Evaluating Myocardial Ischemia and Sympathetic Innervation in Patients with Chronic Kidney Disease before and during Renal Replacement Therapy
using 99mTc-tetrofosmin and 123I-MIBG imaging

Cardiovascular diseases and autonomic dysfunction are the leading cause of
death in patients with chronic kidney disease (CKD). Cardiac causes account for
40% to 50% of all deaths in dialysis patients. About 15% to 20% of these deaths
occur suddenly and unexpectedly. Prevalence of coronary artery disease (CAD) in
CKD patients varies from 24% in young nondiabetic hemodialysis patients to 85%
in elderly diabetic uremic patients. However, there are a large, but as yet
unknown number of totally asymptomatic individuals, especially those with
diabetes who have myocardial ischemia. In diabetics, the lack of symptoms is
attributed to the concomitant presence of diabetic autonomic neuropathy.
Autonomic dysfunction is also commonly present in end-stage renal disease, but
whether this results in lack of symptoms in cardiac ischemia is unknown.
Studies in patients on maintenance hemodialysis (HD) have shown that HD is an
arrythmogenic process which can also induce myocardial ischemia6. HD patients
with a reduced heart rate variability (HRV) on a 24-hour ambulatory Holter ECG
monitoring seem to be at increased risk of all-cause mortality and sudden death
as recently shown in a relatively small prospective study. Imaging showed
reduced sympathetic activity in the heart of hemodialysis patients, especially
in diabetics. Another study has demonstrated electrocardiographic changes
during HD, significant ST depression during HD was highly associated with CAD
and it was an important prognosticator of subsequent cardiac events. Unknown is
the extent of cardial ischemia and sympathetic dysfunction induced in patients
receiving HD. It is known that in the normal population, cardiac ischemia and
autonomic dysfunction is a good predictor for future cardiac events and it is
also associated with increased long term mortality. Unclear is in which phase
renal failure CAD and autonomic dysfunction will develop in HD patients. This
may be during dialysis or even before starting dialysis.
Coronary angiography is the most effective method for detecting CAD, but its
cost is high and the risk of complications is significant.

Thus, coronary angiography is unsuitable as a screening tool for CAD in
asymptomatic patients. Further, coronary angiography can not evaluate ischemia
of (non-) significant stenosis. Hence, non-invasive imaging techniques for the
purpose of detecting myocardial ischemia has been used extensively in routine
clinical practice and increasingly in hemodialysis patients. ECG-gated
single-photon emission computed tomography (SPECT) myocardial perfusion
scintigraphy using technetium-99m tetrofosmin (99mTc-tetrofosmin) is one of
these modalities. Gated 99mTc-tetrofosmin SPECT assesses in one session
myocardial ischemia, wall motion, left ventricular volumes and ejection
fraction. Analysis of the autonomic function of the heart can also be performed
by 123I-MIBG imaging, a well established additional method to evaluate the
sympathetic innervation of the heart 15.
Thus far the presence and severity of CAD and autonomic dysfunction of the
heart has never been studied in asymptomatic patients with stage 5 CKD who are
not yet on dialysis (HD) using 99mTc-tetrofosmin and 123I-MIBG imaging. For
that reason we want to evaluate myocardial ischemia and sympathetic innervation
before starting HD with 99mTc-tetrofosmin and 123I-MIBG. The result of the
pre-dialysis patients will be compared in the same patients 3 months after
starting HD to evaluate the effect of hemodialysis on myocardial perfusion and
innervation

Is sympathetic innervation and perfusion disturbed in patients with chronic
kidney disease and will is change after HD?

This study will include patients before starting dialysis (pre-dialysis). The
design of the study will be longitudinal. Cardial ischemia and innervation will
be assessed in the pre-dialysis period and 3 months after starting HD in the
same patients. Cardiac ischemia will be visualized by using 99mTc-tetrofosmin
rest and adenosine stress SPECT method and analyzed on a 4D-MSPECT-software
program. 123I-MIBG imaging will be performed 15 min and 3.5 hours after
injection. Heart-to-the-mediatinum ratio and wash-out rate of 123I-MIBG will be
calculated. Perfusion and innervation assessment of the heart is of evidenced
clinical value. All scans in the pre-dialysis phase will therefore be performed
in a clinical setting.
Also a normal database of the heart will be collected by 10 regular clinical
patients with medullar thyroid carcinoma or paraganglioma that will receive a
clinical 123I-MIBG scan. Only an extra image of 10 minutes will be performed in
these patients. No extra 123I-MIBG will be injected and this image can be
performed on the same day of injection of 123I-MIBG. A normal database is of
importance for an accurate assessment of 123I-MIBG uptake in the heart.

Little pain during/after injection. Small radiation dose. Lay down quietly for
30 minutes in the gammacamera.