pressure falls below left atrial pressure, and the mitral valve opens. Left ventricular pressure continues to fall, producing a pressure gradient that accelerates blood from the left atrium to the LV. “1 Although the process of LV relaxation is usually completed well before the end of diastole, most LV filling actually occurs early in diastole while the LV is relaxing. In fact, about one fourth of the stroke volume enters the LV while LV pressure is falling. tt Furthermore, approximately three quarters of the stroke volume enters the LV in the first third of diastole. Thus, the process of relaxation and elastic recoil are important in producing the explosive filling of the LV early in diastole. Exercise may enhance this process.‘? When LV relaxation is reduced, the filling of the LV is dependent on a vigorous atria1 contraction.“,‘3 If this left atria1 contraction is absent or inadequate, LV tilling will require an elevated mean left atria1 pressure. It is important to recognize that it is an elevation of mean left atrial pressure (not LV end-diastolic pressure) that produces pulmonary congestion. t4 Thus, changes in the rate of relaxation may have a clinically important influence on LV diastolic performance.h,‘5 Because contraction and relaxation are energy-requiring processes, both can be depressed by conditions such as ischemia that reduce myocardial adenosinc triphosphate (ATP) supplies. I3 Thus, acute ischemia may reduce LV pump performance both by decreasing systolic performance and slowing relaxation, which depresses diastolic performance. Patients with congestive cardiomyopathies may have both impaired contractile performance and slowed relaxation, perhaps due to a prolonged Ca++ transient.‘” Sympathetic stimulation and inotropic agents that incrcasc cyclic AMP increase both the speeds of contraction and relaxation.t7 However, contraction and relaxation do not always change together. For example, patients with hypertrophic cardiomyopathy may have supranormal LV systolic performance, slowed relaxation and diastolic dysfunction.‘“,‘” In addition, digitalis increases the force of contraction without speeding the rate of relaxation in normal myocardium.” The rate of LV relaxation also depends on the systolic load.” Not only is the magnitude of the systolic load important, but also when it is applied and its uniformity. In simplest terms, in the intact circulation, increases in systolic LV pressure tend to slow the rate of LV relaxation.” Eichhorn et a12’recently found that patients with the most impaired systolic performance not only had the slowest rate of relaxation, but also the most load-dependent relaxation. Why did Eichhorn et al observe that relaxation depends more strongly on systolic pressure in patients with depressed left ventricular systolic performance‘?

LITTLE AND APPLEGATE

A possible explanation is that greater changes m cndsystolic volume occur with changes in end-systolic prcasurc in these patients. The lower the systolic function, the greater the change in systolic ejection that will result from an alteration of systolic LV pressure. Systolic muscle length. which is determined by end-systolic volume. is an important determinant of relaxation rate.“‘.22.2’ In addition, the smaller the end-systolic volume, the greater the amount of energy that is stored during systolic ejection by comprcssing elastic elements and changing the configuration of the LV.x’ The release of this stored energy during relaxation may speed the rate of LV pressure fall and importantly contribute to early diastolic tilling. Thus. patients with reduced ejection fractions will rcspond to a fall in systolic pressure by increasing both their systolic LV performance and rate of relaxation. Such an enhancement in the rate of relaxation and a dccreasc in end-systolic volume would be expected to increase early diastolic mitral valve flow, potentially allowing LV filling at a lower mean left atria1 pressure.‘” Because the amount of pulmonary congestion is determined by the mean left atria1 pressure, this may decrease congestion even if the LV end-diastolic pressure is unchanged.” LV hypertrophy is also a common cause of impaired distensibility. Thus, the hypertrophy that can normalize wall stress and prevent systolic dysfunction in patients with aortic stenosis or hypertension, may result in decreased diastolic distensibility and produce diastolic dysfunction. Diastolic distensibility is also reduced as part of the normal aging process. Therefore, elderly patients who are also likely to have hypertension and ischcmia are at particular risk for diastolic dysfunction. Diastolic distensibility may also be altered by compression of the LV. For example. in cardiac tamponade the elevated pericardial pressure is transmitted into the LV cavity. If external compression by pericardial tamponade or constrictive pericarditis is severe enough, inadequate filling of the LV can result in a decrease in stroke volume. This is the usual mechanism responsible for the hypotension observed in acute cardiac tamponade. Acute cardiac distention may stress the pericardium and may also result in external compression of the LV.” Treatment of Diastolic Dysfitnction Diastolic dysfunction can bc improved by augmenting depressed systolic function if present. This will decrease the LV end-diastolic volume (and pulmonary venous pressure) required to generate an adequate cardiac output. Furthermore, improved systolic function will decrease LV endsystolic volume, speeding LV relaxation and enhancing elastic recoil, thus facilitating early diastolic filling. As discussed above, lowering arterial systolic pressure will also improve diastolic performance, especially if systolic performance is depressed. Other measures to enhance diastolic performance include decreasing cardiac dilation by diuresis, and relief of myocardial ischemia. ACKNOWLEDGMENT We thank Judy Fleurdnt assistance.

and Kathy Hurdle

for their secretarial

CONGESTIVE

5

HEART FAILURE

SUGGESTED Freeman

GL, Little WC, O’Rourke

agents

on

the

left

relation

in closed-chest

Ross J Jr: Afterload framework

ventricular

RA: The effect of vasoactive end-systolic

dogs. Circulation

mismatch

74:1107-l

and preload

for the analysis of ventricular

vast Dis 18:255-264, Sagawa K, Maughan volume relationship. Little WC. O’Rourke

pressure-volume 113, 1986

reserve:

A conceptual

function.

Prog Cardio-

1976 (suppl4) L. et al: Cardiac

contraction

and the pressure-

New York, NY, Oxford University, RA: Effect of regional

ischemia

1988

on the left

READING ventricular end-systolic pressure-volume relation in chronically instrumented dogs. J Am Coil Cardiol5:297-302, 1985 Sagawa K: The end-systolic pressure-volume relation of the ventricles: Definition, modification and clinical use. Circulation 63:12231227,198l Suga H, Kitabatake A, Sagawa K: End-systolic pressure determines stroke-volume from fixed end-diastolic volume in the isolated canine left ventricle under a constant contractile state. Circ Res 44~238-245, 1979 Weber KT, Janicki JS: The heart as a muscle-pump system and the concept of heart failure. Am Heart J 98:371-384, 1979 (suppl3)

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13. Grossman W: Diastolic dysfunction in congestive heart failure. N Engl J Med 325:1557-1564,199l 14. Braunwald E, Frahm CJ: Studies on Starling’s law of the heart (IV. Observations on the hemodynamic functions of the left atrium in man). Circulation 24:633-642, 1961 15. Little WC: Enhanced load dependence of relaxation in heart failure: Clinical implications. Circulation 85:2326-2328, 1992 16. Morgan JP, Erny RE, Allen PD, Grossman W, Gwathmey JK: Abnormal intracellular calcium handling, a major cause of systolic and diastolic dysfunction in ventricular myocardium from patients with heart failure. Circulation Sl:III-21-111-32, 1990 17. Little WC. Rassi A, Freeman GL: Comparison of effects of dobutamine and ouabain on left ventricular contraction and relaxation in closed-chest dogs. J Clin Invest 80:613-620.1987 IX. Gwathmey JK. Warren SE, Briggs GM, et al: Diastolic dysfunction in hypertrophic cardiomyopathy. J Clin Invest 87:10231031,1991 IO. Brutsaert DL, Sys SU: Relaxation and diastole of the heart. Physiol Rev 69:1228-1315. 1989 20. Gilbert JC. Glantz SA: Determinants of left ventricular filling and of the diastolic pressure-volume relation. Circ Res 64:827-852, 1989 21. Eichhorn EJ. Willard JE, Alvarez L. Kim AS, Glamann DB, Risser RC, Grayburn PA: Are contraction and relaxation coupled in patients with and without congestive heart failure‘? Circulation 852132-2139, 1992 22. Sys SU, Brutsaert DL: Determinants of force decline during relaxation in isolated cardiac muscle. Am J Physiol 257(Heart Circ Physiol26):H1490-H1497, 1989 23. Ter Keurs HEDJ, Rijnsburger WH, Heuningen RV, Nagelsmit MJ: Tension development and sarcomere length in rat cardiac trabeculae. Circ Res 46:703-714, 1980 24. Applegate RJ, Johnston WE, Vinten-Johansen J. Klopfenstein HS. Little WC: Restraining effect of intact pericardium during acute volume loading. Am J Physiol262:H1725-Hl733, 1992