Vol. 279, Issue 1, H122-H129, July 2000
Short-term variability of pulse pressure and systolic and
diastolic time in heart transplant recipients
Denis
Chemla,
Eduardo
Aptecar,
Jean-Louis
Hébert,
Catherine
Coirault,
Daniel
Loisance,
Yves
Lecarpentier, and
Alain
Nitenberg
Service de Physiologie et d'Explorations Fonctionnelles and
Institut National de la Santé et de la Recherche Médicale
(INSERM) U251, Centre Hospitalier Universitaire (CHU) Xavier Bichat,
Assistance Publique-Hôpitaux de Paris, 75018 Paris; Service de
Chirurgie Thoracique et Cardiovasculaire, CHU Henri Mondor, 94 010 Créteil; Service d'Explorations Fonctionnelles Cardiovasculaires
et Respiratoires, CHU de Bicêtre, 94 275 Le Kremlin-Bicêtre
Cedex; and INSERM U451, Loa-Ensta-Ecole Polytechnique, 91 761 Palaiseau
Cedex, France
 |
ABSTRACT |
In heart
transplant recipients (HTR), short-term systolic blood pressure
variability is preserved, whereas heart rate variability is almost
abolished. Heart period is the sum of left ventricular ejection time
(LVET) and diastolic time (DT). In the present time-domain prospective
study, we tested the hypothesis that short-term fluctuations in aortic
pulse pressure (PP) in HTR were related to fluctuations in LVET.
Seventeen male HTR (age 48 ± 6 yr) were studied 16 ± 11 mo
after transplantation. Aortic root pressure was obtained over a 15-s
period using a micromanometer both at rest (n = 17) and
following the cold pressor test (CPT, n = 14). There
was a strong positive linear relationship between beat-to-beat LVET and
beat-to-beat PP in all patients at rest and in 13 of 14 patients following CPT (each P < 0.01). The slope of this
relationship showed little scatter both at rest (0.34 ± 0.07 mmHg/ms) and following CPT (0.35 ± 0.09 mmHg/ms,
P = not significant). Given the essentially fixed heart
period, DT varied inversely with LVET. As a result, in 13 of 17 HTR at
rest and in 12 of 14 HTR following CPT, there was a negative linear
relationship between beat-to-beat PP and DT. In conclusion, our
short-term time-domain study demonstrated a strong positive linear
relationship between LVET and blood pressure variability in male HTR.
We also identified a subgroup of HTR in whom there was a mismatch
between PP and DT.
diastole; transplantation; blood pressure; stress; heart rate
| |
INTRODUCTION |
IN HUMAN HEART TRANSPLANT
RECIPIENTS (HTR), the vagally mediated component of respiratory
sinus arrhythmia is absent, resulting in a markedly reduced heart rate
variability (3, 33, 35). Conversely, the respiratory variations of systolic blood pressure are
preserved, and it is thus widely accepted that short-term heart period
fluctuations are not mandatory for the maintenance of normal short-term
fluctuations of blood pressure (20, 25, 43). Because systolic aortic pressure (SAoP)
reflects the combined influence of diastolic aortic pressure (DAoP) and
aortic pulse pressure (PP), PP is expected to give a more accurate
reflection of pulsatile pressure changes than does SAoP.
PP is mainly determined by stroke volume and total arterial compliance
(10, 39). The most widely accepted hypothesis
is that short-term fluctuations in PP in HTR are mainly of mechanical origin and reflect respiratory-related changes in stroke volume. Such
fluctuations affect PP (13, 20,
34, 41) without the confounding effects of
respiratory sinus arrhythmia and baroreflex feedback on heart period
and aortic pressures (12, 22,
40-43).
At first glance, blood pressure variability and variability in time
intervals may appear to be completely unrelated in HTR. However, one
must keep in mind that heart period is the sum of left ventricular
ejection time (LVET) and diastolic time (DT) (6,
46). A precise evaluation of beat-to-beat changes in LVET
and DT in HTR remains to be documented, as well as the potential link
between time-interval variability and blood pressure variability. Given
that LVET is strongly related to heart period (5,
6, 15, 23, 46), one
might expect the variability of LVET to be markedly decreased in HTR
and to be dissociated from the preserved blood pressure variability. On
the other hand, heart period is only one of many factors that affect
LVET, including loading conditions and inotropic state, and therefore
LVET may not necessarily follow heart period in HTR. Given that
increased preload tends to prolong ejection duration (5,
8, 23, 38), one might expect
blood pressure variability in HTR to be related to beat-to-beat LVET via a common hemodynamic mechanism, namely, the respiratory-related changes in preload. Thus the first aim of the present time-domain study
was to document short-term fluctuations in LVET in HTR and their
potential link with beat-to-beat PP. To study a wide pressure range,
data were obtained at baseline and following the cold pressor test
(CPT) (18, 29).
In HTR, where beat-to-beat fluctuations in DT are concerned, DT is
expected to vary inversely with LVET because mathematically the two
must add up to the same number (fixed heart period). Decreased DT
limits subendocardial perfusion in various pathophysiological settings
relevant to coronary heart diseases (6, 15,
16, 26), especially when coronary
vasodilation is maximal and coronary pressure is reduced
(9, 21, 30), or in cases where
arterial load is increased (15, 19).
Diastolic abnormalities have also been reported at the early stages of
rejection (14) and contribute to the decreased tolerance
of exercise (28, 31) and afterload challenge
(36) in HTR. It therefore seems important to document DT
in HTR, both at rest and during CPT, and this was the second aim of our study.
| |
METHODS |
Patients.
Seventeen consecutive male heart transplant recipients were enrolled in
our prospective study. All patients gave informed consent, and the
ethical committee of our institution approved the protocol. Patients
were referred for routine evaluation of heart transplant. Coronary
arteries were angiographically normal. Right ventricular endomyocardial
biopsies performed the day of the investigation did not evidence any
signs of rejection. Posttransplantation immunosuppressive therapy
included prednisone and cyclosporin for all 17 patients and
azathioprine for 8 of these 17. Fourteen patients were given
antihypertensive therapy. They were given 
-adrenergic blocking
agents (n = 8), 
-adrenergic blocking agents (n = 9), angiotensin-converting enzyme inhibitors
(n = 1), or diuretics (n = 3).
Vasoactive drugs were discontinued 24 h before the investigation.
Patients were considered normotensive at the time of the investigation,
when SAoP was <140 mmHg (n = 9). There were three
untreated patients and six patients whose arterial pressure was
normally controlled with antihypertensive therapy. The patients whose
SAoP was insufficiently controlled despite antihypertensive therapy
were considered hypertensive at the time of the investigation
(n = 8). The characteristics of the study population
are listed in Table 1.
Catheterization technique and protocol.
Patients were studied according to our routine protocol
(1, 11, 27). All patients were
in the fasting state for at least 12 h before the investigation.
No premedication was administered. Lidocaine (1%) was used for local
anesthesia, and 5,000 units of heparin were administered intravenously.
The left heart pigtail catheter was an 8-F single-lumen catheter with a
lateral high-fidelity transducer (Cordis/Sentron, Roden, The
Netherlands). The percutaneous femoral approach was used: the catheter
was advanced from the femoral artery to the aortic root. Right heart
catheterization was performed with a thermodilution catheter (Edwards
Laboratories) using the femoral vein approach, and cardiac output was
determined (average of 3 consecutive measurements) using the
thermodilution technique (Cardiac Output Computer model 9520 A, Edwards
Laboratories). After a 5-min equilibrium period, pressure data were
recorded at baseline over a 15-s period. The catheter was then advanced into the left ventricle, and the left ventricular angiography was
performed. After the catheter was withdrawn into the aortic root, and
following a 10-min equilibrium period, the CPT was performed (n = 14) by immersing the patient's hands in ice water for
120 s. Pressure data were then recorded over a 15-s period. The
CPT was not performed in three patients for technical reasons.
Throughout the protocol, the patient was asked to breath normally. The
data were computed on a Toshiba 3,200 SX with customized software
(sampling rate: 1,000 Hz). During computation, care was taken not to
include premature ventricular beats in the overall 15-s pressure runs under study. A coronary angiography and right ventricular
endomyocardial biopsy were performed following CPT.
High-fidelity recordings at the aortic root level and cardiac
output.
SAoP and DAoP were measured automatically, and PP was calculated
(PP = SAoP 
DAoP). Mean aortic pressure was calculated as the total area under the pressure curve divided by heart
period. Our high-precision (1 ms) analysis enabled subtle
beat-to-beat changes in time intervals to be measured. Heart period was
measured as the time between two consecutive aortic pressure upstrokes. LVET was measured from the foot of the pressure upstroke to the trough
of the incisura. As previously recommended (15,
16), DT was calculated as T minus LVET, where
T is heart period. The intra- and interobserver
reproducibility of time-interval measurements was 99% and 97%
respectively. Heart rate-corrected LVET (LVETc) was calculated using
the standard formula (46). Heart rate-corrected DT (DTc)
was calculated as T minus LVETc. We also calculated the systolic pressure-time index (SPTI) and the diastolic pressure-time index (DPTI), i.e., the pressure-time integral during systole and
diastole, respectively. The DPTI-to-SPTI ratio (DPTI/SPTI) was also
calculated, given that this ratio has been proposed as a reliable index
of subendocardial perfusion (7, 9,
19). Stroke volume (SV) was calculated by dividing cardiac
output by heart rate.
Data analysis and statistics.
Pressure values and time parameters were averaged out over the 15-s
period under study. Results are expressed as means ± SD. We
investigated whether changes in DT and LVET from one beat to the next
were in phase (i.e., both time intervals increased or both decreased)
or out of phase (i.e., one time interval increased while the other
decreased). Furthermore, individual relationships were sought between
beat-to-beat changes in aortic pressure and the spontaneous
fluctuations in heart period, LVET, and DT. Linear regressions were
performed using the least-squares method. Coefficients of variation
(CV) were calculated as SD/mean. Comparisons between normotensive and hypertensive HTR at baseline were performed using Student's unpaired t-test after analysis of variance. The
effects of CPT were studied using Student's paired t-test
following analysis of variance. A P value <0.05 was
considered statistically significant.
| |
RESULTS |
Systolic time and diastolic time at rest.
A strong relationship was found between heart period and DT
(n = 17; r = 0.96, P < 0.001) (Fig. 1A). Both SAoP
and PP were linearly related to LVET (r = 0.73 and
0.76 respectively, each P < 0.01), but not to heart
period (r = 0.26 and 0.43, respectively) or DT
(r = 0.04 and 0.23, respectively). Heart period was
similar in normotensive and hypertensive HTR. Compared with their
rate-corrected values, LVET was prolonged and DT was shortened in
hypertensive HTR (Table 2).
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Fig. 1.
Relationship between heart period and diastolic time (DT;
 ) and left ventricular ejection time (LVET;  )
in the male heart transplant recipients (HTR) at baseline
(A; n = 17) and following the cold pressor
test (CPT) (B, n = 14).
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Both the increased aortic pressure and the prolonged LVET resulted in a
markedly higher SPTI (~35%) in hypertensive than in normotensive HTR
(Table 2). The DPTI was moderately higher (~20%) in hypertensive HTR
than in normotensive subjects. The proportionally greater increases in
SPTI compared with DPTI resulted in a lower DPTI/SPTI in hypertensive
HTR compared with normotensive subjects (Table 2).
Beat-to-beat fluctuations of time intervals at rest.
Over the 15-s period under study, 20 ± 2 consecutive beats were
analyzed (range: 16-23 beats). Beat-to-beat fluctuations in time
intervals (calculated as CV; n = 17) were 0.7 ± 0.2, 2.4 ± 1.1, and 1.3 ± 0.4% for heart period, LVET, and
DT, respectively. In 13 of 17 patients, in >50% of the beats
under study (69 ± 11%, range: 55-89%), spontaneous changes
in LVET and DT were out of phase, i.e., one time interval increased
while the other decreased. In these patients, given that heart period
was essentially fixed, DT fluctuations from one beat to the next were
therefore about equal in magnitude and opposite in sign in comparison
with LVET fluctuations. In the remaining 4 of the 17 patients, LVET and DT were out of phase in 50% (n = 3) and 45%
(n = 1) of the beats.
Beat-to-beat relationship between time intervals and aortic
pressure at rest.
In all patients, there was a strong positive linear relationship
between beat-to-beat LVET and beat-to-beat PP (n = 17, each P < 0.001 except in 1 of 17 HTR, where
P < 0.01) (Table 3).
Similar results were observed when SAoP was considered instead of PP, although the correlation was weaker (Table 3). The slope of the PP-LVET
relationship showed little scatter among patients (means ± SD;
0.34 ± 0.07 mmHg/ms; n = 17) (Fig.
2). There was a negative relationship
between beat-to-beat PP and beat-to-beat DT in 13 of 17 patients
(P < 0.05 to P < 0.001) (Table 3). A
typical example is shown in Fig.
3B. This finding was explained
by both the positive relationship between beat-to-beat PP and LVET and
the virtually fixed beat-to-beat heart period. Thus the higher the
beat-to-beat pulsatile stress, the shorter the beat-to-beat diastolic
duration in these patients. As expected, no systematic relationship was found between beat-to-beat SAoP and beat-to-beat heart period (Table
3). Finally, there was no difference between normotensive and
hypertensive patients with regard to the CV of PP, DT, LVET, and heart
period.
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Table 3.
Correlation between beat-to-beat PP and beat-to-beat time intervals and
between beat-to-beat SAoP and beat-to-beat time intervals at baseline
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Fig. 2.
Individual relationships at baseline between LVET and
aortic pulse pressure in HTR (n = 17). Note that the
slope of this relationship shows little scatter among patients. Data
were analyzed over a continuous, 15-s period (20 ± 2 consecutive
beats). Each patient is represented by a different symbol.
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Fig. 3.
Typical beat-to-beat relationships between time intervals
and aortic pulse pressure at baseline () and following
CPT () in 1 patient. A: strong positive relationship
between LVET and aortic pulse pressure at baseline (r = 0.96, P < 0.001) and following CPT (r = 0.95, P < 0.001). Note the upward shift in this
relationship following CPT. B: strong negative relationship
between DT and aortic pulse pressure at baseline (r = 0.92, P < 0.001) and following CPT
(r = 0.90, P < 0.001). C:
weak relationship between heart period and aortic pulse pressure at
baseline (r = 0.63, P < 0.01) and lack
of relationship between heart period and aortic pulse pressure
following CPT (r = 0.08, P = not
significant).
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Effects of CPT on time intervals.
The effects of CPT are summarized in Table
4 (n = 14). Heart period
was related to DT (r = 0.93, P < 0.001) and LVET (r = 0.66, P < 0.05)
(Fig. 1B). Compared with baseline values, heart period
decreased while LVET increased, resulting in disproportionate decreases
in DT. After CPT, the shortened DT compensated for the increases in
aortic pressure such that DPTI remained unchanged. Conversely, both the
increased aortic pressure and increased LVET resulted in an increased
SPTI (P < 0.001) and thus a lower DPTI/SPTI (P < 0.001) (Table 4).
Over the 15-s study period, 20 ± 2 consecutive beats were
analyzed (range: 15-22 beats). After CPT, beat-to-beat
fluctuations in time intervals (calculated as CV; n = 14) were 0.9 ± 0.5% [P = not significant (NS)
vs. baseline], 2.6 ± 1.4% (P = NS vs.
baseline), and 2.1 ± 1.3% (P < 0.05 vs.
baseline) for heart period, LVET, and DT, respectively. In 11 of 14 patients, in >50% of the beats under study (71 ± 13%,
range: 55-93%), spontaneous changes in LVET and DT were out of
phase. In the remaining 3 of the 14 patients, LVET and DT were out of
phase in only 42, 47, and 48% of the beats, respectively.
Effects of CPT on the beat-to-beat relationship between aortic
pressure and time intervals.
No systematic relationship was found between beat-to-beat PP and
beat-to-beat heart period (n = 14). Conversely, in 13 of 14 patients, a strong positive relationship was found between beat-to-beat LVET and beat-to-beat PP (r ranging from 0.65 to 0.98, each P < 0.001). Similar overall results were
observed when systolic aortic pressure was considered instead of PP,
although the correlation was weaker. The slope of the PP-LVET
relationship showed little scatter among patients (0.35 ± 0.09 mmHg/ms, n = 14; P = NS vs. baseline)
(Fig. 4). CPT induced a parallel, upward shift in this relationship such that beat-to-beat PP increased whatever
the LVET. A typical example is given in Fig. 3A. The negative relationship between beat-to-beat PP and beat-to-beat DT
previously documented at baseline was still found in 12 of the 14 patients (P < 0.05 to P < 0.001) such
that the higher the pulsatile stress, the shorter the DT (Fig.
3B).
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Fig. 4.
Individual relationships between LVET and aortic pulse
pressure in HTR following CPT. Note that the slope of this relationship
shows little scatter among patients. Data were analyzed over a
continuous, 15-s period (20 ± 2 consecutive beats). Each patient
is represented by a different symbol.
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DISCUSSION |
The present study showed that, in male HTR, there was a strong
linear relationship between beat-to-beat LVET and beat-to-beat aortic
PP in the absence of heart period variability. Similar results were
obtained at baseline and following CPT, and the slopes of the various
PP-LVET relationships showed very little scatter. Short-term recordings
(15 s) were studied in the time domain, so it was essentially
respiratory-related changes in arterial pressure that were analyzed.
The present observation links cardiac hemodynamics with blood pressure
variability in HTR and is consistent with the major role of
respiratory-related changes in stroke volume in aortic pressure
variability in HTR. In clinical settings associated with chronic
(hypertensive HTR) or acute (CPT) increases in aortic pressure, we
documented a mismatch between increased arterial load and unchanged or
decreased DT, and this contributed to the lower DPTI/SPTI. We also
identified a subgroup of HTR in whom the higher the beat-to-beat PP,
the shorter the beat-to-beat DT. The decreased DT together with
increased arterial load might be considered a deleterious hemodynamic
pattern where graft perfusion is concerned.
Relationship between beat-to-beat LVET and PP.
In spontaneously breathing subjects, short-term fluctuations in blood
pressure mainly reflect the respiratory-related changes in stroke
volume, thus leading to inspiratory decreases and expiratory increases
in blood pressure (41). In HTR, respiratory variations of
systolic pressure are preserved, whereas heart rate variability is
markedly reduced. Previous studies performed in healthy subjects or in
patients with various forms of cardiac diseases have shown that both
chronic and acute increases (or decreases) in stroke volume are
associated with increases (or decreases) in LVET (5, 8, 23, 38). Although a
cause-and-effect relationship cannot be proved in the present study,
beat-to-beat changes in LVET could reflect respiratory-related changes
in stroke volume, which would affect PP (13,
20, 34, 41), without the
confounding effects of respiratory sinus arrhythmia and baroreflex
feedback on heart period and aortic pressures (12,
22, 40-43). This hypothesis is
reinforced by our finding that LVET was very closely related to PP.
Indeed, numerous studies have suggested that beat-to-beat PP reflects
the respiratory-related changes in stroke volume more accurately than
does beat-to-beat SAoP (13, 20,
34). Because PP is mainly determined by stroke volume and
total arterial compliance (10, 39), the role
of arterial compliance needs to be discussed. Respiratory-related
changes in intrathoracic pressure may modify aortic compliance and thus
PP. Conversely, sympathetic mediated changes in aortic compliance are
unlikely to be involved in our short-term results because compliance
fluctuates slowly with fluctuations in sympathetic tone. Finally,
beat-to-beat changes in the extent of wave reflection may also
contribute to the relationship between LVET and PP (19), a
point that deserves further study.
Numerous mechanisms tend to prolong or shorten LVET, so other
explanations cannot be excluded. Changes in the speed at which stroke
volume is ejected are unlikely to be involved in the PP-LVET relationship, because faster ejection rates are associated with increased PP but decreased LVET (5). Although the
low-frequency harmonic spectral power in systolic blood pressure is
significantly decreased in HTR (20), we cannot exclude the
possibility that primary increases in peripheral arterial tone
contribute to SAoP increases, thus leading to prolonged LVET
(37). However, this mechanism is likely to play a minor
role in our results given that only short-term recordings were analyzed.
The increase in aortic pressure following CPT was associated with a
decrease in heart period, a paradoxical lengthening of LVET, and, thus,
a disproportionate decrease in DT. This could be explained by the
inability of the denervated, grafted heart to respond adequately to
inotropic and chronotropic stimulation by shortening electromechanical
systole (17, 24), therefore unmasking the
prominent influence of increased preload on LVET. Similarly, in
reducing the effects of catecholamines on the myocardium, -blockade
has been shown to induce a disproportionate lengthening of LVET during
exercise and, thus, a shorter diastolic time, in hypertensive patients
(16). Shaver et al. (37) also reported that
LVET lengthens when arterial pressure is elevated (through metoxamine
infusion), whereas heart rate is held constant by atrial pacing.
As observed in patients at rest, a strong positive relationship between
short-term variability of LVET and aortic PP was also found in all
patients following CPT. The slopes of the various PP-LVET relationships
showed very little scatter in both cases. This point remains to be
explained. The CPT causes an elevation in mean arterial pressure and
total peripheral resistance via increased sympathetic vasomotor control
(18, 29). It can therefore be said that acute
changes in arterial pressure, total peripheral resistance, and
sympathetic drive did not appear to modify the slope of the
relationship between LVET and aortic PP variability.
DT in HTR.
The duration of LV subendocardial wall perfusion is mainly dependent on
DT (9, 21). Decreased DT limits
subendocardial perfusion in various pathophysiological settings
relevant to coronary heart diseases, especially in cases where arterial
load is increased (15, 19, 21).
In HTR, a close linear relationship between heart period and DT was
found at rest, indicating that heart period was the main determinant of
DT (Fig. 1). This close relationship is consistent with previous
findings in normal subjects and in patients with various forms of
cardiac diseases (6, 15, 16,
26). When heart period was taken into account, the HTR
whose systolic aortic pressure was <140 mmHg had a normal DT, whereas
hypertensive HTR had a decreased DT. This finding was explained by both
the similar heart period in the two subgroups and the prolonged LVET in
hypertensive versus normotensive HTR.
Our results also indicated that unchanged or decreased DT together with
increased arterial load contributed to the imbalance between myocardial
O2 supply and demand in hypertensive HTR and in all HTR
during CPT (Table 4). DT may well play a critical role in coronary
perfusion abnormalities in HTR whose hypertension is insufficiently
controlled by medical therapy and in all HTR during stress.
We observed small beat-to-beat fluctuations in DT in HTR, whereas heart
rate variability was almost abolished. The most likely explanation is
that HTR start with a fixed heart period (lack of autonomic modulation
of the sinoatrial node) and, because LVET fluctuates (probably
subsequent to fluctuations in stroke volume), DT necessarily varies
inversely with LVET because mathematically the two must add up to the
same number. Primary changes in DT may also play a role, albeit minor,
in light of the suggestion by Bernardi et al. (4) that
spontaneous changes in DT may adapt to changes in LV filling in the
absence of autonomic modulation of heart rate in HTR. In 13 of 17 HTR
at rest and in 12 of 14 HTR following CPT, beat-to-beat analysis
indicated that the longer the duration of LV ejection, the higher the
aortic PP and the shorter the DT. This may lead to cyclic mismatch
between arterial load and the subendocardial perfusion duration in
normal daily life.
Implications.
Our results are consistent with the mechanical role of
respiratory-related changes in stroke volume in PP variability.
Furthermore, mean power of the ejecting left ventricle critically
depends on the duration of LV ejection. Thus the strong relationship
observed between LVET and PP suggests a powerful link between LV
energetics and blood pressure variability in HTR. The implications of
our results in terms of the variability of the ventricular-arterial coupled system have yet to be studied.
The long-term survival of human transplant recipients is compromised by
cardiac allograft vasculopathy, i.e., an accelerated graft coronary
artery disease that is essentially immune mediated (44).
Coronary perfusion may be also impaired by hemodynamic factors limiting
subendocardial perfusion. Overall, decreased DT together with increased
arterial load might be considered a deleterious hemodynamic pattern
where graft perfusion is concerned.
During stress, it has been suggested that a decrease in diastolic
perfusion time could not be balanced by a proportional increase in
coronary blood flow in cases where there is failure to achieve maximal
coronary vasodilation (15). This is likely to occur in HTR
with fixed coronary artery stenosis or in HTR soon after grafting, in
whom the CPT fails to dilate epicardial coronary arteries
(2). After acute elevation of LV afterload (e.g., exercise), increased filling pressure and decreased ejection
performance have been reported in HTR. These changes have been linked
to several factors, including inadequate heart rate response
(31), decreased isovolumic relaxation rate
(28), and a decreased preload reserve (36).
The disproportionate decrease in DT may also play a part in increasing
filling pressure, a point that deserves further study.
Study limitations.
One of the limitations of our study is that only male patients were
analyzed. Further study is needed to confirm our findings in female
HTR. DT is shorter in healthy women than in men at any heart rate level
(5, 23, 46). The shorter DT
contributes to the lower DPTI/SPTI consistently observed in healthy
women >50 yr of age compared with men (19). Given the
higher mortality in women undergoing heart transplantation, it might be
important to incorporate heart rate and DT in the risk factors used in
univariate and multivariate analyses of survival (45).
A second limitation is that only short-term recordings (15 s) were
analyzed in the time domain, so only the respiratory-related changes in
arterial pressure were covered. A third limitation is that recent
studies have reported that, in some experimental conditions, a
reduction in DT was not necessarily associated with changes in
myocardial perfusion (32) and that there was a substantive systolic component in nutritive myocardial perfusion. These findings call into question the validity of time intervals for assessing O2 supply and demand. A fourth limitation is that neither
respiration nor beat-to-beat stroke volume were monitored in our study,
so further study is needed to confirm our hypotheses. A fifth
limitation is that the study was not controlled, so the specific
influences of both intact autonomic control of heart rate and
hypertension on the PP-LVET relationship remain to be investigated.
In summary, a positive linear relationship was found between
beat-to-beat LVET and aortic PP in male HTR in the absence of heart
period variability. The slope of the PP-LVET regression lines showed
very little scatter both at baseline and following CPT. This finding
demonstrates a strong link between cardiac hemodynamics and blood
pressure variability in HTR and is consistent with the major role of
respiratory-related changes in stroke volume in PP variability. On
average, in men with grafted hearts, DT was mainly related to heart
period. In hypertensive HTR at rest and in all patients during CPT,
prolonged LVET and unchanged or shortened DT contributed to the lower
DPTI/SPTI. We also identified a subgroup of HTR in whom there was a
continuous beat-to-beat mismatch between DT and PP at rest. Overall,
the hemodynamic pattern of decreased DT together with increased
arterial load may be considered deleterious from the viewpoint of graft perfusion.
| |
ACKNOWLEDGEMENTS |
We thank the nurses from the Service de Physiologie et
d'Explorations Fonctionnelles, Hôpital Bichat. We also thank
Sheila Carrodus for helpful discussions.
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FOOTNOTES |
This study was funded in part by grants from Assistance
Publique-Hôpitaux de Paris (PHRC AOM96174).
Address for reprint requests and other correspondence:
D. Chemla, INSERM U451-Loa-Ensta-Ecole Polytechnique, Batterie de
l'Yvette, 91 761 Palaiseau, France (E-mail:
chemla{at}enstay.ensta.fr).
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Received 12 May 1999; accepted in final form 3 January 2000.
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