Download Pulse Wave Analysis of the Aortic Pressure Waveform in Severe Left

Pulse Wave Analysis of the Aortic Pressure Waveform in
Severe Left Ventricular Systolic Dysfunction
Scott J. Denardo, MD; Ramavathi Nandyala, MD; Gregory L. Freeman, MD;
Gary L. Pierce, PhD; Wilmer W. Nichols, PhD
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Background—The effect of moderate left ventricular systolic dysfunction (LVSD) on ventricular/vascular coupling and the
aortic pressure waveform (AoPW) has been well described, but the effect of severe LVSD has not.
Methods and Results—We used noninvasive, high-fidelity tonometry of the radial artery and a mathematical transfer
function to generate the AoPW in 25 treated patients with LVSD (mean LV ejection fraction, 24⫾8.8%; range, 11% to
40%; 21 patients ⬍30%). Pulse wave analysis of the AoPW was used to characterize ventricular/vascular coupling and
compared with pulse wave analysis performed in 25 normal subjects matched for age, gender, height, body mass index,
and heart rate. Measurements obtained using pulse wave analysis in LVSD patients indicated features of poor LV stroke
performance and also reduced indices of arterial stiffness: increased travel time of the pressure wave (147⫾10 ms versus
132⫾21 ms; P⬍0.001); decreased systolic duration of reflected wave (134⫾24 ms versus 167⫾26 ms; P⬍0.001);
ejection duration (277⫾22 ms versus 299⫾25 ms; P⬍0.008); percent systolic duration (32⫾5.3% versus 35⫾4.0%;
P⬍0.02); aortic systolic pressure (100⫾16 mm Hg versus 121⫾16 mm Hg; P⬍0.001); unaugmented pressure
(24⫾6.3 mm Hg versus 32⫾6.4 mm Hg; P⬍0.001); augmented pressure (4.8⫾3.1 mm Hg versus 9.6⫾4.5 mm Hg;
P⬍0.001); pulse pressure (28⫾7.4 mm Hg versus 42⫾9.5 mm Hg; P⬍0.001); augmentation index (12⫾6.6% versus
23⫾7.6%; P⬍0.006); wasted LV effort (5.3⫾2.8⫻102 dyne sec/cm2 versus 17⫾10⫻102 dyne sec/cm2; P⬍0.001);
systolic pressure time index (17⫾4.1⫻102 mm Hg-sec/min versus 23⫾4.2⫻102 mm Hg sec/min; P⬍0.001); and
pressure systolic area (383⫾121 mm Hg sec/min versus 666⫾150 mm Hg sec/min; P⬍0.001).
Conclusions—Severe LVSD causes measurable changes in the AoPW. Standardization of AoPW findings in LVSD
patients may allow for the clinical use of radial artery pulse wave analysis to noninvasively determine the severity of
dysfunction and aid in logical therapy. (Circ Heart Fail. 2010;3:149-156.)
Key Words: aortic pressure waveform 䡲 left ventricular dysfunction 䡲 hemodynamics 䡲 ventricular/vascular coupling
T
he measured central aortic pressure waveform (AoPW) is
the summation of a forward-traveling (incident) wave
generated by left ventricular (LV) ejection and a backwardtraveling wave caused by reflection of the forward wave from
sites of change in impedance within the peripheral arterial
system.1–3 Both the forward and reflected pressure waves are
related to LV ejection wave amplitude. Additionally, the
forward traveling wave is affected by central (elastic) arterial
stiffness and peak LV ejection, whereas the reflected wave is
affected by the elastic properties of the entire arterial tree,
transmission velocity of the forward and reflected waves, and
distance to the major reflecting site. The functions of the LV
and peripheral arterial system are interactive (ie, ventricular/
vascular coupling) and conditions that directly affect one can
cause a responsive change in the other.4 The net effect of this
coupling on the morphology of the AoPW can be described
by a series of quantifiable characteristics obtained using pulse
wave analysis (PWA).5–7 Certain clinical conditions, such as
advanced age, obesity, hypertension, diabetes mellitus, coronary artery disease, myocardial infarction, and chronic renal
disease unfavorably alter ventricular/vascular coupling, and
the associated changes in the AoPW have been described.8 –12
Additionally, this unfavorable alteration of ventricular/vascular coupling is associated with increased arterial stiffness and
has been linked directly to the subsequent development of
adverse cardiovascular outcomes including chronic heart
failure and death.
Clinical Perspective on p 156
Central aortic pulse pressure (cPP)—the difference between the central aortic systolic and diastolic blood pressure—is a characteristic of the AoPW that is relatively simple
to measure. Recent studies have shown that both invasive13
and noninvasive14,15 measurements of cPP correlate positively and strongly with the subsequent development of
cardiovascular disease and adverse outcomes. Conversely, 3
Received March 10, 2009; accepted October 10, 2009.
From the University of Florida (S.J.D., W.W.N.) and Department of Veterans Affairs Medical Center (S.J.D.), Gainesville, Fla; University of Texas
Health Science Center (R.N., G.L.F.), San Antonio, Tex; and University of Colorado (G.L.P.), Boulder, Colo.
Correspondence to Scott J Denardo, MD, Division of Cardiovascular Medicine, University of Florida College of Medicine, 1600 SW Archer Rd, PO
Box 100277, Gainesville, FL 32610. E-mail [email protected]
© 2010 American Heart Association, Inc.
Circ Heart Fail is available at http://circheartfailure.ahajournals.org
149
DOI: 10.1161/CIRCHEARTFAILURE.109.862383
150
Circ Heart Fail
January 2010
taking cardiovascular drugs at the time of the study. All patients and
subjects had data collected in the basal state, in the supine position,
and in a quiet, temperature-controlled room after a rest period of at
least 10 minutes.
Peripheral Cuff Blood Pressure Measurement
Brachial systolic and diastolic blood pressures (bSP and bDP,
respectively) were measured in the left arm using a validated,
automatic, oscillometric BP monitor (Omron R3, Omron Healthcare,
Kyoto, Japan), and an appropriately sized cuff. Three measurements
were taken at least 2 minutes apart and the latter 2 were averaged and
used in data analysis and calibration of the AoPW. The variable bPP
was calculated as the difference between bSP and bDP.
Pulse Waveform Analysis
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Figure 1. A synthesized central aortic pressure waveform. The
early part of the ascending aortic pressure wave of amplitude
(Pi⫺Pd) is generated by LV ejection. The later part of the pressure wave with amplitude (Ps⫺Pi) is generated by the reflected
wave arriving during systole and adding to the forward pressure
wave. cPP⫽(Pi⫺Pd)⫹(Ps⫺Pi)⫽(Ps⫺Pd) and AIa⫽(Ps⫺Pi)/(Ps⫺Pd).
The area under the systolic portion of the reflected wave (dark
shaded area) is defined as LV wasted effort (Ew). PSA⫽⌬PSA⫹Ew
and is the area enclosed by the systolic pulse pressure wave.
SPTI⫽⌬SPTI⫹⌬PSA⫹Ew and is the area under the systolic portion
of the pressure wave and DPTI is the area under the diastolic portion of the wave. P1 indicates the first systolic pressure peak (or
shoulder); Pi, merging point (inflection point) of the forward and
reflected waves; Tr, round-trip travel time of the pressure wave;
SDR, systolic duration of reflected wave; ED, ejection duration.
previous large clinical studies found an inverse (or negative)
relation between peripheral brachial pulse pressure (bPP) and
mortality in patients with severe LV systolic dysfunction
(LVSD).16 –18 Additionally, the effects of mild to moderate
LVSD on arterial stiffness and the AoPW in patients with
normal mean arterial pressure have been fairly well described
and show an increase in aortic stiffness, pulse wave velocity
(PWV), characteristic impedance, and cPP compared with
normal subjects.19 –23 However, a quantitative description of
the AoPW in patients with severe LVSD beyond cPP has not
been fully described. We therefore sought to investigate
changes in the AoPW associated with altered ventricular/
vascular coupling in patients with severe LVSD using noninvasive, high-fidelity tonometry of the radial artery and
synthesized central aortic PWA.
Methods
LVSD Patient and Normal Subject Populations
This cross sectional study was approved by the University of Florida
Institutional Review Board, and all LVSD patients (N⫽25) and
normal subjects gave informed written consent. Twenty-three of the
LVSD patients had New York Heart Association Class III to IV
chronic congestive heart failure symptoms. Additionally, all LVSD
patients were in normal sinus rhythm; all had undergone quantitative
echocardiography which confirmed LVSD as the cause of heart
failure (LV ejection fraction [EF] range, 11% to 40%; 21 patients
⬍30%) and demonstrated no significant valvular abnormality, and
all were receiving medical therapy accordingly. Data from these 25
LVSD patients were compared with those from a group of normal
subjects (N⫽25) matched for age, gender, height, body mass index,
and heart rate. Normal subjects were all asymptomatic, had no
history of cardiovascular disease, and had normal clinical examinations and normal ECGs. None of them were current smokers or
Assessment of wave reflection characteristics, ejection duration, and
area indices were performed using the SphygmoCor system (AtCor
Medical, Sydney, Australia). Radial artery pressure waveforms,
calibrated using cuff measured brachial systolic and diastolic pressure, were recorded at the left wrist noninvasively, using applanation
tonometry that incorporated a high-fidelity micromanometer (Millar
Instruments, Houston, Tex). A validated generalized mathematical
transfer function was applied to 20 sequential waveforms, which
were then ensemble averaged to generate the central AoPW (Figure 1).24
Characteristics of the AoPW were then determined using PWA.5,6,25
Importantly, the time from the beginning upstroke of the synthesized
aortic systolic pressure waveform (Pd) to the upstroke of the reflected
wave (inflection point, Pi) is the round-trip travel time (Tr) of the
pressure wave to and from the major reflecting site in the lower body
and is related to arterial stiffness of the entire arterial system.2,4,7
Increased arterial stiffness increases PWV and leads to a more rapid
Table 1. Baseline Characteristics of LVSD Patients and
Normal Subjects
LVSD Patients
(N⫽25)
Normal Subjects
(N⫽25)
P
Age, y
57⫾11
54⫾11
0.43
Male gender
20 (80)
20 (80)
1.00
173⫾9.5
174⫾7.4
0.62
Characteristic
Height, cm
Weight, kg
2
85⫾18.6
82⫾16.8
0.58
Body mass index, kg/m
29⫾6.1
27⫾3.9
0.08
Heart rate, bpm
69⫾13
72⫾11
0.51
NYHA CHF class III/IV
23 (92)
0
LVEF, %
24⫾8.8
NA
CAD
10 (40)
0
CABG
9 (36)
0
17 (68)
0
ACE-I
15 (60)
0
ARB
3 (12)
0
␤-blocker
6 (24)
0
␣␤-blocker
13 (52)
0
Diuretic
18 (72)
0
ALD-blocker
9 (36)
0
Digoxin
6 (24)
0
Risk Conditions
ICD
Medication, %
Data are presented as mean⫾SD or n (%). NYHA indicates New York Heart
Association; NA, not available; CAD, coronary artery disease; CABG, coronary
artery bypass grafting; ICD, intracardiac defibrillator; ACE-I, angiotensin
converting enzyme inhibitor; ARB, angiotension receptor blocker; ALD,
aldosterone.
Denardo et al
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return of the reflected wave from the periphery to the heart, a shorter
Tr, and a longer systolic duration of the reflected wave (SDR).4,7
Aortic augmentation index (AIa), a measure of wave reflection
intensity, can be estimated as the ratio of wave reflection amplitude
(Ps⫺Pi) and cPP (Ps⫺Pd). When the reflected wave returns during
systole as a result of increased PWV and/or decreased reflection site
distance, as seen in Figure 1, the aortic pressure is augmented in late
systole, and, therefore, the LV must generate enough effort to
overcome this augmentation in pressure and opposition to emptying
during flow deceleration.4 This pressure effort, which takes into
account both amplitude and SDR, is wasted (ie, wasted effort, Ew)
because it does not contribute to blood flow production and can be
estimated as the area under the systolic portion of the reflected
wave.26 Ew is that portion of the systolic pressure time index
(SPTI) resulting from wave reflection and is directly related to
LV hypertrophy.26 The SPTI is directly related to myocardial
oxygen demand and is estimated as the area under the systolic
portion of the aortic pressure wave above zero.27 The pressure
systolic area (PSA) is the area under the systolic portion of the
aortic pressure wave above diastolic pressure. When Ew is small
or zero, PSA is directly related to stroke volume and is dependent
AoPW and LV Systolic Dysfunction
151
on ejection duration and cPP. Diastolic pressure time index
(DPTI) is an estimate of coronary artery perfusion pressure and is
related to coronary blood flow and is estimated as the area under
the diastolic portion of the pressure wave. The ratio of DPTI/SPTI
represents the ratio of myocardial supply and demand and is
termed the myocardial viability ratio.28 The ratio of bPP and cPP
is the pressure pulse amplification, and it increases as arterial
stiffness and wave reflection amplitude decrease and vice versa.4
Only high-quality recordings, defined as an in-device quality
index of ⬎80% (derived from an algorithm including average pulse
height, pulse height variation, diastolic variation, and the maximum
rate of rise of the peripheral waveform) and acceptable curves on
visual inspection, were included in the analysis.
Statistical Analysis
Data for continuous variables are presented as mean⫾SD. Comparisons between individual hemodynamic variables obtained from the
2 matched groups were made using a paired 2-tailed Student t test.
Comparisons within the LVSD patients were made using an unpaired
2-tailed Student t test. Statistical significance was assumed when
probability values were ⬍0.05.
Figure 2. Illustration showing the alterations in noninvasively measured radial artery and synthesized aortic pressure waves in a patient
with heart failure and severe LVSD (lower panel) compared to a normal subject (upper panel) with similar heart rate, height and age.
Ejection duration (270 versus 322 ms), percent systolic duration (31 versus 36%), unaugmented pressure (21 versus 29 mm Hg), augmented pressure (1.0 versus 13 mm Hg), and AIa are reduced in the heart failure patient resulting in diminished wasted LV effort
(96 versus 1887 dyne sec/cm2), SPTI (1880 versus 2355 mm Hg sec/min) and PSA (301 versus 627 mm Hg sec/min). In this example, mean arterial pressure was similar between the two (96 versus 98 mm Hg) while both peripheral (36 versus 50 mm Hg) and
central (22 versus 41 mm Hg) pulse pressures were less in the heart failure patient. Pi is the inflection point and denotes the
beginning upstroke of the reflected wave. The radial artery pressure wave of the heart failure patient displays a dicrotic wave
while the aortic pressure wave does not.
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Circ Heart Fail
January 2010
Statement of Responsibility
The authors had full access to the data and take responsibility for its
integrity. All authors have read and agree to the manuscript as
written.
Results
Patients and Subjects
The LVSD patients and normal subjects were well matched
with regard to age, gender, height, body mass index, and heart
rate (Table 1). The mean EF for the 25 LVSD patients was
24⫾8.8% (range, 11% to 40%; 21 patients ⬍30% and 4
patients ⱖ30%). Additionally, the LVSD patients had multiple risk conditions, and they were on multiple medications
oriented toward the management of severe LVSD.
Table 2. Measured and Calculated Variables for LVSD Patients
and Normal Subjects
Variable
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All measured and calculated variables for the normal subjects
were similar to those previously published for other normal
subjects.29 An example of the radial artery pressure wave and
the synthesized central AoPW obtained in a normal subject
and a LVSD patient is shown in Figure 2. The measured bSP
and bDP were each significantly less in LVSD patients
compared with normal subjects (Table 2), as was the calculated bPP. Additionally, the measured central systolic blood
pressure, central mean pressure, cPP, and calculated unaugmented pressure (ie, forward wave amplitude [Pi⫺Pd]) were
each less in LVSD patients. Also, ejection duration (Figure
3), percent systolic duration, and PSA were each less in the
LVSD patients. However, pulse pressure amplification was
greater in the LVSD patients compared with normal subjects.
Amplitude and Timing of Wave Reflection Indices
The amplitude (augmented pressure) and systolic duration
(SDR) of the reflected pressure wave were both less in the
LVSD patients compared with the normal subjects (Table 2;
Figure 3). Additionally, Tr of the pressure wave to and from
the periphery was greater. This delay in return of the reflected
wave to the heart indicates a decrease in PWV and/or an
increase in reflection site distance. These differences in wave
reflection characteristics produced a lower AIa and suggest a
decrease in wave reflection intensity and arterial stiffness in
the LVSD patients. This contention is also supported by the
increase in pulse pressure amplification.
Indices of Myocardial Oxygen Demand
The observed differences in arterial wall properties and wave
reflection characteristics indicate a significant reduction in
pulsatile LV afterload. These afterload changes were associated with a decrease in indices of myocardial oxygen demand.
The decrease in wave reflection amplitude and duration in the
LVSD patients caused a decrease in Ew (Table 2; Figure 3).
Also, the decreased central systolic blood pressure and
abbreviated ejection duration in LVSD patients caused a
decrease in the cross product (heart rate⫻central systolic
blood pressure) and estimated SPTI compared with the
normal subjects. Finally, DPTI was decreased in the LVSD
patients. These area changes in systole and diastole caused an
increase in the myocardial viability ratio.
Normal
Subjects
(N⫽25)
P
bSP, mm Hg
111⫾17
134⫾18
⬍0.001
bDP, mm Hg
71⫾13
78⫾10
⬍0.04
bPP, mm Hg
40⫾9.5
56⫾11
⬍0.001
cSP, mm Hg
100⫾16
121⫾16
⬍0.001
cMP, mm Hg
83⫾14
98⫾12
⬍0.001
cPP, mm Hg
28⫾7.4
42⫾9.5
⬍0.001
Unaugmented
pressure, mm Hg
24⫾6.3
32⫾6.4
⬍0.001
277⫾22
299⫾25
⬍0.002
32⫾5.3
35⫾4.0
⬍0.02
PSA, mm Hg-sec/min
383⫾121
666⫾150
⬍0.001
Augmented
pressure, mm Hg
4.8⫾3.1
9.6⫾4.5
⬍0.001
SDR, ms
134⫾24
167⫾26
⬍0.001
Tr, ms
147⫾10
132⫾21
⬍0.001
AIa, %
12⫾6.6
23⫾7.6
⬍0.006
Pulse pressure
amplification
(dimensionless)
1.5⫾0.11
1.4⫾0.09
⬍0.008
17⫾10⫻102
⬍0.001
87⫾19⫻102
⬍0.002
Ejection duration, ms
Components of Peripheral Brachial and Central
Aortic Blood Pressure
LVSD Patients
(N⫽25)
Percent systolic
duration, %
Ew, dyne-sec/cm2
5.3⫾2.8⫻102
2
Cross Product
关HR⫻cSP], mm Hg/min
69⫾17⫻10
SPTI, mm Hg sec/min
17⫾4.1⫻102
23⫾4.2⫻102
⬍0.001
DPTI, mm Hg sec/min
2
32⫾6.0⫻10
35⫾4.6⫻102
⬍0.03
1.9⫾0.52
1.6⫾0.27
⬍0.002
DPTI/SPTI
(dimensionless)
b indicates brachial; c, central; SP, systolic pressure; DP, diastolic pressure;
PP, pulse pressure; MP, mean pressure; unaugmented pressure, (Pi⫺Pd);
augmented pressure, (Ps⫺Pi); SDR, systolic duration of reflected wave; Tr,
round-trip travel time of the pressure wave; AIa, augmentation index; Ew,
wasted effort; HR, heart rate; SPTI, systolic pressure time index; DPTI, diastolic
pressure time index; DPTI/SPTI, myocardial viability ratio.
Intragroup Comparison of LVSD Patients Based
on LVEF
Among the LVSD patients, those with LVEF ⱕ20% (N⫽11)
compared with those with LVEF ⬎20% (N⫽14) primarily
contributed to the decrease in percent systolic duration (29⫾
4.6% versus 34⫾5.6%; P⬍0.04), PSA (348⫾86 mm Hg sec/
min versus 429⫾126 mm Hg sec/min; P⬍0.02), and SPTI
(1484⫾232 mm Hg sec/min versus 1924⫾428 mm Hg sec/
min; P⬍0.01). Otherwise, the data from these 2 subgroups
appeared similar.
Discussion
The results of this study indicate that PWA of the AoPW,
determined using noninvasive, high-fidelity tonometry of the
radial artery, can describe the effects of severe LVSD and
altered arterial properties on ventricular/vascular coupling in
the time domain. In this description, there was a decrease in
all components of both central and peripheral blood pressure
Denardo et al
AoPW and LV Systolic Dysfunction
153
Figure 3. Bar graphs showing average values
in normal subjects (light bars) and patients with
severe LVSD (dark bars) of ejection duration
(299⫾25 versus 278⫾21 ms), reflected wave
amplitude (9.6⫾4.5 versus 3.7⫾2.4 mm Hg),
SPTI (2335⫾418 versus 1731⫾414 mm Hg
sec/min), and wasted LV pressure effort
(1680⫾1021 versus 534⫾380 dyne sec/cm2).
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(systolic, diastolic, pulse, and mean) compared with normal
subjects. Similar observations for peripheral blood pressure
have been made in this population by others, and a low bPP
has been found to be independently associated with increased
mortality.16 –18
Earlier studies, including the Systolic Hypertension in the
Elderly (SHEP) and Survival and Ventricular Enlargement
(SAVE) studies, found that increased conduit artery stiffness,
as assessed by bPP, may contribute to increased adverse
outcomes in patients with LV dysfunction.30 –32 These studies,
however, only measured the extremes in brachial blood
pressure (ie, bPP⫽bSP⫺bDP), whereas in our study, the
central AoPW, a more accurate indicator of LV afterload and
adverse outcome, was measured. Several other studies have
measured central AoPW, but most of those studies were
performed in patients with mild-to-moderate LVSD (LVEF
30% to ⬎40%),20,22,23,33–35 whereas our study was performed
primarily in patients with severe LVSD (21 of 25). Most of
the earlier studies found no change in aortic PWV and travel
time of the pressure wave to and from the periphery.
However, in contrast to those results, we found an increase in
Tr of the pressure wave, indicating a decrease in PWV, and an
increase in pulse pressure amplification, which together
imply a decrease in arterial stiffness and is consistent with the
measured decrease in augmented pressure and AIa. Our
results are supported by the results of Tartière et al,33 which
involved patients with a similar EF (mean LVEF 24⫾9%
among study patients with reduced EF) and which showed a
decrease in the effects of wave reflection on AoPW. These
pressure changes result from altered ventricular/vascular
coupling. In systolic heart failure, when ventricular contractility is severely impaired, wave reflection does not boost late
systolic pressure because the LV is incapable of responding
adequately, so that systole is terminated prematurely, and
wave reflection has a negative influence on the flow wave
during deceleration and in heart failure shortens ejection
duration.36
Additional novel characteristics of the AoPW in severe
LVSD shown in this study include decreased unaugmented
pressure, ejection duration, SDR, percent systolic duration
and indices of myocardial oxygen demand, and LV function
including unaugmented pressure, PSA, Ew, cross product, and
SPTI.
Most previous studies performed in patients with mild to
moderate heart failure (LVEF 30% to ⬎40%) showed an
increase or no change in arterial stiffness. Only one previous
study reported a decrease in arterial stiffness and PWV
similar to our findings; this was the study by Tartière et al,33
performed in patients with severe LVSD and reduced mean
arterial pressure. Because the activities of the LV and
peripheral arterial system are interactive (ventricular/vascular
coupling), the decrease in arterial stiffness and PWV may be
the result of a decrease in mean arterial pressure in response
to reduced cardiac output and LV afterload. This decreased
arterial stiffness and wave reflection— essentially, a decrease
in impedance—is partly because of the effect of arterial
vasodilating drugs and a decrease in mean arterial pressure
which is probably just a marker of severe LV dysfunction. In
both the Tartière et al33 study and this study, a majority of the
LVSD patients received either angiotensin converting enzyme inhibiting or angiotension receptor blocking drugs,
which decrease peripheral arterial stiffness directly (actively)
and central arterial stiffness indirectly (passively).
The measured decreases in systolic unaugmented pressure,
Ew, and SPTI shown in this study are the result of a decrease
in LV contractile function and consequent inability to generate force and pressure to overcome the augmented pressure
associated with the severe LVSD resulting in reduced stroke
volume and PSA. The decrease in SPTI and cross product
indicate a consequent decrease in LV oxygen requirements,
and the increase in DPTI/SPTI indicates an increase in
myocardial viability ratio. This may serve as a compensatory
mechanism in severe LVSD to optimize efficiency of the
failing LV.
Morphological changes in the pressure wave contour in
systolic heart failure were reported well over a hundred years
ago. Flemming suggested in 1881 that the necessary conditions for the presence of 2 distinct upstrokes in the peripheral
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January 2010
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Figure 4. Illustration showing changes in the AoPW that occur during the development and progression of LVSD. A, Young normal
healthy subject with reflected wave occurring predominately in diastole; ejection duration (broken line) is 316 ms, cPP is 26 mm Hg,
SPTI is 2047 mm Hg sec/min and PSA is 440 mm Hg sec/min. B, During aging and develop of hypertension the reflected wave (amplitude 23 mm Hg in this example) occurs almost entirely in systole resulting in an increase in AIa, wasted effort, cPP (59 mm Hg), SPTI
(3206 mm Hg sec/min) and PSA (802 mm Hg sec/min) causing LV hypertrophy which begins the process of systolic heart failure. C, As
heart failure proceeds reflected wave amplitude (7 mm Hg), AIa, cPP, ejection duration (269 ms), SPTI (2196 mm Hg sec/min), and PSA
(558 mm Hg sec/min) begin to decrease. D, In LVSD, the augmented systolic pressure and wasted effort become almost zero, LV ejection is shortened further (235 ms) which causes a reduction in SPTI (1535 mm Hg sec/min), percent systolic duration (28%) and PSA
(361 mm Hg sec/min).
pulse wave often seen in heart failure included a fast pulse,
elastic vessels, feeble tension in the vessels, and a small
amount of blood injected with each ventricular systole.37 A
few years later, Lewis38 described a characteristic dicrotic
(twice-beating) pulse, which is typical in patients with LVSD
resulting from cardiogenic shock after myocardial infarction,3,4,39 after open heart surgery40 and in cardiomyopathy.41,42 Such morphological changes in pulse contour with
LVSD are confined to the peripheral pulse and are seldom
seen in the AoPW.43 Fifty-six percent of the patients in our
study displayed a dicrotic wave in the radial pulse (Figure 2).
An explanation for the progression from normal LV
systolic function to severe LVSD is available on the basis of
the argument proposed by Westerhof and O’Rourke36 and
Nichols and O’Rourke.4 This explanation has been effectively
used to characterize mechanical pumps, with the LV seen to
act as a flow source (powerful ejection) in youth when the
ventricle is optimally matched to a compliant arterial system
and power generation is minimal. Under these circumstances,
stroke volume is directly related to PSA and the reflected
wave arrives in diastole (Figure 4A) and aids in coronary
artery perfusion. The age-related increase in elastic artery
stiffness (and PWV) causes the reflected wave to arrive
earlier to the heart and boost pressure in late systole that
places an extra pulsatile workload on the LV causing it to
generate more force, which is wasted effort. These changes in
arterial properties and wave reflection characteristics cause
the LV to change from a flow source to a combined flow and
pressure source (ejection limited by pressure achieved) as
hypertension develops (Figure 4B). As the elastic arteries
become stiffer, the LV becomes primarily a pressure source
and the myocardial oxygen demand is greater. Sustained
elevation and prolongation of late systolic augmentation
results in LV hypertrophy,26,44,45 which is associated with
progressive degenerative changes in the myocytes such that
these weaken and develop less force with each contraction.
The weakened, hypertrophied fibers lengthen and the LV
dilates, with augmented systolic pressure and stroke output
initially being maintained (Figure 4C) at greater muscle
length and LV volume through the Frank-Starling mechanism.3,4 The LVEF in these patients is usually ⱕ40%.
Ultimately, compensation is lost and the LV cannot generate
the extra force necessary to completely overcome the late
systolic augmented pressure. Augmented pressure, AIa, and
Denardo et al
systolic (and pulse) pressure are therefore reduced and
associated with a decrease in ejection duration, Ew, PSA,
SPTI, and stroke volume. The LVEF in these patients is
usually ⬍30%.33 When LV contractility is severely impaired,
wave reflection does not boost systolic pressure (Figure 4C)
because the heart is incapable of responding, so that systole is
terminated prematurely, and wave reflection is seen to have
had a negative influence on flow rather than a positive
influence on pressure3,33 and the LV reverts back to a flow
source (weak and abbreviated ejection) as heart failure
progresses (Figure 4D). Again there is a direct positive
relation between stroke volume and PSA; therefore, an
improvement in hemodynamics will be viewed as an increase
in ejection duration, augmented pressure, pulse pressure, and
PSA.9
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Limitations
This study has one principal limitation. The radial artery
pressure waveforms were calibrated using cuff measured
brachial systolic and diastolic pressure. However, this method
of calibration may result in an overestimation of the central
aortic pressures.46,47 Nonetheless, this overestimation should
be a systematic error and affect all results proportionately.
Conclusions
PWA of the AoPW may provide more detailed and accurate
information into the severity of LV dysfunction compared
with the measures of brachial pulsatility. This information
may prove vital in the diagnosis and risk stratification of
patients with LV dysfunction, especially when severe, and yet
may be performed accurately in the outpatient clinic setting.
Further standardization of AoPW findings in LVSD patients
may allow for the clinical use of arterial PWA to noninvasively characterize reduced LV systolic performance, including severe LVSD and aid in logical therapy.
Disclosures
Dr Nichols is a consultant for AtCor Medical (Sydney, Australia).
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CLINICAL PERSPECTIVE
The effect of moderate left ventricular systolic dysfunction on ventricular/vascular coupling and the aortic pressure
waveform has been well described, but the effect of severe left ventricular systolic dysfunction has not. This research shows
that severe left ventricular systolic dysfunction causes measurable changes in the aortic pressure waveform, as determined
using noninvasive, high-fidelity tonometry of the radial artery and a mathematical transfer function. Standardization of
aortic pressure waveform findings in left ventricular systolic dysfunction patients may allow for the clinical use of radial
artery pulse wave analysis to noninvasively determine the severity of dysfunction and aid in logical therapy.
Pulse Wave Analysis of the Aortic Pressure Waveform in Severe Left Ventricular Systolic
Dysfunction
Scott J. Denardo, Ramavathi Nandyala, Gregory L. Freeman, Gary L. Pierce and Wilmer W.
Nichols
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Circ Heart Fail. 2010;3:149-156; originally published online November 10, 2009;
doi: 10.1161/CIRCHEARTFAILURE.109.862383
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