(Hypertension. 1995;26:815.)
© 1995 American Heart Association, Inc.
Articles |
Contribution of Atrial Reservoir Function to Ventricular Filling in Hypertensive Patients
Effects of Nifedipine Administration
From the First Department of Medicine, Osaka University School of Medicine, Suita, and Osaka Minami National Hospital (M.N.), Kawachinagano, Japan.
Correspondence to Tohru Masuyama, MD, First Department of Medicine, Osaka University School of Medicine, 2-2 Yamadaoka, Suita 565, Japan.
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Abstract |
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Abstract We designed this study to assess the importance of left atrial function as a contributor to mitral flow velocity pattern in hypertensive patients. In hypertensive patients the early diastolic flow velocity and ratio of early to late diastolic flow velocity in the mitral flow velocity pattern increase in association with sublingual administration of nifedipine. These changes have been interpreted as signs of improved left ventricular diastolic function; however, the mitral flow velocity pattern is also affected by various other factors. Thus, the nifedipine-induced changes may not necessarily indicate the improvement of left ventricular diastolic function. Transthoracic Doppler echocardiographic parameters of mitral and pulmonary venous flow velocity patterns and left ventricular M-mode echograms were obtained in 16 untreated hypertensive patients before and after sublingual administration of nifedipine (10 mg). Normal values of the parameters were determined in 50 age-matched healthy subjects. After nifedipine peak early diastolic mitral flow velocity increased beyond the normal value, although the peak increasing rate of left ventricular inner dimension, another index of left ventricular diastolic function, did not recover to the normal value. Peak systolic velocity in the pulmonary venous flow velocity pattern increased beyond the normal value, indicating improvement of the reservoir function of the left atrium during systole. Nifedipine-induced normalization of the mitral flow velocity pattern was associated with further abnormalities of the pulmonary venous flow velocity pattern, indicating enhanced left atrial reservoir function. Thus, nifedipine-induced normalization of the mitral flow velocity pattern should be explained not only by the normalization of left ventricular diastolic function but also by another adaptive alteration in left atrial reservoir function in hypertensive patients. Combined analysis of mitral and pulmonary venous flow velocity patterns may be useful in avoiding the misinterpretation of the mitral flow velocity pattern.
Key Words: blood flow velocity • atrial function, left • hemodynamics • ventricular function • nifedipine • relaxation • echocardiography
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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The mitral flow velocity pattern has been analyzed for estimating left ventricular (LV) diastolic function and/or its serial changes in subjects with and without cardiac disease.1 2 3 Specifically, increases in early diastolic flow velocity, the ratio of early to late diastolic flow velocity, and the shortening of isovolumic relaxation time in the mitral flow velocity pattern have been interpreted as signs of improvement in LV diastolic function.4 5 This analysis has been used to clarify the impaired LV diastolic function in hypertensive patients and also to assess the changes in LV diastolic function associated with the administration of the calcium channel blocker nifedipine.6 7 8 However, the mitral flow velocity pattern is also affected by many other factors, such as left atrial pressure, LV systolic function, and LV minimum pressure.9 10 11 12 Thus, the increases in early diastolic flow velocity or the ratio of early to late diastolic flow velocity associated with nifedipine administration may not necessarily indicate improvement of LV diastolic function. In fact, two studies showed that the drug-induced increases in early diastolic flow velocity and/or the ratio of early to late diastolic flow velocity were caused by the change in loading conditions rather than in LV diastolic function.13 14
Recently, pulmonary venous flow velocity patterns have been obtained with the transthoracic approach. Because the pulmonary venous flow velocity pattern is more sensitive to changes in left atrial performance, its measurement is likely to provide a better understanding of changes in the mitral flow velocity pattern.15 16 17 18 In the present study we analyzed the transthoracic pulmonary venous flow velocity pattern, in addition to the mitral flow velocity pattern, before and after sublingual administration of nifedipine to obtain a better understanding of the nifedipine-induced change in the mitral flow velocity pattern in hypertensive patients. Specifically, we tested the hypothesis that left atrial performance may at least partially account for the nifedipine-induced change in the mitral flow velocity pattern.
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Methods |
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Study Population
Seventeen patients with untreated hypertension were considered for this study. None of them had pulmonary congestion diagnosed on chest roentgenograms. One patient was excluded because of inadequate transthoracic echo imaging. No patient had angina pectoris, and two-dimensional echocardiographic studies detected no regional wall motion abnormalities. Therefore, 16 patients (10 men, 6 women; age range, 28 to 70 years; mean, 54 years) with hypertension were enrolled in the study. An adequate LV M-mode echogram could not be obtained in 1 of the 16 patients. All patients were in sinus rhythm. Each patient gave informed consent, and the protocol of the study was approved by the Human Subjects Committee of the institution. Fifty volunteers (25 men, 25 women; age range, 25 to 77 years; mean, 52 years) without evidence of cardiovascular disease served as age-matched healthy subjects for determination of normal values of Doppler echocardiographic parameters. The volunteers fulfilled the following criteria: no history of heart disease or hypertension, normal blood pressure, and normal physical examination; no hyperlipidemia; normal electrocardiogram, chest x-ray study, and screening ergometer exercise test; normal M-mode, two-dimensional, and Doppler echocardiograms; and adequate Doppler echocardiographic recordings of mitral and pulmonary venous flow velocity patterns.
Study Protocol
Patients were studied with two-dimensional, M-mode, and
Doppler echocardiography initially in the left
lateral position. Nifedipine (10 mg) was then administered
sublingually. Echocardiographic study was repeated 30
minutes after nifedipine administration.
Echocardiographic Measurements
A commercially available echocardiograph (Toshiba
SSH-270HG) and a transducer array of 3.75 or 2.5 MHz were used. All
patients were examined by two-dimensional and M-mode
echocardiography for assessment of chamber size,
wall thickness, and wall motion.19 No patient showed
Doppler evidence of mild to severe aortic and/or mitral
regurgitation. Velocity recordings were made at
a paper speed of 100 mm/s, with simultaneous
recordings of the electrocardiogram and
phonocardiogram. Pulmonary venous flow velocity patterns at 1
to 2 cm beyond the orifice into the right upper pulmonary vein
were obtained in the apical four-chamber view with the guidance of
Doppler color-flow imaging (Fig 1). Mitral flow velocity patterns were
obtained after the pulmonary venous flow velocity
recording in the apical four-chamber view with the sample
volume placed carefully between the tips of the mitral leaflets, where
the maximal flow velocity in early diastole was obtained.
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Data Analysis
Data analysis was performed without any information of
the patient’s profile or other data of the study. Echoes of the
posterior wall and septal endocardium in LV M-mode echocardiograms,
recorded at a paper speed of 100 mm/s, were manually traced with an
image-analysis system (Kontron Elektronik) to obtain
instantaneous dimension over time and its first derivative
(dD/dt).20
Flow velocity recordings were analyzed by a digitizing pad (Graphtec) interfaced with a computer system (NEC PC-9800) for measurement of velocities and time intervals. Pulmonary venous flow velocity profiles were traced by hand along the instantaneous highest velocity spectra for determination of peak forward flow velocities during systole and diastole and peak reverse flow velocity at atrial contraction. The mitral flow velocity profiles were also traced by hand along the instantaneous highest velocity spectra for determination of peak early diastolic flow velocity, peak filling velocity at atrial contraction, and the deceleration time of the early diastolic filling wave (Fig 2). Isovolumic relaxation time was measured from the aortic valve closure on the phonocardiogram to the start of the mitral flow. The average values of five to seven consecutive cardiac cycles were used for quantitative analysis.
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Statistical Analysis
Results are expressed as mean±SD.
Echocardiographic parameters were compared
with the use of commercially available statistical software
(STATVIEW II, Abacus Concepts). ANOVA and Scheffé’s
test were used to test the significance of differences between subsets
and between variables before and after nifedipine. A
value of P<.05 was considered statistically
significant.
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Results |
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The Table summarizes echocardiographic parameters before and after sublingual administration of nifedipine in 16 hypertensive patients. Normal values were determined in 50 age-matched healthy subjects (Fig 3).
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P<.05 vs
prenifedipine.
M-Mode Echocardiographic
Parameters
Nifedipine administration did not produce changes in
LV dimensions or percent fractional shortening of LV diameter.
Decreased peak +dD/dt was significantly improved by
nifedipine administration, but the mean value was still
significantly lower than normal values.
Mitral Flow Velocity Patterns
Before nifedipine administration the peak filling
velocity at atrial contraction and the ratio of early to late
diastolic flow velocity were significantly higher, and
isovolumic relaxation time and deceleration time were significantly
longer than normal values. After nifedipine administration
both early and late diastolic flow velocities significantly
increased, and early diastolic flow velocity was slightly
though not statistically significantly greater than the normal
value.
Pulmonary Venous Flow Velocity Patterns
Before nifedipine administration peak forward flow
velocity during systole and peak reverse flow velocity at atrial
contraction were significantly higher, and the ratio of peak forward
flow velocity during systole to diastole was slightly
higher than the normal values. In association with
nifedipine administration peak forward flow velocity during
systole and peak reverse flow velocity at atrial contraction increased
further. Peak forward flow velocity during systole after
nifedipine administration was beyond the normal value, but
peak forward flow velocity during diastole did not
change.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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We analyzed mitral and pulmonary venous flow velocity patterns before and after sublingual administration of nifedipine in hypertensive patients to assess the contribution of LV diastolic function and left atrial function to the mitral flow velocity pattern. The nifedipine-induced normalization of mitral flow was associated with further abnormalities of pulmonary venous flow; thus, the normalization of mitral parameters could not be explained simply as the normalization of LV diastolic function. The nifedipine-induced changes in the pulmonary venous flow velocity pattern indicated enhancement of left atrial reservoir function. This finding strongly suggests the importance of left atrial reservoir function as a contributor to the mitral flow velocity pattern in hypertensive patients.
Effect of Nifedipine on LV Diastolic
Function
Improvement of LV diastolic function with
nifedipine administration has been described with the use
of pressure data in a variety of diseases.21 22 23 However,
the improvement was partial, and LV diastolic function did
not recover to normal levels in any of these studies. Although the
effect has not been studied in hypertensive patients, our data of LV
+dD/dt strongly suggest incomplete improvement of LV
diastolic function. Thus, although nifedipine
might improve LV diastolic function, the effect is unlikely
to be enough to normalize it.
Effect of Nifedipine on Mitral Flow Velocity
Pattern
Early diastolic mitral flow velocity increased beyond
the normal level in association with sublingual administration of
nifedipine despite presumed incomplete improvement of LV
diastolic function. The early diastolic mitral
flow filling wave consists of two components of blood: one reserved in
the left atrium during systole and the other conducted through the left
atrium during diastole.24 Improved LV
diastolic function mainly enhances the latter component,
and an increase in early diastolic mitral flow velocity is
attributed to enhancement of either component. Thus, an increase in
early diastolic mitral flow does not necessarily indicate
improved LV diastolic function, and the contribution of
these components can be quantified with parameters of
pulmonary venous systolic and diastolic
flows.
Effect of Nifedipine on the Pulmonary Venous
Flow Velocity Pattern
Pulmonary venous peak forward flow velocity during systole
increased beyond the normal value after nifedipine
administration. On the other hand, peak forward flow velocity during
diastole did not change. The pulmonary venous
systolic wave reflects left atrial reservoir function because
during systole the mitral valve is closed and the left atrium works as
a reservoir.24 25 The increase in peak forward flow
velocity during systole in association with nifedipine
indicates the increase of left atrial reservoir function. Thus, the
nifedipine-induced increase in early
diastolic mitral flow velocity is likely due to enhancement
of left atrial reservoir function rather than to improvement of LV
relaxation. This idea is also supported by the finding concerning
pulmonary venous diastolic flow velocity. If the
increase in early diastolic mitral flow velocity really
reflected improvement of LV relaxation and were associated with
emptying of the left atrium, peak forward flow velocity during
diastole in pulmonary venous flow should increase
in proportion to the increase in early diastolic flow
velocity, because during diastole the left atrium works as
a conduit between the left ventricle and pulmonary
vein.26 In the present study the increase in early
diastolic flow velocity was not accompanied by an increase
in peak forward flow velocity during diastole, suggesting
that the emptying of the left atrium in early diastole was
constant despite increased transmitral flow.
Left Atrial Reservoir Function
In hypertensive patients without congestive heart failure peak
forward flow velocity during systole and the ratio of systolic
to diastolic flow velocity were higher than these values in
healthy subjects.18 These abnormalities are considered to
be caused by the diastolic dysfunction and concomitant
systolic hyperfunction of the left ventricle.27 If
sublingual administration of nifedipine really improved LV
diastolic performance, the pulmonary venous
flow velocity pattern should recover to the normal pattern. However,
mean peak forward flow velocity during systole and the ratio of peak
forward flow velocity during systole to diastole increased
even further after nifedipine administration.
The mechanism of the enhancement of left atrial reservoir function by nifedipine administration in hypertensive patients is unknown. One possibility is increased (supernormalized) LV systolic performance associated with rapid reduction in LV afterload after nifedipine administration. Left atrial reservoir function reflects a passive rather than active process of the left atrium.24 26 Thus, left atrial reservoir function may be related to LV systolic performance.
It is unclear whether nifedipine enhances left atrial reservoir function in healthy subjects or in patients with other cardiac diseases in a similar fashion. However, in healthy subjects sublingual administration of nifedipine does not significantly affect the ratio of peak early to late diastolic flow velocity in mitral flow velocity patterns.6 Thus, the effects of nifedipine on LV diastolic and left atrial reservoir functions may likely be different between hypertensive patients and healthy subjects or patients with other cardiac diseases. Left atrial reservoir function is slightly augmented in hypertensive patients even at rest, and this may at least partially play a role in the further enhancement by nifedipine administration.
Study Limitations
Two limitations of this study should be noted. First,
hemodynamic and pressure data were not available in
this study because the invasive measurements required for these data
were felt to be ethically unjustified. Therefore, we did not have any
values for invasive parameters such as the time constant of
relaxation (
) or the maximal rate of isovolumic pressure fall
[(-)dP/dt max]. Thus, the pharmacological effect of sublingual
nifedipine on LV relaxation could not be fully
investigated. However, the incomplete normalization of LV relaxation
with nifedipine administration has been well established,
and the main point of this study is not LV diastolic
function but left atrial reservoir function. Because left atrial
reservoir function is considered to be most appropriately determined by
Doppler echocardiography, additional invasive
data should not affect our conclusion.
The second limitation is the technical difficulty in obtaining adequate recordings of the pulmonary venous reverse flow wave at atrial contraction with the transthoracic approach.18 28 Given this difficulty, we did not extensively investigate the left atrial booster function by analyzing the pulmonary venous reverse flow component. However, we believe that the suboptimal recording of the reverse flow wave at atrial contraction should not invalidate the measurements of systolic and diastolic forward waves.
Clinical Implications
We have shown the importance of the left atrial reservoir function
as a contributor to the nifedipine-induced change in
the mitral flow velocity pattern in hypertensive patients. Previously,
nifedipine-induced changes in the mitral flow velocity
pattern, ie, increases in the early diastolic flow velocity
and the ratio of peak early to late diastolic flow
velocity, have been blindly interpreted as a sign of improvement of LV
diastolic function. However, our data have demonstrated
that this interpretation is inadequate because
nifedipine-induced normalization of the mitral flow
velocity pattern is associated with enhanced abnormalities of the
pulmonary venous flow velocity pattern. Thus, the normalization
of the mitral flow velocity pattern should be explained not only by the
normalized LV diastolic function but also by another
adaptive alteration in left atrial reservoir function in hypertensive
patients. The combined analysis of mitral and pulmonary
venous flow velocity patterns may be useful in avoiding the
misinterpretation of these patterns.
Received April 21, 1995; first decision June 22, 1995; accepted August 7, 1995.
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