Discussion:
To our knowledge, this is the first study to describe the patient
characteristics, clinical and echocardiographic predictors and
implications of hypertensive dobutamine response in ESRD patients. In
the present study, prevalence of hypertensive response was found to be
21% which is strikingly higher than general population, described
previously as around 1-7% (3, 9-11).
The major determinant of this abrupt and marked elevation in BP during
stress test in ESRD patients appears to be their pre-stress BP of
>160 mm Hg. whereas a pre-stress SBP of <140
appears to have protective effect against hypertensive response. Because
of high prevalence of LVH and left atrial dilatation in hypertensive
response patients, this pre-stress uncontrolled BP appears to be a
chronic phenomenon. Higher left atrial pressure despite similar right
atrial pressures in patients with hypertensive response suggest possible
contribution from excess volume on a back-drop of other abnormalities
generally encountered in ESRD patients such heightened sympathetic
nervous system activity (12-13), decreased renal clearance and elevated
vascular vasoconstrictor endothelin 1 levels (14), hyperactivity of
Renin Angiotensin system (15-16) that would increase plasma renin
activity and angiotensin II levels, decreased nitric oxide levels (17)
and pathological changes in the arterial system including reduced
compliance, medial hypertrophy and vascular calcification (18-22).
Before DSE in ESRD populations, it may be prudent to bring systolic
blood pressure <140 mmHg and get them euvolumic to reduce the
probability of a hypertensive response. LV hypertrophy has also been
shown to elicit a hypertensive response to stress (23). Greater use of
angiotensin converting enzyme inhibitor or receptor blocker in the group
with hypertensive response is likely a marker for need for greater
number of antihypertensive agents to control the blood pressure. The
strong relationship between pre-stress elevated BP and elevated post
stress elevation shown in our study is in accordance with prior studies
of hypertensive response with dobutamine (9-11) as well as with exercise
stress testing in general population (24).
Reliability of dobutamine echocardiogram to detect significant CAD
defined as > 70% luminal narrowing of an epicardial
coronary artery was lower in our ESRD population compared with general
population (25-27), with similar performances in both normotensive group
and hypertensive groups. It is possible that the definition of
significant CAD may not apply to ESRD patients who have heavily
calcified coronary arteries and increased myocardial mass which would
affect both supply and demand for oxygenated blood. The high false
positive rates may possibly be due to underestimation of coronary
stenosis because of complex pathology in ESRD, transient stress induced
cardiomyopathies from dobutamine (28), just an afterload mismatch in
those with a hypertensive response or microvascular disease. Low
sensitivity to detect significant CAD is a concern as well. It is
possible that a hyperdynamic response to dobutamine in a hypertrophied
LV may markedly reduce end systolic wall stress (as radius to wall
thickness ratio is low) and may result in false negative testing.
Hyperdynamic response with LV cavity obliteration was very common in our
subjects. LV cavity obliteration with DSE has been associated with false
negative DSE results (28).
Neither the hypertensive response nor stress induced wall motion
abnormalities in the hypertensive group was associated with reduced
survival during the limited follow-up. But stress induced wall motion
abnormalities predicted reduced survival in the normotensive group. The
latter findings are not surprising but have important practical
implications as neither the extent of CAD nor coronary calcium burden
were predictors of survival in our ESRD cohort. Hence, DSE in the
normotensive group seems to be a better prognostic marker than any
measures of angiographic CAD burden.
There are practical implications of our findings. We believe that an
excess volume reflected by left atrial hypertension may have a role not
only in causing resting hypertension, but a hypertensive response as
well. Achieving euvolemic status may help achieve better blood pressure
control. We have observed this in our dedicated pre-renal transplant
cardiac clinic. As left atrial hypertension may exist without right
atrial hypertension, focused Doppler studies may be helpful to achieve
dry weights (31). Coronary angiography for detecting significant lesions
may not be a good tool in ESRD patients who have severely calcified,
diffusely diseased vessels. Coronary anatomic-physiological relationship
warrants further investigations in ESRD patients. Validity of DSE in
ESRD patients perhaps should be tested against direct measures of
myocardial perfusion and metabolism rather than coronary angiography
which may not be a perfect tool. One should also be vary of false
negative DSE in the presence of cavity obliteration which reduces wall
stress and may mask or attenuate ischemia.
Study Limitations: The main study limitations include its
observational nature. In view of severely calcified diffusely diseased
vessels, a better measure of significant lesion may be needed in
patients with ESRD. Blood pressure measurements were by sphygmomanometer
on an available limb. This may not be a very accurate reflection of
central aortic pressure because of stiff calcified arteries as well as
because of possibly undiagnosed peripheral vascular stenosis.
Conclusions: ESRD patient have high prevalence of hypertensive
response to dobutamine stress (21%) compared to general population and
this was predicted mainly by higher resting systolic and pulse
pressures. Stress induced wall motion abnormalities are common in
patients with a hypertensive response and half of these are false
positive compared to quantitative coronary angiography. Stress induced
wall motion abnormality in patients with a normotensive response
predicts higher mortality irrespective of angiographic findings.