Download Patients with a hypertensive response to exercise have

Journal of the American College of Cardiology
© 2004 by the American College of Cardiology Foundation
Published by Elsevier Inc.
Vol. 43, No. 5, 2004
ISSN 0735-1097/04/$30.00
doi:10.1016/j.jacc.2003.08.057
Stress Testing
Patients With a Hypertensive Response to
Exercise Have Impaired Systolic Function Without
Diastolic Dysfunction or Left Ventricular Hypertrophy
Philip M. Mottram, MBBS, FRACP, Brian Haluska, MS, Satoshi Yuda, MD, Rodel Leano, BS,
Thomas H. Marwick, MBBS, PHD, FACC
Brisbane, Australia
We sought to determine if a hypertensive response to exercise (HRE) is associated with
myocardial changes consistent with early hypertensive heart disease.
BACKGROUND An HRE predicts the development of chronic hypertension (HT) and may reflect a preclinical
stage of HT.
METHODS
Patients with a normal left ventricular (LV) ejection fraction and a negative stress test were
recruited into three matched groups: 41 patients (age 56 ⫾ 10 years) with HRE (⬎210/105
mm Hg in men; ⬎190/105 in women), comprising 22 patients with (HT⫹) and 19 without
resting hypertension (HT⫺); and 17 matched control subjects without HRE. Long-axis
function was determined by measurement of the strain rate (SR), peak systolic strain, and
cyclic variation (CV) of integrated backscatter in three apical views.
RESULTS
An HRE was not associated with significant differences in LV mass index. Exercise
performance and diastolic function were reduced in HRE(HT⫹) patients, but similar in
HRE(HT⫺) patients and controls. Systolic dysfunction (peak systolic strain, SR, and CV)
was significantly reduced in HRE patients (p ⬍ 0.001 for all). These reductions were equally
apparent in patients with and without a history of resting HT (p ⫽ NS) and were
independent of LV mass index and blood pressure (p ⬍ 0.01).
CONCLUSIONS An HRE is associated with subtle systolic dysfunction, even in the absence of resting HT.
These changes occur before the development of LV hypertrophy or detectable diastolic
dysfunction and likely represent early hypertensive heart disease. (J Am Coll Cardiol 2004;
43:848 –53) © 2004 by the American College of Cardiology Foundation
OBJECTIVES
A hypertensive response to exercise (HRE) is associated
with an increased incidence of chronic hypertension (HT)
during follow-up and has been proposed as a preclinical
stage of HT (1). However, it is currently unclear as to
whether HRE is associated with hypertensive end-organ
damage or other cardiovascular complications.
Early cardiovascular disease may be identified using
several new techniques, including quantitative echocardiographic parameters with strain rate (SR) imaging and
integrated backscatter (IB). Application of these recently
developed techniques to patients with HRE may allow the
detection of subtle abnormalities of myocardial function.
The aims of the study were to determine whether patients
with HRE (without resting HT) have detectable abnormalities of myocardial function and to determine the relation of
early systolic dysfunction to left ventricular (LV) hypertrophy and diastolic dysfunction in these patients.
METHODS
Patient selection. We screened 400 consecutive patients
referred for exercise electrocardiography or exercise echoFrom the University of Queensland, Brisbane, Australia. This study was supported
in part by a scholarship from the National Heart Foundation of Australia.
Manuscript received March 14, 2003; revised manuscript received August 21, 2003,
accepted August 25, 2003.
cardiography for clinical indications, mostly for investigation of chest pain syndromes. Patients with a history of
ischemic heart disease were excluded. Exercise tests were
performed using the Bruce protocol, with blood pressure
(BP) by sphygmomanometry at the end of each 3-min stage.
Entry criteria included the presence of normal regional and
global resting systolic LV function, no significant (⬎mild)
valvular dysfunction, and a negative maximum exercise
electrocardiogram or exercise echocardiogram for inducible
myocardial ischemia. A positive (HT⫹) or negative (HT⫺)
clinical history of HT was defined by elevated BP (⬎140/90
mm Hg) documented by the referring physician and treated
with antihypertensive medication. High normal blood pressure was defined as that exceeding 130/80 mm Hg. Resting
blood pressure was measured at the time of the echocardiography. A hypertensive response to maximum exercise was
defined by maximum systolic/diastolic BP ⱖ210/105 mm
Hg in males and ⱖ190/105 mm Hg in females (1,2).
Echocardiography. A detailed two-dimensional and
Doppler echocardiogram (Vivid Five, GE Vingmed, Horton, Norway) was obtained in all patients. Left ventricular
M-mode measurements of wall thickness and end-diastolic
and end-systolic diameters were used for calculation of
fractional shortening, relative wall thickness, and LV mass
(3). Left ventricular hypertrophy was defined as LV mass
JACC Vol. 43, No. 5, 2004
March 3, 2004:848–53
Abbreviations and Acronyms
Aa ⫽ late diastolic mitral annular velocity
BP ⫽ blood pressure
CV ⫽ cyclic variation
Ea
⫽ early diastolic mitral annular velocity
HRE ⫽ hypertensive response to exercise
HT ⫽ hypertension
IB
⫽ integrated backscatter
LV ⫽ left ventricle/ventricular
SR ⫽ strain rate
index ⬎116 g/m2 in males and ⬎104 g/m2 in females (4).
Comprehensive assessment of LV diastolic function included transmitral and pulmonary vein pulsed wave Doppler
imaging from the apical four-chamber view, LV color flow
propagation velocity, and mitral annular diastolic velocities
with tissue Doppler imaging. Transmitral early diastolic
velocity and deceleration time, late diastolic velocity, and
isovolumic relaxation time were recorded. Systolic and
diastolic velocities were measured in the right upper pulmonary vein, as was the velocity of the atrial reversal wave. Left
ventricular color flow propagation velocity was measured as
the slope of the first aliasing velocity of the early diastolic
signal, from the plane of the mitral valve to a point 4 cm
into the LV cavity (5). Systolic and early (Ea) and late (Aa)
diastolic velocities were measured at the medial and lateral
mitral annulus with pulsed wave tissue Doppler imaging in
the apical four-chamber view. The ratio of peak early
diastolic velocity to Ea was used to estimate LV filling
pressures (6), and the Tei index was determined as an
additional parameter of myocardial performance (7). Measurements were performed off-line and averaged from three
consecutive cardiac cycles. Satisfactory measurements were
obtained with all modalities except flow propagation velocity, which was obtainable in 57 subjects (98%).
Strain rate imaging. Three consecutive cardiac cycles of
color Doppler data were digitally recorded in each of six
walls (i.e., septum, lateral, anterior, inferior, anteroseptum,
and posterior) in three standard apical views. Strain and SR
are sensitive measures of long-axis systolic LV function that
represent dimensionless descriptions of length changes due
to the deformation of tissue caused by applied or developed
force. The rate of regional myocardial deformation (SR) was
derived from instantaneous differences in myocardial velocities within an 11-mm region of interest (8), using developmental software (TVIv61, GE Vingmed, Milwaukee,
Wisconsin). Percent deformation of the segment (myocardial strain) was obtained by integration of the SR curve.
Mean SR and peak systolic strain were calculated in each
patient by averaging the results of each wall and were
obtainable in 343 (99%) of 348 segments.
Integrated backscatter. Long-axis systolic LV function
was also assessed by cyclic variation (CV) of IB, as a means
of corroborating the SR results. Gray-scale loops of three
consecutive cardiac cycles were acquired at frame rates of 80
Mottram et al.
Exercise Hypertension and Myocardial Dysfunction
849
to 120 frames/s in three standard apical views, saved in raw
data format, and analyzed off-line (Echopac 6.1, GE Vingmed, Milwaukee, Wisconsin). The IB information in the
three cycles was averaged; then, the CV of IB during systole
was determined for each of the 16 LV segments (9) by
tracking a fixed 11 ⫻ 11 pixel region of interest in the
mid-myocardium in each frame. The magnitude of CV was
determined by the difference between the minimum and
maximum values of IB in a cardiac cycle (10). Mean CV was
calculated in each patient by averaging the results of 16
individual segments.
Calibrated IB, a measure of myocardial ultrasound reflectivity or tissue density, was obtained from the septum and
posterior wall in the parasternal view by subtracting average
pericardial IB intensity from average myocardial IB intensity (11). Measurements were obtained by adjusting the
position of the sample volume in each frame so that it was
maintained within the same region of the septum, posterior
wall, or pericardium throughout the cardiac cycle. The CV
of IB was measurable in 874 (94%) of 928 segments, and
calibrated IB in 108 (93%) of 116 segments.
Sample size and statistical analysis. Sample size calculations were based on previous data from our laboratory
comparing patients with hypertensive LV hypertrophy with
control subjects (10). These results revealed a 17% to 22%
reduction in CV of IB, SR, and peak systolic strain in
patients with hypertensive LV hypertrophy. By applying the
variance seen in these patients, a significant difference (p ⬍
0.05) of 15% between groups was predicted with a sample
size of 17 patients per group at 90% power for CV of IB and
⬎90% for SR and peak systolic strain.
Continuous variables are presented as the mean value ⫾
SD. Group differences were compared using analysis of
variance (ANOVA); post-hoc multiple group comparisons
were assessed with the Bonferroni method, adjusting for
three-way comparisons. Linear regression was used to determine correlations between continuous variables. The
relationship of strain and IB parameters with LV mass, BP,
and body weight was examined in a multiple linear regression model. Data were analyzed using standard statistical
software (SPSS version 9, Chicago, Illinois). A p value of
⬍0.05 was considered significant.
RESULTS
Clinical and exercise characteristics. Of the screened
group, 41 patients (19 HT⫺ and 22 HT⫹) demonstrated
HRE and met the entry criteria. There were no significant
age or gender differences between the HT⫺ and HT⫹
patients and the 17 age- and gender-matched control
subjects with no clinical history of HT and a normotensive
response to exercise (Table 1).
The HRE(HT⫺) patients had high normal resting BP
(mean value 136/86 mm Hg) with elevated BP at peak
exercise, but an exercise duration and maximal work load
similar to controls. The HRE(HT⫹) patients had higher
850
Mottram et al.
Exercise Hypertension and Myocardial Dysfunction
JACC Vol. 43, No. 5, 2004
March 3, 2004:848–53
Table 1. Clinical and Exercise Data
Males
Age (yrs)
Diabetes
Smoking
Hypercholesterolemia
Body mass index (kg/m2)
Exercise data
Resting mean BP (mm Hg)
Peak heart rate (beats/min)
Peak mean BP (mm Hg)
Peak systolic BP (mm Hg)
Indexed systolic BP increase (mm Hg/MET)
Exercise duration (min)
Work load (METs)
ST-segment deviation (mm)
Duke treadmill score
Control
Subjects
(n ⴝ 17)
HRE(HTⴚ)
Patients
(n ⴝ 19)
HRE(HTⴙ)
Patients
(n ⴝ 22)
6 (35%)
53 ⫾ 5
0
4
9 (53%)
24.6 ⫾ 3.1
9 (47%)
53 ⫾ 9
1
4
10 (53%)
27.7 ⫾ 4.8
9 (41%)
58 ⫾ 11
2
1
17 (77%)
29.9 ⫾ 5.6*
86 ⫾ 6
171 ⫾ 15
109 ⫾ 17
167 ⫾ 23
4.7 ⫾ 2.1
10.2 ⫾ 2.1
11.1 ⫾ 2.6
0.4 ⫾ 0.7
8.3 ⫾ 4.6
98 ⫾ 10†
164 ⫾ 16
132 ⫾ 7†
203 ⫾ 11†
8.8 ⫾ 5.9*
9.8 ⫾ 2.1
10.3 ⫾ 3.0
0.3 ⫾ 0.5
8.3 ⫾ 2.1
109 ⫾ 16†‡
159 ⫾ 20
137 ⫾ 12†
218 ⫾ 16†‡
9.4 ⫾ 3.5*
6.7 ⫾ 2.6†§
7.6 ⫾ 2.7†‡
0.2 ⫾ 0.3
5.8 ⫾ 2.8‡
p Value
(ANOVA)
NS
NS
NS
NS
NS
0.004
⬍ 0.001
NS
⬍ 0.001
⬍ 0.001
0.002
⬍ 0.001
0.001
NS
0.024
*p ⬍ 0.05 versus controls, †p ⬍ 0.001 versus controls, ‡p ⬍ 0.05 versus HRE(HT⫺) patients, and §p ⬍ 0.001 versus
HRE(HT⫺) patients; comparisons made using the Bonferroni adjustment. Data are presented as the mean value ⫾ SD or
number (%) of control subjects or patients.
ANOVA ⫽ analysis of variance; BP ⫽ blood pressure; HRE ⫽ hypertensive response to exercise; HT⫹ and HT⫺ ⫽ positive
and negative clinical history of hypertension, respectively; MET ⫽ metabolic equivalent; NS ⫽ not significant.
resting BP, higher peak systolic BP, and lower exercise
performance compared with both HRE(HT⫺) patients and
controls. The increase in systolic BP normalized for exercise
capacity was similar in both HRE groups (Table 1).
Echocardiographic findings. The HRE(HT⫺) patients
had cardiac dimensions and LV mass index similar to
control subjects (Table 2). The HRE(HT⫹) patients had
increased wall thickness and relative wall thickness but did
not have a significantly different LV mass index (p ⫽ 0.08
by ANOVA). Only 4 of the 41 patients with HRE had LV
hypertrophy, three of whom were in the HRE(HT⫹)
subgroup.
The HRE(HT⫹) patients had impaired LV diastolic
function, as evidenced by a reduced early/late diastolic
velocity ratio, prolonged deceleration time and isovolumic
relaxation time, and reduced velocities of flow propagation
and lateral Ea (Tables 2 and 3). The early/late diastolic velocity
ratio and lateral Ea velocity were less in HRE(HT⫹) than in
HRE(HT⫺) patients. The HRE(HT⫺) patients showed no
abnormalities in diastolic function (Table 3). There was no
Table 2. Two-Dimensional and Conventional Doppler Echocardiographic Data
Cardiac dimensions
LV diastolic diameter (cm)
Septal thickness (cm)
Posterior wall thickness (cm)
Relative wall thickness
Fractional shortening (%)
LV mass index (g/m2)
Left atrial area (cm2)
Transmitral Doppler imaging
Early diastolic velocity (cm/s)
Late diastolic velocity (cm/s)
Early/late diastolic velocity ratio
Early diastolic deceleration time (ms)
Isovolumic relaxation time (ms)
Pulmonary vein Doppler imaging
Peak systolic velocity (cm/s)
Peak diastolic velocity (cm/s)
Systolic/diastolic ratio
Atrial reversal velocity (cm/s)
Controls
HRE(HTⴚ)
HRE(HTⴙ)
p Value
(ANOVA)
4.89 ⫾ 0.40
0.86 ⫾ 0.09
0.86 ⫾ 0.09
0.35 ⫾ 0.03
37.9 ⫾ 7.0
79.7 ⫾ 14.0
18.4 ⫾ 3.3
5.06 ⫾ 0.44
0.95 ⫾ 0.12
0.92 ⫾ 0.14
0.37 ⫾ 0.05
40.8 ⫾ 7.3
85.4 ⫾ 16.6
20.3 ⫾ 4.2
5.01 ⫾ 0.45
0.99 ⫾ 0.14†
0.97 ⫾ 0.12*
0.39 ⫾ 0.05*
39.6 ⫾ 9.1
90.1 ⫾ 20.2
19.9 ⫾ 3.4
NS
0.005
0.023
0.043
NS
NS
NS
68 ⫾ 12
61 ⫾ 13
1.16 ⫾ 0.23
202 ⫾ 24
80 ⫾ 15
65 ⫾ 19
59 ⫾ 18
1.14 ⫾ 0.28
219 ⫾ 26
87 ⫾ 14
65 ⫾ 17
73 ⫾ 15‡
0.92 ⫾ 0.28*‡
235 ⫾ 41†
92 ⫾ 16*
NS
0.009
0.012
0.008
0.040
54 ⫾ 8
39 ⫾ 8
1.42 ⫾ 0.21
29 ⫾ 3
61 ⫾ 11
43 ⫾ 9
1.44 ⫾ 0.32
32 ⫾ 4
52 ⫾ 13
40 ⫾ 16
1.41 ⫾ 1.41
33 ⫾ 7
NS
NS
NS
0.054
*p ⬍ 0.05 versus controls, †p ⬍ 0.01 versus controls, and ‡p ⬍ 0.05 versus HRE(HT⫺); comparisons made using the Bonferroni
adjustment. Data are presented as the mean value ⫾ SD.
LV ⫽ left ventricular. Other abbreviations as in Table 1.
Mottram et al.
Exercise Hypertension and Myocardial Dysfunction
JACC Vol. 43, No. 5, 2004
March 3, 2004:848–53
851
Table 3. Tissue Doppler-Derived Mitral Annular Velocities and Flow Propagation Velocity
Septum
Ea (cm/s)
Aa (cm/s)
Ea/Aa ratio
Sa (cm/s)
Lateral wall
Ea (cm/s)
Aa (cm/s)
Ea/Aa ratio
Sa (cm/s)
Flow propagation velocity (cm/s)
Controls
HRE(HTⴚ)
HRE(HTⴙ)
p Value
(ANOVA)
10.2 ⫾ 1.3
10.7 ⫾ 1.4
0.97 ⫾ 0.13
7.9 ⫾ 0.9
10.7 ⫾ 2.0
11.1 ⫾ 2.1
0.99 ⫾ 0.22
8.0 ⫾ 1.7
9.3 ⫾ 2.3
10.4 ⫾ 2.2
0.92 ⫾ 0.29
8.0 ⫾ 2.0
0.065
NS
NS
NS
12.5 ⫾ 2.9
11.7 ⫾ 2.5
1.15 ⫾ 0.49
9.9 ⫾ 1.9
80 ⫾ 17
12.3 ⫾ 2.6
11.6 ⫾ 2.5
1.12 ⫾ 0.38
9.1 ⫾ 2.1
69 ⫾ 22
10.3 ⫾ 1.9*‡
11.2 ⫾ 2.2
0.96 ⫾ 0.28
8.8 ⫾ 1.5
57 ⫾ 20†
0.015
NS
NS
NS
0.004
*p ⬍ 0.05 versus controls, †p ⬍ 0.001 versus controls, and ‡p ⬍ 0.05 versus HRE(HT⫺); comparisons made using the
Bonferroni adjustment. Data are presented as the mean value ⫾ SD.
Aa ⫽ late diastolic mitral annular velocity; Ea ⫽ early diastolic mitral annular velocity; Sa ⫽ mitral annular systolic velocity;
other abbreviations as in Table 1.
significant difference in mitral annular peak systolic velocities
between HRE patients and control subjects.
The ratios of peak early diastolic transmitral velocity to
Ea for HRE(HT⫹) and HRE(HT⫺) patients and controls
were 7.3, 6.6, and 6.7 (p ⫽ 0.31), respectively, using septal
Ea, and 6.4, 5.9, and 5.6 (p ⫽ 0.25), respectively, using
lateral Ea. These results suggest that LV filling pressures
were normal in study patients and similar in all three groups.
Results for the Tei index were concordant with the abnormalities of diastolic function demonstrated in the
HRE(HT⫹) group (Tables 2 and 3). This parameter
increased between controls (0.409 ⫾ 0.178), HRE(HT⫺)
patients (0.504 ⫾ 0.153), and HRE(HT⫹) patients (0.603
⫾ 0.187; p ⫽ 0.004), consistent with a stepwise reduction in
myocardial performance. Post hoc testing with Bonferroni
adjustment revealed a significant difference between
HRE(HT⫹) patients and controls (p ⫽ 0.003), but the
difference between HRE(HT⫺) patients and controls was
not significant (p ⫽ 0.22).
Strain and IB. Patients with HRE had impaired long-axis
LV function, as evidenced by significantly reduced SR, peak
systolic strain, and CV of backscatter (Figs. 1 and 2). These
reductions were equally apparent in patients with and
without a history of resting HT.
In a multiple linear regression model, the lower values of
SR (p ⬍ 0.001), peak strain (p ⬍ 0.01), and CV (p ⫽ 0.01)
in HRE patients remained significant after correcting for
the effects of differences in LV mass index, systolic and
diastolic BP, and body weight. In HRE patients, there was
a trend toward a negative correlation of peak systolic strain
with diastolic BP (r ⫽ ⫺0.32, p ⫽ 0.054), but not systolic
BP (r ⫽ ⫺0.15, p ⫽ 0.38). There was no relation of BP to
either SR or CV. Thirteen of the 22 HRE(HT⫹) patients
were taking negatively inotropic agents for treatment of
HT. There was no difference in SR (p ⫽ 0.29) or peak
systolic strain (p ⫽ 0.88) between those taking and those
not taking these agents. Interestingly, CV was higher in
patients on negatively inotropic medication (6.72 vs. 5.82
dB, p ⫽ 0.02).
In contrast to the observed reductions in myocardial
systolic function, HRE patients showed no disturbances in
myocardial reflectivity (Table 4), suggesting that myocardial
density is not altered in this group.
Figure 1. Mean segmental strain rate and peak systolic strain at rest in
hypertensive response to exercise (HRE) patients with and without
hypertension (HT) and in control subjects. *p ⬍ 0.001 versus controls
using the Bonferroni adjustment.
Figure 2. Cyclic variation of integrated backscatter (IB) in hypertensive
response to exercise (HRE) patients with and without hypertension (HT)
and in control subjects. *p ⫽ 0.002 versus controls, †p ⫽ 0.001 versus
controls using the Bonferroni adjustment.
852
Mottram et al.
Exercise Hypertension and Myocardial Dysfunction
Table 4. Values of Integrated Backscatter (IB) in the Septum
and Posterior Wall, Corrected for Pericardial IB
Calibrated IB
Controls
HRE(HTⴚ)
HRE(HTⴙ)
Septum (dB)
Posterior wall (dB)
⫺21.0 ⫾ 10.3
⫺28.5 ⫾ 7.6
⫺21.5 ⫾ 6.7
⫺30.1 ⫾ 5.0
⫺19.3 ⫾ 6.9
⫺28.9 ⫾ 5.6
p ⫽ NS for all comparisons. Data are presented as the mean value ⫾ SD.
Abbreviations as in Table 1.
DISCUSSION
Although HRE patients had similar exercise capacity, cardiac dimensions, and diastolic function, compared with
control subjects with a normotensive exercise response, they
demonstrated a mild decrease in LV segmental deformation. This impairment of LV long-axis systolic function was
evident even in patients without a history of resting HT.
These results suggest that cardiac damage is evident in a
patient group that many observers would consider to be
“prehypertensive” (12).
HRE in patients without diagnosed HT. Although it is not
surprising that HRE patients with background HT (albeit
largely controlled) have mildly abnormal LV function, the
detection of abnormal function in the HT⫺ group is a
significant finding. These HRE(HT⫺) patients had high
normal (13) resting BP (mean 136/86 mm Hg), and previous
studies have demonstrated that subjects with high normal BP
have a several-fold increased risk of progression to HT during
follow-up (14) and are at increased risk of cardiovascular events
(15). Furthermore, an HRE itself is associated with the
subsequent development of HT (1). The present study underscores the importance of HRE in association with high normal
BP by demonstrating that subtle myocardial dysfunction is
already present in these patients.
Cardiac complications of early HT and HRE. LEFT
VENTRICULAR HYPERTROPHY. The lack of association between HRE and LV hypertrophy in the present study is
consistent with the results of the Framingham investigators
(2), which showed no difference in the prevalence of LV
hypertrophy in HRE after correcting for age, systolic BP,
and body mass index. Indeed, previous studies suggesting
that LV hypertrophy (rather than dysfunction) is the earliest
cardiac abnormality in both early HT (16) and HRE (17)
did not include sensitive measures of systolic and diastolic
function. Furthermore, in the present study, there was no
significant correlation of either strain or backscatter indexes
with LV mass index in HRE patients, and the reductions in
these parameters, compared with controls, remained significant after correcting for group differences in LV mass
index. Such results suggest that abnormalities of strain and
backscatter in HRE patients relate to a degree of myocardial
damage and are not explained by myocardial hypertrophy.
DIASTOLIC FUNCTION. Diastolic dysfunction is thought to
develop relatively early in the course of systemic HT, and
former clinical studies have suggested that diastolic dysfunction precedes systolic dysfunction in the progression of
hypertensive heart disease (18). In these studies, however,
JACC Vol. 43, No. 5, 2004
March 3, 2004:848–53
systolic LV function was assessed with chamber dynamics,
which do not accurately reflect myocardial systolic function
in the presence of concentric remodeling (19). In the
present study, patients at an earlier stage of HT had normal
LV structure (dimensions, mass, and calibrated IB) and
normal transmitral flow; however, despite reduced annular
diastolic velocity in only hypertensive patients with HRE,
parameters of impaired long-axis contractility were present
in all HRE patients. These findings suggest that segmental
systolic dysfunction occurs before global diastolic dysfunction and may be the earliest abnormality in hypertensive
heart disease. However, they do not exclude the presence of
segmental diastolic dysfunction in this group, as diastolic
SR imaging was not performed.
SYSTOLIC DYSFUNCTION. Although overt systolic dysfunction is associated with advanced hypertensive heart disease,
animal studies have demonstrated impaired velocity of
myocardial contraction in the presence of hypertensive
hypertrophy (20). Similarly, despite the presence of a
normal ejection fraction in patients with hypertensive LV
hypertrophy, human studies have shown reduced mid-wall
shortening (21), which is an independent predictor of
cardiac death in hypertensive patients (22). The present
study extends these findings by demonstrating impaired
systolic LV function in both hypertensive patients with
minimal increases in LV mass and HRE patients with
normal LV mass and normal global diastolic function.
A recent study of hypertensive patients with concentric
remodeling found that fractional shortening and systolic
mitral annular velocities were decreased in the long axis, but
not in the short axis, as compared with controls (23). These
results suggest that impairment of long-axis systolic function may occur before changes in radial contractile function
in hypertensive heart disease and are consistent with reduced long-axis strain and IB parameters demonstrated in
patients without concentric remodeling in the present study.
Mechanism of LV dysfunction in HRE. The mechanism
of subtle systolic dysfunction in HRE patients is unclear.
Although it may reflect periodic surges in BP related to
exertion and possibly emotional stress, in the majority of
patients, BP only reached excessive levels at or near peak
exercise and was in the normal range at work loads reflective
of normal daily activities. We therefore suspect that myocardial dysfunction developed after long-term exposure to
high normal levels of BP.
Although we believe that reductions in SR and backscatter parameters in HRE patients reflect intrinsic myocardial
damage, an alternative explanation might invoke the presence of increased afterload. However, several lines of evidence refute the suggestion that afterload differences are
responsible for our results. First, previous work in patients
with hypertensive LV hypertrophy has shown that afterload
is not a determinant of shortening in the long-axis plane
(21). Second, previous work with systolic myocardial velocity (the local gradient of which is used to generate SR
Mottram et al.
Exercise Hypertension and Myocardial Dysfunction
JACC Vol. 43, No. 5, 2004
March 3, 2004:848–53
curves) showed this was relatively independent of hemodynamic factors (24). Third, the strain results are independently supported by CV of IB, which is relatively independent of load (25). Finally, there was no significant
relationship between BP and long-axis systolic function in
the present study; indeed, despite a progressive increment in
resting mean BP in control subjects and HRE(HT⫺) and
HRE(HT⫹) patients, strain and CV parameters were
reduced equally in both of the HRE groups. Thus, although
SR is unlikely to be entirely independent of afterload, the
effects at physiologic loads are likely to be small.
Clinical implications. As our understanding of the risk of
end-organ damage due to HT has evolved, guidelines for
target BP in hypertensive patients have periodically been
revised downward. The present study adds further support
to this trend by identifying impaired myocardial function in
patients with high to normal resting BP who exhibit HRE.
These changes may represent the earliest cardiac abnormality in hypertensive heart disease and may identify patients at
risk of developing clinical heart failure.
The findings suggest that SR imaging and CV of IB are
promising quantitative techniques for noninvasive myocardial characterization, which may aid in the early detection of
hypertensive heart disease. More importantly, they may
allow monitoring of the response to treatment interventions
with greater sensitivity than, for example, serial measurement of LV dimensions with M-mode imaging. Important
questions to be addressed include whether the observed
systolic dysfunction is reversible with effective treatment of
HT, and what is the relation of decreased CV and strain
parameters to clinical risk?
Reprint requests and correspondence: Prof. Thomas H. Marwick, Department of Medicine, University of Queensland, Princess Alexandra Hospital, Ipswich Road, Brisbane Q4102, Australia. E-mail: [email protected].
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