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.