Download Beat-to-beat analysis of pressure wave morphology for pre

Journal of the American College of Cardiology
© 2004 by the American College of Cardiology Foundation
Published by Elsevier Inc.
Vol. 44, No. 9, 2004
ISSN 0735-1097/04/$30.00
doi:10.1016/j.jacc.2004.07.046
Beat-to-Beat Analysis of Pressure Wave
Morphology for Pre-Symptomatic Detection
of Orthostatic Intolerance During Head-Up Tilt
Salvatore M. Romano, PHD, Chiara Lazzeri, MD, Marco Chiostri, MD, Gian Franco Gensini, MD,
Franco Franchi, MD
Florence, Italy
The aim of this study was to noninvasively define the hemodynamic profile characterizing the
early response to tilting.
BACKGROUND The mechanisms causing orthostatic intolerance have not been fully elucidated. Usually,
patients undergoing tilt test are studied in a time-consuming way. Moreover, the test can
cause discomfort to the patient and even be potentially hazardous.
METHODS
Nineteen orthostatic intolerant patients (OIP), compared with 22 healthy subjects (HS),
performed head-up tilt test while their arterial pressure waveform was noninvasively recorded.
We elaborated data using the Pressure Recording Analytical Method to obtain hemodynamic
parameters, then analyzing the variables by discriminant analysis.
RESULTS
Compared with HS, OIP showed lower stroke volume index (SVI) values even in baseline
conditions associated with higher values of systemic vascular resistance (SVR) and heart rate
(HR). From the third minute of the tilted position and until symptoms appeared, patients
exhibited lower values of blood pressure (BP) and SVI and higher HR values but no difference
in SVR. At termination, patients showed a further significant reduction in BP and SVI and
a persistent increase in HR.
CONCLUSIONS This investigation underlines: 1) the possibility of beat-to-beat monitoring of hemodynamic
changes during tilting; 2) the cardiovascular profile of OIP at rest, characterized by lower SVI
and higher SVR and HR; 3) the maladaptive response to postural challenge of OIP mainly
identifiable in impaired vascular regulation; and 4) the possibility of detecting parameters that
enable prompt identification of the positive response to tilting in these patients, thus guiding
the duration of the test. (J Am Coll Cardiol 2004;44:1891–97) © 2004 by the American
College of Cardiology Foundation
OBJECTIVES
We have studied patients with orthostatic intolerance (OIP) or
postural tachycardia syndrome, which is characterized by
symptoms such as lightheadedness, palpitations, fatigue,
blurred vision, dizziness, and occasionally syncope (1–3). These
symptoms usually occur after upright posture is assumed and
are associated with rapid development of tachycardia. Though
the pathophysiologic background of chronic orthostatic intolerance is still unclear, it is generally accepted that autonomic
dysfunction can be a pathogenetic hallmark of the disease and
that chronic orthostatic intolerance may constitute part of a
spectrum of disorders of orthostatic cardiovascular homeostasis, including the neuromediated syncope and perhaps the
chronic fatigue syndrome (4).
In patients with chronic orthostatic intolerance, autonomic dysfunction appears to comprise a hyperadrenergic
state during supine rest and a blunted sympathetic vasoconstrictor response of muscle blood vessels to standing, accompanied by an augmented cardiac sympathetic response
(5). Though the autonomic profile in these patients has
been extensively studied (5–7), several questions remain
unresolved, especially concerning hemodynamic response to
From the Department of Internal Medicine and Cardiology, University of
Florence, School of Medicine, Florence, Italy. Dr. Romano is the owner of the Italian
patent for the PRAM technique.
Manuscript received March 17, 2004; revised manuscript received July 26, 2004,
accepted July 29, 2004.
orthostasis. In particular, is cardiac output increased as
would be expected given the faster heart rate (HR)?
Insights into disorders of orthostatic homeostasis have
been enhanced by the advent of tilt table testing (8), which
allows simulation of standing in carefully monitored and
controlled conditions. The continuous, noninvasive measurement of blood pressure (BP) and pulse pressure wave
morphology has attained widespread use. In particular, the
Finapres device (Ohmeda, Englewood, Colorado) has provided a useful alternative for continuous intra-blood measurement in a variety of situations, including short-lasting
orthostatic stress (9 –11). Moreover, employment of the
Modelflow or Pulse Contour Method (PCM) has enabled
researchers to compute continuous noninvasive (finger)
measurements of the stroke volume in healthy subjects (HS)
(12) as well as in patients affected by chronic autonomic
failure (13). This methodology is limited by the need for
calibration (i.e. by thermodilution) to perform reliable
measures of cardiac output, able to reflect its physiologic and
pathologic variations (14). However, without calibration,
the calculation of arterial impedance and thereafter of stroke
volume can be obtained only by extrapolation, using values
referring to a previously studied population (matched for
age, gender, and anthropometric data) (14).
The aim of the present investigation is to test the usefulness
of a beat-to-beat evaluation of stroke volume and related
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Noninvasive Hemodynamics During Tilt Test
JACC Vol. 44, No. 9, 2004
November 2, 2004:1891–97
Abbreviations and Acronyms
BP
⫽ blood pressure
DBP
⫽ diastolic blood pressure
DICBP ⫽ dicrotic blood pressure
HR
⫽ heart rate
HS
⫽ healthy subjects
OIP
⫽ orthostatic intolerant patients
PCM ⫽ Pulse Contour Method
PRAM ⫽ Pressure Recording Analytical Method
SBP
⫽ systolic blood pressure
SVI
⫽ stroke volume index
SVR
⫽ systemic vascular resistance
parameters during head-up tilt test in OIP, with the aid of the
new, noninvasive, Pressure Recording Analytical Method
(PRAM). This method, different from PCM, is based on the
change of the pressure wave morphology, without any precalculated parameter or external calibration (15).
METHODS
Nineteen consecutive patients (11 males, 8 females; age 36
⫾ 17 years, range 22 to 64 years) with debilitating symptoms consistent with orthostatic intolerance and 22 HS as
controls (13 males, 9 females; age 47 ⫾ 12 years, range 20
to 72 years) gave their informed consent to participate in the
study. Patients referred to our laboratory for investigation of
symptoms of chronic orthostatic intolerance were included
in this study if they met the following criteria: 1) sustained
increase in HR of at least 30 beats/min or HR more than
120 beats/min during active standing; 2) absence of orthostatic hypotension (declines in the ratio of systolic blood
pressure [SBP] to diastolic blood pressure [DBP] during
active standing lower than 10 mm Hg); 3) duration of
symptoms longer than three successive months; and 4) daily
occurrence of at least two of the following symptoms:
palpitations, abnormal sweating, lightheadedness or dizziness, blurred vision, and presyncope or faintness sensation
during upright posture (5,16). Chronic fatigue, nausea,
vomiting, headache, and syncope were less frequent, as
previously described (16,17). Their clinical features are
presented in Table 1. In none of our patients was the onset
of symptoms attributed to earlier viral infection. No differences were observed in body surface area between patients
and control subjects (patients: 1.71 ⫾ 0.16 m2; control
Table 1. Clinical Features of Patients With Chronic Orthostatic
Intolerance (Frequency of Findings)
Symptom
Frequency
Lightheadedness
Dizziness
Palpitations
Presyncope or faintness
Syncope
Fatigue
Nausea and vomiting (while standing)
Headache (while standing)
98%
76%
75%
69%
50%
42%
42%
42%
subjects: 1.73 ⫾ 0.11 m2, p ⫽ NS). The protocol was in
accordance with the Declaration of Helsinki (1989) of the
World Medical Association and has been approved by the
ethical committee of our department.
All patients included in the study underwent a complete
medical evaluation, including electrocardiogram, 24-h
Holter recording, chest X-ray, electroencephalography,
Doppler echocardiography, complete neurologic examination, and serum blood tests (glucose, creatinine, electrolytes,
aminotransferase, ethanol, thyroid hormones, cortisol and
aldosterone, platelet count, hematocrit, red blood cell count,
white cell count), to exclude secondary causes of orthostatic
intolerance or other illnesses such as heart failure, diabetes
mellitus, neuropathy, coronary heart disease, mitral valve
prolapse, blood hypertension, and any other disease (e.g.,
adrenal insufficiency) that could affect the autonomic nervous system. The HS had no history of faintness and had
normal echocardiogram, exercise test tolerance, neurologic
and laboratory findings. Neither patients nor control individuals were taking any medication in the two weeks before
or during the study period. Patients younger than 16 years,
elite athletes, and sports professionals were excluded.
Study protocol. All subjects included in the study underwent a tilting test which was performed between 2 PM and
4 PM in a dedicated laboratory with subdued lighting and
ambient temperature of 20°C to 22°C. Subjects were required to have fasted for 4 h before tilt. They remained
supine for half an hour and were then tilted to a 60° angle
for 45 min or until they developed presyncopal or syncopal
symptoms. The motorized tilt table achieved 60° of tilt over
20 s. During the test, subjects were restrained by two Velcro
straps placed around the legs and waist, and any conversation other than reporting symptoms was discouraged.
Continuous and noninvasive beat-to-beat HR and BP
measurements were recorded. After a 30-min resting period
(equilibrium), data were obtained for a supine resting period of
2 min (baseline condition) throughout the tilted period (3 min,
5 min, and every 5 min afterwards until 45 min or symptom
appearance, and for 2 min after return to the supine position,
i.e. post tilting period). The BP measurements were achieved
by digital photoplethysmography (Finapres), a method previously described during tilt testing (18,19).
Data processing. We have, in real time, performed continuous recordings and computation of stroke volume by
PRAM of the systemic BP waves from the finger, as
described in a previous report (15,20). The computed values
of stroke volume PRAM were displayed in real time by the
dedicated software. The corresponding waves were recorded
and stored for subsequent check of the data. An event
marker on the pressure recordings was used to identify the
start of each clinical symptom.
The noninvasive pressure signals were acquired at 1,000 Hz
by means of an analogic-digital multifunction card (DAQ
Card-700; National Instruments Corp., Austin, Texas). All
the signals were recorded on a personal computer (Acer,
TravelMate 507-DX, Taipei Hsien, Taiwan, Republic of China).
JACC Vol. 44, No. 9, 2004
November 2, 2004:1891–97
Romano et al.
Noninvasive Hemodynamics During Tilt Test
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Figure 1. The behavior of systolic, diastolic, and dicrotic blood pressures as well as heart rate in healthy subjects (HS) (dashed lines) and in orthostatic
intolerant patients (OIP) (continuous lines) during head-up tilt test. *p ⬍ 0.05 HS versus OIP; #p ⬍ 0.05 in HS; §p ⬍ 0.05 in OIP.
The data from each subject were reviewed and edited
manually to remove artifacts (which consisted of the calibration intervals, devoid of pressure signal). Data from
pressure signals were evaluated averaging 1-min periods at
baseline, during up-tilting, down-tilting, the post-tilting,
and throughout the 60°-tilted position: in particular at the
3rd, 5th, 10th, 15th, 20th, and 25th (or until symptoms
supervened) minute from the up-tilted position, by averaging 30 s before and 30 s after the selected time (21).
The following parameters were calculated:
1. Heart rate (beats/min);
2. SBP, DBP, and dicrotic blood pressures (DICBP) (mm
Hg). Dicrotic pressure was computed from the second
derivative of the pressure curve in the time domain. In
fact, the dicrotic notch is the point in which the forces
generated by the blood physical properties overcome
cardiac stroke output, causing aortic valve closure.
Therefore, DICBP may approximate the left ventricular
end-systolic pressure (21,22);
3. Pulse pressure (mm Hg), as the difference between SBP
and DBP. Its peripheral amplification is a well-established
hemodynamic pattern in cardiovascular physiology (23);
4. Stroke volume index (SVI) (ml/m2);
5. Systemic vascular resistance (SVR), as mean systemic
arterial pressure/cardiac output (dynes·s·cm⫺5);
6. Ratio between stroke volume and pulse pressure (stroke
volume/pulse pressure, ml/mm Hg) as an estimate of
overall vascular compliance (24);
7. Cardiac index (ml/min/m2).
PRAM methodology. The PRAM is based on the principle
that, in any given vessel, volume changes occur mainly because
of radial expansion in response to variations in pressure. This
process involves the interplay of several physical parameters
including force of left ventricular ejection, arterial impedance
counteracting the pulsatile blood inflow, arterial compliance,
and peripheral, small vessel resistance. These variables are
tightly interdependent and simultaneously evaluated by
PRAM. Thus, any kind of flow that is perceived at the
peripheral arterial level, whether pulsatile or continuous as in
physiologic conditions, can be evaluated. A similar approach to
the pulsatile evaluation of flow has been studied by several
authors in the course of three decades and has led to the
development of clinical applications such as the PCM. Different from PRAM, however, PCM requires retrospective calibration based on independent measurements of flow and/or
pre-calculated parameters (14).
The PRAM technique, based on the analysis of the
peripheral artery waveform morphology, has been extensively described elsewhere (15). The PRAM is based on
software that analyzes the pressure signal obtained via the
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JACC Vol. 44, No. 9, 2004
November 2, 2004:1891–97
analogic card by a routine that identifies the characteristic
points of the pressure wave during each beat (diastolic,
systolic, dicrotic, and resonant points pressure during the
systolic and end-diastolic phases). The morphologic analysis
of the beat allows the determination of the stroke volume.
Statistical analysis. For statistical analysis, we used the
Statistical Package for Social Science (Version 11.5, SPSS
Inc., Chicago, Illinois). Values are expressed as mean values
⫾ 1 SD. Differences in the mean values between the two
groups were compared using an unpaired t test (p ⬍ 0.05
was considered statistically significant). Forward stepwise
discriminant analysis was used to assess: 1) the reliability of
a short-lasting test, and 2) the variables to consider in order
to predict with the best agreement the test outcome (25,26).
RESULTS
HS. All control subjects were clinically healthy and showed
no symptoms during head-tilt. As depicted in Figures 1 and
2, in comparison with baseline, up-tilting induced a slight
increase in DBP, DICBP, and HR as well as an increase in
SVR in the first 15 min of the tilted position. In the same
period, stroke volume and pulse pressure showed a progressive decline. Thereafter, the considered parameters showed
stable and still higher values throughout the tilted position,
at termination, and during down-tilting. At the end of the
test, BP values, HR, SVI, SVR, and pulse pressure were
comparable to those at the beginning.
OIP. As depicted in Figures 1 and 2, in OIP, unlike HS,
up-tilting induced within the first 3 min a sharp increase in
HR, despite the lack of changes in SBP and DBP values.
The DICBP and SVI showed a trend toward lower values.
Afterward, in the first 15 min of tilted position, OIP
showed a progressive increase in HR associated with a
progressive decrease in DICBP but with only a trend toward
lower values of SBP and DBP. Thereafter, and until
presyncopal (and rarely syncopal) symptoms supervened,
SBP, DBP, DICBP, and SVI progressively declined, SVR
manifested a trend toward a progressive decrease, whereas
HR remained at higher levels (5,13,19). In nine patients BP
reached values lower than 80 mm Hg at the end of the
procedure. Only in five patients did a true syncopal event
occur. The mean time of symptoms appearance was 17 ⫾
5.4 min from up-tilting.
In concomitance with symptoms, patients showed a
further reduction in SBP, DICBP, DBP, as well as SVI and
pulse pressure in the presence of a persistent increase in HR
and unchanged values of SVR. The down-tilting induced a
reduction in HR, a tendency to higher values of BP and
SVR, and a slight increase in SVI. At the end of the
procedure, hemodynamic parameters became comparable to
those observed at baseline. An example of the hemodynamic
profile of patients who developed syncope during head-up
tilt is depicted in Figure 3.
Comparison between HS and OIP. As shown in Table 2,
at baseline, in the resting position, OIP showed lower values
Figure 2. The behavior of stroke volume index, systemic vascular resistance, and pulse pressure in healthy subjects (HS) (dashed lines) and in
orthostatic intolerant patients (OIP) (continuous lines) during head-up
tilt test. *p ⬍ 0.05 HS versus OIP; #p ⬍ 0.05 in HS; §p ⬍ 0.05 in OIP.
of SBP, pulse pressure, and SVI, whereas they exhibited
higher values of HR and SVR. No significant differences in
stroke volume/pulse pressure ratio were found between the
two groups. During up-tilting and in comparison to HS,
OIP showed lower values of SBP, DICBP, and SVI but no
changes in SVR and stroke volume/pulse pressure.
From the third minute of tilted position and until
symptoms appeared (test termination is “Stop” in Table 2
and Fig. 2), patients exhibited lower values of SBP, DBP,
DICBP, SVI, and pulse pressure and higher values of HR
but no difference in SVR or stroke volume/pulse pressure.
At termination, patients showed a further significant reduction in BP values, pulse pressure, and SVI and a persistent
increase in HR. No significant differences between the two
groups were observed in SVR or in stroke volume/pulse
pressure ratio. At the end of the procedure, OIP showed
JACC Vol. 44, No. 9, 2004
November 2, 2004:1891–97
Figure 3. Example of the hemodynamic profile of one patient (female,
body surface area ⫽ 1.46 m2) who developed syncope during head-up tilt.
CO ⫽ cardiac output; HR ⫽ heart rate; SV ⫽ stroke volume.
lower values of SBP and SVI, without any difference in the
other variables.
Discriminant analysis. To examine whether an early termination of the head-up tilt test was feasible, we applied
forward stepwise discriminant analysis (F to enter and F to
remove, p ⫽ 0.05 and 0.10, respectively) on the entire set of
variables: first considering all time intervals up until 15 min
(DA-15) and then stopping our analysis at 3 min (DA-3),
that is, an overall number of six and three parameters,
respectively. The DA-15 found seven variables (SVI baseline, DBP-DICBP up, DICBP-DBP 3 min, SVR 3 min,
SVR 5 min, SVR 10 min, SVR 15 min), and the agreement
was approximately 95%. The DA-3 found three variables
(SVI baseline, DICBP-DBP 3 min, SVR 3 min) and total
agreement was 92%.
DISCUSSION
The main finding of the present investigation is that
individuals with orthostatic intolerance have a lower stroke
volume and higher SVR at rest than age-matched healthy
control individuals. This hemodynamic profile can be
viewed as a maladaptive response to postural challenge
Romano et al.
Noninvasive Hemodynamics During Tilt Test
1895
related to impaired vascular regulation. In this context, the
discriminant analysis allowed the identification of some
parameters (mainly SVI and SVR) able to quickly characterize the response to tilting in OIP, thus making the
prompt termination of the test feasible.
In OIP, several factors can account for the decreased SVI
in the recumbent position. The first such factor is hypovolemia, either absolute or relative, probably the result of a
different distribution of blood among the various vascular
districts and further confirmed by the higher values of SVR
and HR in patients compared with HS. The finding of
lower values of SVI throughout the whole test strongly
suggests the failure of all compensatory mechanisms physiologically involved in counteracting the hemodynamic
changes induced by posture. Our data partially disagree with
those by Furlan et al. (5), who observed that central venous
pressure was similar in the supine position and decreased by
the same extent during tilt in both OIP and control subjects.
However, in OIP, absolute values of central venous pressure
showed a trend toward lower values, though not statistically
significant. Besides, central venous pressure is an indirect
estimate of volume status (27), whereas stroke volume is a
direct measure of cardiac performance that in HS strictly
correlates with left ventricular filling as well as with afterload, myocardial contractility, and relaxation.
Secondly, deconditioning cannot be ruled out as a contributing factor to the reduced SVI. In fact, head-down tilt
bed rest causes hemodynamic effects clearly different from
those of acute hypovolemia, and in particular it induces
ventricular remodeling, leading to reduced supine left ventricular end-diastolic volume and compromised ventricular
filling (28). Deconditioning has also been suggested to
explain the marked decrease in stroke volume in response to
head-up tilt of women with chronic fatigue syndrome (29).
Finally, the reduced SVI could probably explain previously
published data by others who found that a therapeutic
strategy directed at either volume expansion with saline or
increasing peripheral vasoconstriction with the alpha1agonists midodrine or phenylepinephrine is far more effective than one directed at blunting the hyperadrenergic state
using clonidine or esmolol (7,16).
The behavior of SVR in OIP deserves some comments.
These patients showed higher values of SVR in comparison
to HS at baseline, as previously described by Stewart and
Weldon (30). However, differently from HS, SVR did not
exhibit any significant change throughout the test, despite
the postural challenge and, more importantly, despite the
higher HR (i.e., a sympathetic activation index). Bush et al.
(31) found that changes in forearm vascular resistance
(calculated as mean arterial pressure/brachial artery blood
velocity ratio) were even less in patients with postural
tachycardia syndrome during head-up tilt. Again, the lack of
increase in SVR can be viewed as the patients’ failure to face
the progressive reduction in stroke volume that follows a
decrease in venous return and strongly suggests an abnormal
regulation of vascular tone in these patients.
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JACC Vol. 44, No. 9, 2004
November 2, 2004:1891–97
Table 2. Systemic and Hemodynamic Values During the Phases of the Tilt Test Entered in the Stepwise Discriminant Analysis
SBP
(mm Hg)
DICBP
(mm Hg)
DBP
(mm Hg)
PP
(mm Hg)
HR
(beats/min)
SVI
(ml/m2)
SVR
(dyne·s·cmⴚ5)
SV/PP
(ml/mm Hg)
Base HS (n ⫽ 22)
Base OIP (n ⫽ 19)
p
126 ⫾ 16.4
115 ⫾ 15.1
⬍0.05
84 ⫾ 9.8
81 ⫾ 9.7
NS
69 ⫾ 8.6
70 ⫾ 7.9
NS
57 ⫾ 10.9
45 ⫾ 10.0
⬍0.01
72 ⫾ 10.9
80 ⫾ 12.0
⬍0.01
45 ⫾ 5.6
36 ⫾ 8.5
⬍0.01
925 ⫾ 136
1,010 ⫾ 99
⬍0.05
1.5 ⫾ 0.41
1.4 ⫾ 0.40
NS
Up HS (n ⫽ 22)
Up OIP (n ⫽ 19)
p
128 ⫾ 15.8
114 ⫾ 14.1
⬍0.01
85 ⫾ 9.1
78 ⫾ 8.7
⬍0.05
71 ⫾ 7.6
70 ⫾ 7.9
NS
56 ⫾ 11.6
45 ⫾ 10.5
⬍0.01
76 ⫾ 14.1
86 ⫾ 11.2
⬍0.05
42 ⫾ 6.6
34 ⫾ 8.4
⬍0.01
970 ⫾ 135
1,013 ⫾ 99
NS
1.4 ⫾ 0.42
1.4 ⫾ 0.53
NS
3= HS (n ⫽ 22)
3= OIP (n ⫽ 19)
p
126 ⫾ 15.6
113 ⫾ 16.2
⬍0.05
88 ⫾ 9.2
77 ⫾ 11.7
⬍0.01
75 ⫾ 7.2
71 ⫾ 11.4
NS
51 ⫾ 11.6
42 ⫾ 8.2
⬍0.01
80 ⫾ 12.8
94 ⫾ 14.9
⬍0.01
37 ⫾ 5.8
30 ⫾ 7.8
⬍0.01
1,042 ⫾ 115
1,034 ⫾ 152
NS
1.4 ⫾ 0.44
1.3 ⫾ 0.30
NS
5= HS (n ⫽ 22)
5= OIP (n ⫽ 14)
p
127 ⫾ 17.0
117 ⫾ 11.5
NS
88 ⫾ 8.9
79 ⫾ 10.8
⬍0.05
75 ⫾ 8.1
73 ⫾ 8.6
NS
52 ⫾ 12.7
43 ⫾ 7.2
⬍0.05
80 ⫾ 12.3
99 ⫾ 14.1
⬍0.01
36 ⫾ 5.8
28 ⫾ 6.1
⬍0.01
1,052 ⫾ 127
1,036 ⫾ 144
NS
1.3 ⫾ 0.45
1.2 ⫾ 0.27
NS
10= HS (n ⫽ 22)
10= OIP (n ⫽ 12)
p
125 ⫾ 15.0
114 ⫾ 13.9
⬍0.05
88.4 ⫾ 8.5
78.4 ⫾ 11.3
⬍0.01
74 ⫾ 7.2
72 ⫾ 7.9
NS
51 ⫾ 10.9
42 ⫾ 8.1
⬍0.05
80 ⫾ 11.3
101 ⫾ 14.0
⬍0.01
36 ⫾ 7.2
27 ⫾ 6.1
⬍0.01
1,066 ⫾ 127
1,042 ⫾ 171
NS
1.3 ⫾ 0.46
1.2 ⫾ 0.39
NS
15= HS (n ⫽ 22)
15= OIP (n ⫽ 19)
p
128 ⫾ 16.1
118 ⫾ 10.7
⬍0.01
89 ⫾ 8.7
72 ⫾ 8.3
⬍0.01
76 ⫾ 7.4
67 ⫾ 8.1
⬍0.01
53 ⫾ 11.9
41 ⫾ 9.4
⬍0.05
81 ⫾ 11.7
103 ⫾ 15.7
⬍0.01
36 ⫾ 6.5
27 ⫾ 7.1
⬍0.01
1,053 ⫾ 131
971 ⫾ 178
NS
1.31 ⫾ 0.42
1.30 ⫾ 0.57
NS
Down HS (n ⫽ 22)
Down OIP (n ⫽ 19)
p
127 ⫾ 16.4
106 ⫾ 20.0
⬍0.01
87 ⫾ 10.1
71 ⫾ 16.6
⬍0.01
74 ⫾ 9.2
64 ⫾ 14.0
⬍0.01
52 ⫾ 11.7
43 ⫾ 9.0
⬍0.01
79 ⫾ 11.9
91 ⫾ 16.1
⬍0.01
37 ⫾ 5.6
31 ⫾ 8.4
⬍0.01
1,040 ⫾ 127
984 ⫾ 123
NS
1.4 ⫾ 0.39
1.3 ⫾ 0.35
NS
End HS (n ⫽ 22)
End OIP (n ⫽ 19)
p
126 ⫾ 16.7
115 ⫾ 15.0
⬍0.05
86 ⫾ 11.4
79 ⫾ 10.1
NS
72 ⫾ 9.4
67 ⫾ 9.2
NS
54 ⫾ 11.4
48 ⫾ 8.6
NS
71 ⫾ 11.7
78 ⫾ 13.0
NS
44 ⫾ 7.2
39 ⫾ 8.9
⬍0.05
1,069 ⫾ 120
1,000 ⫾ 167
NS
1.5 ⫾ 0.39
1.5 ⫾ 0.48
NS
Stop HS (n ⫽ 22)
Stop OIP (n ⫽ 19)
p
128 ⫾ 13.4
103 ⫾ 16.7
⬍0.01
89 ⫾ 8.8
69 ⫾ 14.9
⬍0.01
77 ⫾ 6.6
64 ⫾ 13.3
⬍0.01
51 ⫾ 10.5
39 ⫾ 7.8
⬍0.01
81 ⫾ 11.6
97 ⫾ 16.1
⬍0.01
36 ⫾ 5.9
28 ⫾ 7.3
⬍0.01
959 ⫾ 133
973 ⫾ 138
NS
1.3 ⫾ 0.33
1.2 ⫾ 0.34
NS
DBP ⫽ diastolic blood pressure; DICBP ⫽ dicrotic blood pressure; HR ⫽ heart rate; HS ⫽ healthy subjects; n ⫽ number of patients; NS ⫽ not statistically significant; OIP
⫽ orthostatic intolerant patients; PP ⫽ pulse pressure; SBP ⫽ systolic blood pressure; SVI ⫽ stroke volume index; SVR ⫽ systemic vascular resistance; SV/PP ⫽ stroke
volume/pulse pressure ratio.
In our investigation, pulse pressure and SBP also showed a
peculiar hemodynamic profile throughout the test in OIP. In
fact, in comparison to HS, we suppose that OIP may show
lower values of pulse pressure despite an adrenergic activation
as indicated by the higher HR. On the contrary, Laurent et al.
(32) observed that the increase in HR was able to induce an
increase in pulse pressure both in HS and in hypertensive
patients. The discrepancy between our data (present investigation and Romano et al. [21]) and those by Laurent et al. (32)
strongly suggests an abnormal regulation of peripheral vascular
tone in OIP, as described in previous studies (5,30,33,34). In
fact, Stewart (33) and Jacob et al. (34) observed that patients
with orthostatic intolerance show a blunted arterial vasoconstriction which may produce passive redistribution of blood
within peripheral venous capacitance beds and accounts for
symptoms in these patients. Stewart and Weldon (30) and
Jacob et al. (34) described a decrease in norepinephrine
spillover in the lower limbs and an abnormal peripheral
vascular physiology, respectively, in idiopathic orthostatic
intolerance. Also Furlan et al. (5) described a blunted
sympathetic vasoconstrictor response to standing of muscle blood vessels in OIP as part of their selective
autonomic dysfunction.
In our findings, OIP showed lower values of SBP at rest,
and symptom appearance after prolonged tilting was associated with a further reduction in BP together with an
increased, though not compensatory, HR. This phenomenon can probably be related to the fact that our patients
were submitted to increased stimulus intensity, such as
prolonged tilt test. However, in patients with orthostatic
intolerance SBP behaves differently from hypotension to
hypertension. Indeed, whereas some patients develop symptoms in the absence of any significant BP reduction (5),
others show a trend to hypotension (4) or even a hypertensive response to standing (3). In other words, the hemodynamic response to orthostatic challenge in OIP appears to
share common characteristics both in patients with neuromediated syncope (who more frequently show a hypotensive
response) and in those with chronic fatigue syndrome (who
usually show no change in BP). It has therefore been
speculated that chronic orthostatic intolerance may constitute part of a spectrum of disorders of orthostatic cardiovascular homeostasis, including the neuromediated syncope
and chronic fatigue syndrome (4), and that postural tachycardia syndrome and neurocardiogenic presyncope or syncope both can be considered forms of dysautonomia, differ-
Romano et al.
Noninvasive Hemodynamics During Tilt Test
JACC Vol. 44, No. 9, 2004
November 2, 2004:1891–97
ing in tonic cardiac sympathetic function, with increased
cardiac norepinephrine release in the former and decreased
release in the latter (13). Thus, the diagnostic categorization
for a given patient is often mainly determined by the initial
presentation (35).
A possible limitation of the study is that enrolled patients
were selected on clinical grounds to have chronic orthostatic
intolerance. Furthermore, the possibility that some of our
patients may have inappropriate sinus tachycardia cannot be
ruled out, because these two syndromes exhibit overlapping
features and a clear distinction between the two of them is
arbitrary both in quantitative and qualitative terms (36).
In conclusion, the present study underlines the following
topics: 1) the cardiovascular profile of OIP at rest, characterized by lower SVI and higher SVR and HR; 2) the
maladaptive response to postural challenge in OIP may be
mainly identifiable in impaired peripheral arterial tone
regulation; 3) the significance of measuring SVI and SVR in
quickly identifying the positive response to tilting to optimize the timing of the test and the therapeutic strategy.
13.
14.
15.
16.
17.
18.
19.
20.
21.
Reprint requests and correspondence: Dr. Salvatore M. Romano, Department of Critical Care, School of Medicine, University of Florence, Viale Morgagni 85, I-50134 Florence, Italy.
E-mail: [email protected].
22.
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