(Circulation. 1996;93:67-73.)
© 1996 American Heart Association, Inc.
Articles |
Energetically Optimal Left Ventricular Pressure for the Failing Human Heart
From the Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Correspondence to Hidetsugu Asanoi, MD, The Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-01, Japan.
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Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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Background An energy-starved failing heart would benefit from more effective transfer of the mechanical energy of ventricular contraction to blood propulsion. However, the energetically optimal loading conditions for the failing heart are difficult to establish. In the present study, we analyzed the optimal left ventricular pressure to achieve maximal mechanical efficiency of the failing heart in humans.
Methods and Results We determined the relation between left ventricular pressure-volume area and myocardial oxygen consumption per beat (VO2), stroke work, and mechanical efficiency (stroke work/VO2) in 13 patients with different contractile states. We also calculated the optimal end-systolic pressure that would theoretically maximize mechanical efficiency for a given end-diastolic volume and contractility. Left ventricular pressure-volume loops were constructed by plotting the instantaneous left ventricular pressure against the left ventricular volume at baseline and during pressure loading. The contractile properties of the ventricle were defined by the slope of the end-systolic pressure-volume relation. In patients with less compromised ventricular function, the operating end-systolic pressure was close to the optimal pressure, achieving nearly maximal mechanical efficiency. As the heart deteriorated, however, the optimal end-systolic pressure became significantly lower than normal, whereas the actual pressure remained within the normal range. This discrepancy resulted in worsening of ventriculoarterial coupling and decreased mechanical efficiency compared with theoretically maximal efficiency.
Conclusions Homeostatic mechanisms to maintain arterial blood pressure within the normal range cause the failing heart to deviate from energetically optimal conditions.
Key Words: blood pressure • contractility • heart failure • mechanics • autonomic nervous system
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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Katz1 proposed that heart failure should be regarded as a cardiomyopathy of overload, a condition that leads to energy starvation and progressive deterioration of cardiac function. In this model, the effectiveness of transfer of the mechanical energy of ventricular contraction critically affects long-term prognosis in chronic heart failure. Thus, for transport of blood at a given pressure, it would be preferable to optimize stroke work, whereas from the viewpoint of cardiac energy expenditure, optimization of mechanical efficiency might be appropriate. Previous experimental and clinical studies2 3 4 5 6 have indicated that the cardiovascular system is normally regulated to maximize stroke work or mechanical efficiency. However, we have shown that the working point of the left ventricle deviated from both the optimal stroke work and mechanical efficiency in patients with severely depressed heart function. Under all circumstances, arterial blood pressure remained essentially the same, and severe hypotension was uncommon in chronic heart failure.6 7 The deterioration of energy transfer therefore may result from an adjustment in cardiovascular regulation to maintain arterial pressure within the physiological range. To date, the precise mechanisms responsible for ventriculoarterial mismatch to optimize stroke work or mechanical efficiency in heart failure remain to be identified.
The present study was designed to determine what mechanisms govern the ventriculoarterial coupling responsible for impaired energy transfer in chronic heart failure. We used the pressure-volume area (PVA) concept proposed by Suga et al,8 9 to predict the optimal left ventricular pressure that achieves maximal mechanical efficiency of the failing left ventricle. The PVA represents the total mechanical energy of contraction and correlates linearly with myocardial oxygen consumption per beat (VO2). This concept has a great advantage over previous predictors of mechanical energy utilization in analyzing the quantitative relation between loading and inotropic conditions and the mechanical efficiency of the diseased left ventricle.
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Methods |
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Study Patients
The study was performed in 13 male patients with a mean age of 51 years (range, 36 to 65 years). Seven patients had a previous myocardial infarction, five had cardiomyopathy (three idiopathic and two postmyocarditis), and one had atypical chest pain. Patients who showed clinical symptoms and signs of new myocardial ischemia on treadmill exercise testing or on exercise 201T1 myocardial perfusion scans were excluded from the study. Patients with a left ventricular aneurysm or mitral regurgitation also were excluded from the study. All patients were in normal sinus rhythm, and all medications were withheld for 24 hours before the procedure. The study protocol was reviewed and approved by the ethical committee of our institute, and informed written consent was obtained from each patient. There were no complications as a result of the study.
Catheterization Procedure
Cardiac catheterization was
performed using the
right brachial approach with the patients in a fasting state. After
conventional diagnostic right- and left-side heart
catheterization, coronary arteriography was
performed with the Sones technique. Proximal coronary sinus
catheterization was performed with a dual thermistor
thermodilution catheter (Webster Laboratory Inc).10 A
high-fidelity micromanometer-tipped
catheter (Micro-Tip, Millar Instruments) was then introduced into the
left ventricle, which allowed simultaneous
high-fidelity pressure measurement during arteriography. After
sufficient time had elapsed following coronary arteriography,
coronary sinus blood flow was determined in duplicate by a
standard thermodilution method. The position of the catheter was
verified by fluoroscopy during the study and by hand injection of small
doses of contrast medium to confirm that the proximal thermistor was
located right in the ostium of the coronary sinus.
Arterial and coronary sinus blood samples were
drawn simultaneously to determine oxygen saturation and
lactate concentration. Left ventricular cineangiography was
performed with the patient in the 30° right anterior oblique
projection with a Toshiba 9-in (22.86-cm) image intensification
system. Left ventricular opacification was achieved by
injecting 35 to 40 mL of radiopaque nonionic contrast agent (iopamidol)
through a Millar angiographic catheter at a rate of 12 mL/s. Films were
exposed at a rate of 60 frames per second with an Arriflex 35-mm cine
camera while the patient held his breath. During the cineangiographic
study, high-fidelity left ventricular pressure, ECG,
cineangiographic frame markers, and an injection marker were
recorded simultaneously.
An adequate recovery time (more than 15 minutes) was allowed for the left ventricular pressure to return to its baseline level. Phenylephrine (5 mg/100 mL) was given to increase the left ventricular peak pressure by about 40 mm Hg. In nine patients, the heart rate was maintained almost the same as in the control state by coronary sinus pacing. The measurements of coronary sinus flow and the sampling of coronary sinus blood were repeated under steady state conditions during pressure elevation. Following these measurements, a second cineventriculogram was obtained in the same manner as in the control state. Myocardial lactate uptake was calculated in eight patients as follows: Myocardial lactate uptake=(arterial lactate-coronary sinus lactate)x100/arterial lactate. There were no signs of pulmonary congestion, transient mitral regurgitation, or other side effects during these procedures.
Generation of Angiographic Pressure-Volume Diagrams
The
boundary of the ventricular silhouette was
delineated manually using the Oscon cine analyzer. Left
ventricular volume (V) was calculated by an area-length
method using a modified Kennedy's formula11 :
V=0.687xC3xA2/L+1.9, where A is
the
area of the ventricle calculated from the number of pixels surrounded
by the ventricular boundary, L is the longest measured
length between the midpoint of the aortic valve and the apex, and C is
the linear correction factor for the magnification of a unit of length
(1 pixel). The value for C was derived by comparing the area of filmed
grid with the known area of a 1-cm2 grid placed parallel to
the tube at the level of the heart. The calculated volume of each frame
was synchronized to the corresponding pressure throughout one cardiac
cycle using simultaneously recorded exposure markers to
obtain the pressure-volume loop.
Left Ventricular End-Systolic Pressure-Volume
Relation and Mechanical Energy
An end-systolic pressure-volume line
was drawn
on the top left corners of the pressure-volume loops of baseline
and pressure loading (Fig 1
). The left
ventricular contractile state was defined by the slope
(Ees) of this end-systolic pressure-volume
relation.12 13 We used planimetry to measure the PVA
at
baseline and during increased afterload and defined the PVA as the area
within the straight line connecting the volume-axis intercept
(Vo) of the end-systolic
pressure-volume line and the end-systolic point, the
end-diastolic pressure-volume relation curve, and
the systolic segment of the pressure-volume trajectory. The
PVA in an ejecting contraction consists of two parts (Fig
1).8 One part is the area within the
pressure-volume
loop trajectory (A-B-C-D-A) that equals left ventricular
external work (EW). The other part is the area between the
end-systolic and end-diastolic
pressure-volume curves on the left of EW (E-C-D-E). This area is
considered to be equal to the end-systolic elastic
potential energy built up and stored in the ventricular
wall during systole.
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, End-systolic P-V points. Ees and
Vo of the left ventricular
end-systolic P-V relation are determined by the P-V
diagrams at baseline and a high-pressure setting with
phenylephrine. The energetically optimal
end-systolic pressure is the point where mechanical
efficiency is theoretically maximized for a given
contractility and end-diastolic volume.
The pressure-volume area in the P-V diagram is the area
circumscribed by the end-systolic P-V line, the
end-diastolic P-V curve, and the systolic
segment of P-V trajectory (E-A-B-C-E). Left ventricular
external work is the area within the P-V loop (A-B-C-D-A).
Mechanical Efficiency and VO2-PVA
Relation
The determination of the VO2-PVA
relation has been described previously.14 In brief, the
oxygen contents of arterial and coronary sinus
blood were calculated as the product of the percent oxygen
saturation, the oxyhemoglobin binding capacity, and the hemoglobin
concentration. The VO2 was calculated as the
product of the coronary sinus blood flow and the
arteriocoronary sinus oxygen difference and was expressed
on a per-beat basis. Because the energy units of EW and
VO2 are expressed as mm Hg · mL and mL
O2, respectively. These units were converted into a
common unit of energy (J) with the following conversions: 1
mm Hg · ml=1.33x10-4 J and 1 mL
O2=20 J.
Mechanical efficiency was expressed conventionally as the ratio of EW
to VO2. For each patient, the
VO2 was plotted as a function of the PVA at
baseline and in high-pressure states. The slope (A) and
oxygen-axis intercept (B) of the relation between the
VO2 and PVA were determined from a straight
line connecting these two points (ie,
VO2=AxPVA+B) in the
same
manner as determined by Burkhoff et al.15
Theoretical Considerations
We examined how far the mechanical
efficiency
(EW/VO2) deviated from its maximal value as
contractility (Ees) decreased. We defined
the maximal mechanical efficiency as the theoretically obtained maximal
EW/VO2 value for a given
end-diastolic volume and ventricular
contractility using a method described
previously.16 17 18 To simulate the
EW/VO2 efficiency as a function of the
end-systolic pressure (ESP), we used the following
mathematical formulae to relate EW, PVA, and
end-diastolic volume (EDV):
 | (1) |
 | (2) |
 | (3) |
where
SV is stroke volume and PE is potential energy. In
Equation 1
, we assumed for simplicity that the mean
ventricular pressure during ejection was equal to the ESP
and that end-diastolic pressure is zero. The empirical
relation between the PVA and VO2 has been
formulated8 9 as follows.
 | (4) |
where
coefficient A is constant, regardless of
loading conditions and the Ees. Constant B is a
function of the Ees and is independent of loading
conditions.12 13 In the present simulation, we
adopted
the A and B values that were obtained through
linear regression analysis between the
VO2 and PVA in each patient. According to
earlier theoretical and experimental
studies,16 17 18
EW/VO2 can be expressed as a function of ESP
from Equations 1 through
4:
 | (5) |
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where
V is EDV-Vo. From Equation 5, the maximal
EW/VO2 value is given at
ESP=[-2xB+(4xB2+2xAxBxEesxV2)0.5]/
(AxV).
Statistical Analysis
Data are expressed as mean±SD.
Several investigators have
theoretically demonstrated that the relation between
EW/VO2 and ESP can be expressed as a convex
curve when EW/VO2 is more than
zero.16 17 18 Therefore, we applied a
hyperbolic relation to
compare EW/VO2 with ESP. Because patients
served as their own controls, the statistical significance of
differences in hemodynamic variables was tested
with a paired t test. Values of P<.05 were
considered statistically significant.
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Results |
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Changes in left ventricular and coronary hemodynamics observed with pressure manipulation are listed in Table 1
. The left ventricular peak
pressure increased by about 40 mm Hg with phenylephrine
and was associated with increases in left ventricular
end-diastolic and end-systolic volumes by
24% (P<.001) and 33% (P<.001), respectively.
Consequently, left ventricular ejection fraction fell by
6% (P<.05). Coronary sinus flow increased by 44%
(P<.001), but arteriocoronary sinus oxygen
difference did not change. Myocardial oxygen consumption per minute
increased by 47% (P<.001). Myocardial lactate uptake
increased in all eight patients, and there were no signs of myocardial
ischemia on the ECG during these interventions.
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Actual and theoretically maximal mechanical efficiencies and the
corresponding left ventricular end-systolic
pressures are listed in Table 2. Ees ranged
from 0.81 to 8.80 mm Hg/mL, and left ventricular ejection
fraction ranged from 30% to 70%. The slope coefficient A
of the VO2-PVA relation was constant, with a
mean value of 1.65x10-5 mL
O2/(mm Hg · mL) over the range of
Ees values. The oxygen-axis intercept B
tended to decrease as contractility declined. As the
heart failed, the theoretically maximal efficiency tended to increase,
whereas actual efficiency declined somewhat. Consequently, the
mechanical efficiency deviated considerably from the maximal in the
depressed heart (Fig 2). Fig 3
illustrates the actual and energetically optimal
end-systolic pressures plotted against the basal inotropic
states. The operating left ventricular
end-systolic pressure was close to the optimal pressure in
patients with an Ees of 4 to 6 mm Hg/mL. In patients with
more compromised cardiac function, however, the optimal
end-systolic pressure required to achieve maximal
efficiency was markedly lower than the actual operating
end-systolic pressure, which was maintained within the
normal range.
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)
declines to less than the operating pressure (
), which is
maintained within the normal range independent of basal
contractility. |
Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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The present study demonstrates that left ventricular mechanical efficiency in the failing human heart is always maximized at a lower end-systolic pressure than the normal pressure to maintain adequate systemic circulation. In contrast, the operating end-systolic pressure remained within the normal range in all patients studied. Consequently, as the heart failed, the operating mechanical efficiency was decreased relative to the maximally attainable efficiency for a given contractility and ventricular volume.
Energetically Optimal Left Ventricular
Pressure
Recently, we used the PVA concept to evaluate energy
conversion
efficiency in the human left ventricle and found that conventional
mechanical efficiency (EW/VO2) does not change
appreciably with depression of contractile states as long as left
ventricular pump function is not severely
compromised.14 However, our previous study did not examine
whether the actual mechanical efficiency was maximized for a given left
ventricular contractility and volume.
Several studies have attempted to define what conditions energetically
optimize coupling between the ventricle and arterial load
in vivo under healthy and pathological
conditions.2 3 4 5 6 17
With a model of ventricular and arterial
elastance based on pressure-volume data, Burkhoff and
Sagawa17 predicted theoretically that mechanical
efficiency is maximized when the arterial elastance is less
than the ventricular elastance. These analytical frameworks
qualitatively imply an optimal coupling condition between the left
ventricle and the arterial system. We previously showed
that ventricular elastance was less than one half of
arterial elastance in patients with severely depressed
cardiac function and that neither stroke work nor mechanical efficiency
was maximized.6 Clinically, heart failure is accompanied
by an increase in the end-diastolic volume and a
decrease in the Ees, both of which could affect the
mechanical efficiency of the left ventricle. To make the matter more
complex, the relative magnitude of the change in preload and
contractility cannot be controlled independently in an
individual patient. Under these conditions, the determination of the
energetically optimal arterial pressure requires a more
quantitative approach to relate mechanical efficiency to inotropic and
loading conditions.
Suga et al18 used the PVA concept to show that the mechanical efficiency of the excised canine left ventricle varied as an explicit function of preload, afterload, and contractility. That is, the theoretically attainable maximal efficiency increased with increases in preloaded end-diastolic volume. Similar relations were observed between mechanical efficiency and afterloaded ventricular pressures and between mechanical efficiency and contractility. This function allows us to predict the mechanical efficiency of the left ventricle under various loading and inotropic conditions, as well as to search for the loading and inotropic conditions that maximize the mechanical efficiency of the left ventricle.
To define quantitatively how far the actual mechanical efficiency deviated from the theoretically attainable maximal efficiency in each patient, we expressed mechanical efficiency as a function of left ventricular end-systolic pressure. We previously used this formula to examine energetically optimal end-systolic pressure in normal canine hearts.16 Similarly, we calculated the end-systolic pressure that would maximize mechanical efficiency for a given end-diastolic volume and contractility in each patient. This optimal end-systolic pressure fell below normal as the heart deteriorated, whereas the maximal mechanical efficiency tended to increase. The increase in the maximal efficiency of the failing heart was attributable largely to the increase in end-diastolic volume because the increase in preload raises the maximal efficiency, opposing the effects of depressed contractility.18
Neural Modulation of Ventriculoarterial
Coupling
Mechanisms responsible for the dissociation between actual
and
optimal left ventricular end-systolic pressures
appear to be related to the neurohumoral regulation that maintains
normal arterial pressure. In general, the body monitors the
adequacy of circulation by sensing arterial pressure and
responds in a stereotypical manner to maintain arterial
pressure within a preset range.19 20 This control is
mediated largely through the autonomic nervous system, which
innervates not only the heart but also the vascular system.
Recently, Kubota et al21 examined the influence of
reflex-mediated sympathetic discharge on
ventriculoarterial coupling and demonstrated that
ventricular and arterial elastance changed
synergistically to maintain normal arterial pressure when
the left ventricle and arterial system are intact. Such a
synergistical response of ventricular and vascular
properties seems to preserve optimal ventriculoarterial
coupling under normal conditions. However, we previously suggested that
when the responsiveness of either the ventricle or the
arterial system is suppressed, as is the case when
vasoactive agents are administered or cardiac
contractility is depressed, the unaffected part of the
cardiovascular system must bear the brunt of the
body's requirement to maintain normal pressure.6 Thus,
the pressure regulatory mechanisms could augment ventriculoarterial
mismatch under the condition of limited cardiovascular
reserve.7 In heart failure, for instance, the loss of
cooperative adaptation of the ventricle and arterial system
could result in a relative increase in arterial elastance
compared with ventricular elastance, where
arterial pressure is maintained within the normal range at
the expense of mechanical efficiency. Thus, negative feedback from the
autonomic nervous system to maintain normal arterial
pressure appears to dominate the optimization of left
ventricular mechanical efficiency in vivo.
Therapeutic Implications
For the energy-starved failing
heart, the effective transfer
of mechanical energy of ventricular contraction is
considered to have a crucial effect on long-term prognosis. The
present results suggest two strategies to optimize mechanical
efficiency of the failing left ventricle (Fig 4). The
first approach is to reduce the operating end-systolic
pressure toward the energetically optimal pressure without changing
contractility. Pharmacologically, this can be achieved
in one way by the administration of vasodilators. When
pressure-raising mechanisms have been activated as with the
case with chronic heart failure, drugs that interfere with these
systems directly—angiotensin-converting enzyme
inhibitors—seem the logical choice to decrease
end-systolic pressure. Recently, large clinical trials have
documented that long-term treatment with such agents improves the
prognosis of patients with chronic heart
failure.22 23 24 On
the other hand, although direct arterial vasodilators and
calcium channel blockers unload the heart, they also activate
the sympathetic nervous system and renin-angiotensin
system. The systemic vasoconstriction and salt retention produced by
these endogenous neurohumoral mechanisms may cause a
dissociation between actual and optimal end-systolic
pressures. The next step in this cascade is the restoration of cardiac
overload, the deterioration of effective energy transfer of the left
ventricle, and then acceleration of disease progression. This
hypothesis is supported by the observation that long-term
administration of potent arterial vasodilators has
deleterious effects in patients with chronic heart
failure.25 26 27
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Another strategy to optimize the mechanical efficiency of the failing heart is to increase the optimal end-systolic pressure toward the normal range. This corresponds to the use of inotropic agents. Augmentation of contractility could optimize mechanical efficiency of the failing heart while maintaining normal arterial pressure and potentially attenuate endogenous neurohumoral activity.28 We demonstrated in an open-chest canine model that an augmentation of contractility with dobutamine can restore the afterload-induced deterioration of mechanical efficiency toward the maximal level.16 Unfortunately, most clinical trials of inotropic agents have demonstrated that prolonged inotropic stimulation of the failing heart has an adverse effects on the long-term survival of severely ill patients.29 30 31 Drugs that produce this effect—the ß-adrenergic agonists and the phosphodiesterase inhibitors—could increase intracellular cAMP and endogenous neurohumoral activity, undermining the beneficial effect of enhanced contractility over time. Proarrhythmic effects, relating to the rise in the cytosolic calcium concentration, are other potential hazards associated with the use of these agents. However, these adverse experiences may not be true of all inotropic agents, particularly those with mechanisms in addition to or independent of phosphodiesterase inhibition.
Recently, new inotropic agents with unique mixed mechanisms of action have been developed and tested clinically. Vesnarinone affects ion channels and the phosphodiesterase enzyme and improves cardiac function in acute and chronic heart failure.32 33 Quite recently, this agent has been shown to improve the quality of life and decrease the morbidity and mortality of patients with heart failure.34 Pimobendan, which sensitizes the contractile proteins to intracellular calcium and inhibits phosphodiesterase, also appears to be beneficial in long-term treatment.35 36 Clinical trials of both vesnarinone and pimobendan suggest that with the use of appropriate doses, these new drugs might improve morbidity of the patient with heart failure, minimizing the adverse effects of increased cAMP concentration and endogenous neurohumoral activation. Among drugs currently available for the treatment of heart failure, digitalis is ideal in terms of optimizing the mechanical efficiency of the failing heart because it attenuates pressure-raising mechanisms by restoring the sympathetic-parasympathetic autonomic balance and reducing renin secretion and increases the optimal end-systolic pressure toward normal by enhancing left ventricular contractility. Recently, there has been growing evidence to demonstrate the usefulness of digoxin in the long-term treatment of chronic heart failure.37 38
Study Limitations
Several methodological problems must be
considered in interpreting
the results of this study. Because volume data from left
ventriculography were limited, we derived the relationship between PVA
and VO2 from only two pressure settings in each
subject: the baseline pressure and a relatively high pressure. This
analysis uses the fact that despite the great difference in
heart size, a close linear correlation between
VO2 and PVA has been demonstrated in dog
hearts39 and in rabbit hearts.40 Minor
fluctuations in contractility due to increasing
arterial pressure cannot be excluded. In this regard, we
have shown previously in conscious dogs that pharmacological elevation
of arterial pressure did not appreciably change the slope
of the end-systolic pressure-volume
relation.7 Pressure loading potentially may cause
transient mitral regurgitation, which might affect the
increase in VO241 and the change
in mechanical efficiency because mitral regurgitation
increases left ventricular flow work. However, there were
no signs of mitral regurgitation either at baseline or
during pressure elevation. Recent evidence indicates that ionic
contrast medium can alter myocardial metabolism by
increasing free fatty acid uptake by the myocardium while
decreasing the myocardial uptake of glucose and lactate.42
In the present study, we performed left ventriculography using a
nonionic contrast agent that has low myocardial toxicity. Also, more
than 15 minutes were allowed between two ventriculographies. Therefore,
we believe that the effects of contrast medium on cardiac
performance and metabolism were minimized in this
study. We calculated the maximal stroke work as a rectangular area,
with its height being the end-systolic pressure and its
width the stroke volume. Even if this simple assumption had some
estimation error, quantitative factors probably would have little
effect on the directional changes in maximal stroke work because a
close correlation exists between left ventricular
end-systolic pressure and mean systolic pressure.
The present study did not take into account the effects of
coronary circulation on ventricular
contractility. Sunagawa et al43 have shown
in excised canine hearts that lowering the arterial
pressure below 67 mm Hg depresses contractility.
Therefore, the present findings should be considered valid only in
the pressure range as long as coronary perfusion is not
impaired. Finally, because of the small number and the
heterogeneity of our patients, the data were somewhat
scattered and could contain a modest quantitative error. However, the
hemodynamic changes seen in our study were relatively
uniform during pressure manipulation. Therefore, quantitative factors
probably should not affect the qualitative conclusions.
Conclusions
As the heart fails, the energetically optimal
end-systolic pressure decreases, while the actual pressure
remains normal. This discrepancy leads to worsening of the
ventriculoarterial coupling and decreases mechanical
efficiency relative to the maximal mechanical efficiency. The
present results suggest that energetically optimal conditions for
the failing heart may be achieved by bringing the operating
end-systolic pressure close to the optimal pressure or vice
versa without activating endogenous pressure-raising
mechanisms. Further investigations are warranted to confirm whether
this conceptual framework offers new therapeutic strategies in the
long-term treatment of heart failure.
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Acknowledgments |
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We greatly appreciate the continuous encouragement and valuable suggestions of Prof Shigetake Sasayama of the Third Department of Internal Medicine, Kyoto University, School of Medicine, Kyoto, Japan.
Received January 5, 1995; revision received August 10, 1995; accepted August 20, 1995.
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References |
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|
TopAbstractIntroductionMethods Results Discussion References |
|---|
1. Katz AM. Cardiomyopathy of overload: a major determinant of prognosis in congestive heart failure. N Engl J Med. 1990;322:100-110. [Medline] [Order article via Infotrieve]
2.
Sunagawa K, Maughan WL, Sagawa K. Optimal
arterial resistance for the maximal stroke work studied in
isolated canine left ventricle. Circ Res. 1985;56:586-595.
3.
Van den Horn GJ, Westerhof N, Elzinga G.
Optimal power generation by the left ventricle: a study in the
anesthetized open thorax cat. Circ
Res. 1985;56:252-261.
4.
Myhre ESP, Johansen A, Bjornstad J, Piene H.
The effect of contractility and preload on
matching between the canine left ventricle and afterload.
Circulation. 1986;73:161-171.
5. Toorop GP, Van den Horn GJ, Elzinga G, Westerhof N. Matching between feline left ventricle and arterial load: optimal external power or efficiency. Am J Physiol. 1988;254:H287-H295.
6.
Asanoi H, Sasayama S, Kameyama T.
Ventriculoarterial coupling in normal and
failing heart in humans. Circ Res. 1989;65:483-493.
7.
Asanoi H, Ishizaka S, Kameyama T, Sasayama S.
Neural modulation of ventriculoarterial coupling
in conscious dogs. Am J Physiol. 1994;266:H741-H748.
8.
Suga H. Total mechanical energy of a ventricle
model and cardiac oxygen consumption. Am J Physiol. 1979;236:H498-H505.
9. Suga H, Hayashi T, Shirohata M, Suehiro S, Hisano R. Regression of cardiac oxygen consumption on ventricular pressure-volume area of dog. Am J Physiol. 1981;240:H320-H325.
10.
Ganz W, Tamura K, Marcus HS, Dosono R, Yoshida S, Swan
HJC. Measurement of coronary sinus blood flow by
continuous thermodilution in man.
Circulation. 1971;44:181-195.
11. Kennedy JW, Trenholme SE, Kasser IS. Left ventricular volume and mass from single plane angiogram: a comparison of anteroposterior and right anterior oblique methods. Am Heart J. 1970;80:343-352. [Medline] [Order article via Infotrieve]
12.
Suga H, Sagawa K, Shoukas AA. Load independence
of the instantaneous pressure-volume ratio of the canine left
ventricle and effects of epinephrine and heart rate on the
ratio. Circ Res. 1973;32:314-322.
13. Suga H, Sagawa K. Instantaneous pressure-volume relationships and their ratio in the excised, supported canine left ventricle. Circ Res. 1974;35:314-322.
14.
Kameyama T, Asanoi H, Ishizaka S, Yamanishi K, Fujita
M, Sasayama S. Energy conversion efficiency in human left
ventricle. Circulation. 1992;85:988-996.
15. Burkhoff D, Yue DT, Oikawa RY, Franz MR, Schaefer J, Sagawa K. Influence of ventricular contractility on non-work related myocardial oxygen consumption. Heart Vessels. 1987;3:66-72. [Medline] [Order article via Infotrieve]
16.
Nozawa T, Wada O, Ishizaka S, Asanoi H, Fujita M,
Sasayama S. Dobutamine improves
afterload-induced deterioration of mechanical efficiency
toward maximal. Am J Physiol. 1992;263:H1201-H1207.
17.
Burkhoff D, Sagawa K. Ventricular
efficiency predicted by an analytical model. Am J
Physiol. 1986;250:R1021-R1027.
18. Suga H, Igarashi Y, Yamada O, Goto Y. Mechanical efficiency of the left ventricle as a function of preload, afterload, and contractility. Heart Vessels. 1985;1:3-8. [Medline] [Order article via Infotrieve]
19.
Harris P. Congestive heart failure: central role
of the arterial blood pressure. Br Heart
J. 1987;58:190-203.
20.
Anand IS, Ferrari DR, Kalra GS, Wahi PL, Poole-Wilson
PA, Harris PC. Edema of cardiac origin: studies of body water
and sodium, renal function, hemodynamic indexes, and
plasma hormones in untreated congestive cardiac failure.
Circulation. 1989;80:299-305.
21.
Kubota T, Alexander J, Itaya R, Todaka K, Sugimachi M,
Sunagawa K, Takeshita A. Dynamic effect of carotid sinus
baroreflex on ventriculoarterial coupling studied in
anesthetized dogs. Circ Res. 1992;70:1044-1053.
22. The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med. 1987;316:1429-1435. [Abstract]
23. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991;325:293-302. [Abstract]
24. Waagstein F, Bristow MR, Swedberg K, Camerini F, Fowler MB, Silver MA, Gilbert EM, Johnson MR, Goss FG, Hjaimarson A, for the Metoprolol in Dilated Cardiomyopathy (MCD) Trial Study Group. Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Lancet. 1993;2:1441-1446.
25.
Franciosa JA, Jordan RA, Wilen MM, Ledy CL.
Minoxidil in patients with chronic heart failure: contrasting
hemodynamic and clinical effects in a controlled
trial. Circulation. 1984;70:63-68.
26.
Goldstein RF, Boccuzzi SJ, Cruess D, Nattel S, the
Adverse Experience Committee, and the Multicenter Diltiazem
Postinfarction Research Group. Diltiazem increases
late-onset congestive heart failure in postinfarction patients with
early reduction in ejection fraction.
Circulation. 1991;83:52-60.
27.
Elkayam U, Amin J, Mehra A, Vasquez J, Weber L,
Rahimtoola SH. A prospective, randomized, double-blind,
crossover study to compare the efficacy and safety of chronic
nifedipine therapy with that of isosorbide dinitrate and
their combination in the treatment of chronic congestive heart
failure. Circulation. 1990;82:1954-1961.
28. Colucci WS, Denniss AR, Leatherman GF, Quigg RJ, Ludmer PL, Marsh JD, Gauthier DF. Intracoronary infusion of dobutamine to patients with and without severe congestive heart failure: dose-response relationships, correlation with circulating catecholamine, and effect of phosphodiesterase inhibition. J Clin Invest. 1988;81:1103-1110.
29. Dies F, Lilly E, Whitlow P, Liang C, Goldenberg I, Applefeld MM, Gilbert EM. Intermittent dobutamine in ambulatory out-patients with chronic heart failure. Circulation. 1986;74(suppl II):II-38. Abstract.
30.
Uretsky BF, Jessup M, Konstam MA, Dec GW, Leier CV,
Bemotti J, Murali S, Herrmann HC, Sandberg JA, for the Enoximone
Multicenter Trial Group. Multicenter trial of oral enoximone in
patients with moderate to moderately severe congestive heart failure:
lack of benefit compared with placebo.
Circulation. 1990;82:774-780.
31. Packer M, Carver JR, Rodeheffer RJ, Ivanhoe RJ, DiBianco R, Zeldis SM, Hendrix GH, Bommer WJ, Elkayam U, Kukin ML, Mallis GI, Sollano JA, Shannon J, Tandon PK, DeMets DL, for the PROMISE Study Research Group. Effect of oral milrinone on mortality in severe chronic heart failure. N Engl J Med. 1991;325:1468-1475. [Abstract]
32. Asanoi H, Sasayama S, Iuchi K, Kameyama T. Acute hemodynamic effects of a new inotropic agent (OPC-8212) in patients with congestive heart failure. J Am Coll Cardiol. 1987;9:865-871. [Abstract]
33. Asanoi H, Sasayama S, Kameyama T, Ishizaka S, Iuchi K. Sustained inotropic effects of a new cardiotonic agent: OPC-8212 in patients with chronic heart failure. Clin Cardiol. 1989;12:133-138. [Medline] [Order article via Infotrieve]
34.
Feldman AM, Bristow MR, Parmley WW, Carson PE, Pepin
CJ, Gilbert EM, Strobeck JE, Hendrix GH, Powers ER, Bain RP, White BG,
for the Vesnarinone Study Group. Effects of vesnarinone on
morbidity and mortality in patients with heart failure.
N Engl J Med. 1993;329:149-155.
35.
Kubo SH, Gollub S, Bourge R, Rahko P, Cobb F, Jessup M,
Brozena S, Brodsky M, Kirlin P, Shanes J, Konstam M, Gradman A,
Morledge J, Cinquegrani M, Singh S, LeJemtel T, Nicklas J, Troha J,
Cohn J, for the Pimobendan Multicenter Research Group.
Beneficial effects of pimobendan on exercise tolerance and
quality of life in patients with heart failure: results of a
multicenter trial. Circulation. 1992;85:942-949.
36. Sasayama S, Asanoi H, Kihara Y, Yokawa S, Terada Y, Yoshida S, Ejiri M, Horikoshi I. Clinical effects of long-term administration of pimobendan in patients with moderate congestive heart failure. Heart Vessels. 1992;9:113-120.
37. DiBianco R, Shabetai R, Kostuk W, Moran J, Schlant RC, Wright R, for the Milrinone Multicenter Trial Group. A comparison of oral milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure. N Engl J Med. 1989;320:677-683. [Abstract]
38.
Packer M, Gheoghiade M, Young JB, Constantini PJ, Adams
KF, Cody RJ, Smith LK, Voorhees LV, Gourly LA, Jolly MK, for the
RADIANCE study. Withdrawal of digoxin from patients with chronic
heart failure treated with angiotensin-converting
enzyme inhibitors. N Engl J
Med. 1993;329:1-7.
39.
Nozawa T, Yasumura Y, Futaki S, Tanaka N, Igarashi Y,
Goto Y, Suga H. Relation between oxygen consumption and
pressure-volume area of in situ dog heart. Am J
Physiol. 1987;253:H31-H40.
40.
Goto Y, Slinker BK, LeWinter MM. Similar
normalized Emax and O2 consumption-pressure-volume
area relation in rabbit and dog. Am J Physiol. 1988;255:H366-H374.
41.
Urschel CW, Covell JW, Graham TP, Clancy RL, Ross J,
Sonnenblick EH, Braunwald E. Effects of acute valvular
regurgitation on the oxygen consumption of the canine
heart. Circ Res. 1968;23:33-43.
42. Wisneski JA, Gertz EW, Neese RA, Morris DL. Absence of myocardial biochemical toxicity with nonionic contrast agent (iopamidol). Am Heart J. 1985;110:609-617. [Medline] [Order article via Infotrieve]
43.
Sunagawa K, Maughan WL, Friesinger G, Guzman PA, Cheng
M, Sagawa K. Effects of coronary arterial
pressure on left ventricular end-systolic
pressure-volume relations of isolated canine heart.
Circ Res. 1982;50:727-734.
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