Methods:
Study subjects : We prospectively evaluated 575 consecutive ESRD
patients at our dedicated pre-transplant cardiology clinic for potential
renal transplant candidates between July 2008 and October 2010. Out of
these, 249 consecutive patients who underwent DSE as part of
preoperative cardiac risk stratification were included in the present
analysis (Figure 1). These patients were managed with very well with
regards to hypertension, diabetes and lipid control. The remaining 316
patients were risk stratified using pharmacological nuclear stress test
or dobutamine stress cardiac magnetic resonance imaging (CMR). DSE was
performed in between their dialysis days, usually a day after
hemodialysis. The study was approved by our Institutional Review Board.
Data were recorded as part of our ongoing prospective registry. All had
comprehensive history, physical examination and an echocardiogram.
Medication data including antihypertensive medications, anti-platelets,
diabetic medications and phosphate lowering therapies were entered after
medication reconciliation.
2-D echocardiograms: All echocardiograms were performed according
to American society of Echocardiography guidelines and interpreted by
level III trained echocardiographers (4-6). Left ventricular (LV)
ejection fraction was assessed by single or biplane Simpson’s method
(70%) when possible or by visual assessment when images were suboptimal
for quantification (30%). Myocardial contrast was not used for left
ventricular opacification. The inter and intra observer correlation was
excellent with an r value of 0.93. Elevated left atrial pressure was
defined as mitral annular E to E prime (E’) ratio> 15 and elevated right atrial pressure was
determined by <50% collapse of IVC during deep inspiration or
sniffing. Left atrial volume was calculated by biplane Simpson’s method
in end-systole.
Dobutamine Stress Test: The decision to perform dobutamine stress
test was taken after detailed clinical evaluation and analysis of
baseline echocardiograms. Patients on beta blockers (BB) and in some
cases on high doses of non-dihydropyridine calcium channel blockers
(CCB) were asked to hold their medications for 24 hours before the test.
Appropriate substitute medications for short term use were prescribed in
patients with uncontrolled BP for the time period when BB or CCB were on
hold. Standard dobutamine – atropine infusion protocol was used,
starting dobutamine at a dose of 10 microgram/kg body weight per minute
with incremental increase to 20, 30 or 40 microgram/kg/per min at
intervals of 3 minutes. In patients with resting wall motion
abnormalities dobutamine was started at 5 micrograms/kilograms/minute to
evaluate for contractile reserve. Atropine was used if dobutamine
infusion was not able to achieve 85% of maximum age predicted heart
rate in the absence of contraindications like glaucoma or symptoms of
prostatic obstruction. Vital signs were monitored throughout the test.
An electrocardiogram was obtained with each increase in dobutamine dose.
Resting and peak stress loop echocardiographic images in 4 views were
recorded. Test was terminated if patient had symptoms of chest pain or
new wall motion abnormality seen both on electrocardiogram and
echocardiogram, or development of significant arrhythmias like atrial
fibrillation, or non-sustained ventricular tachycardia. Test was also
terminated if patients had markedly elevated BP during stress (7). Not
achieving target heart rate was predominantly due to an indication to
terminate stress: new wall motion abnormalities (n=78), hypertensive
response (n=60), arrhythmias (n=13). In some, the target heart rate was
not achieved with dobutamine alone, but there was a contraindication for
the use of atropine (37%).Stress test data collected at rest, during
peak stress and up to 6 minutes into recovery were critically reviewed
by a two-level III trained attending echocardiographers. Information
about maximum dosage of dobutamine, atropine and double product of blood
pressure and heart rate was entered into the database. Stress test
results were considered positive for ischemia if a new wall motion
abnormality or worsening occurred compared to the baseline image.
Ischemia was defined as per American Society of Echocardiography (ASE)
guidelines (7).
Coronary Angiogram: The decision to refer for coronary angiogram
was done based upon outcomes of the stress test and overall cardiac risk
profile of individual patients. Coronary angiograms were quantitatively
analyzed (QCA) using GE software according to AHA’s classification and
description of coronary segments (8). Positive coronary angiogram was
defined as > 70% diameter stenosis in any of the
coronary segments. In patients with stenosis ranging between 50-70%
which were considered borderline fractional flow reserve (FFR) was used
to evaluate physiological significance.
Statistical Analysis: Statistical analysis was performed using
Stat View Inc. 2005 software. Student t- test or Chi-square tests were
used as appropriate to compare group characteristics. Logistic
regression analysis was used to further analyze the predictors of
hypertensive response. Survival analysis was performed using Kaplan
Meier analysis with log rank test. Mortality data was obtained from
clinic records and social security death index and patients were
censored on the date of transplant as transplant markedly improves
survival. A p value of < 0.05 was considered
significant. In multivariable predictive model for hypertensive
response, all predictors with p value of 0.10 or less were included.