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.