Author + information
- Published online March 15, 2017.
- Mohammed A. Chamsi-Pasha, MD,
- Feng Xie, MD,
- Lynette M. Smith, PhD,
- Clifford Miles, MD and
- Thomas Porter, MD∗ ()
- ↵∗Department of Internal Medicine, Division of Cardiology, 982265 Nebraska Medical Center, 440 Emile Street, Omaha, Nebraska 68198
Cardiovascular disease accounts for 50% to 60% of all deaths in patients with end-stage renal disease (ESRD) (1). By adding myocardial perfusion (MP) imaging to wall motion (WM) analysis, real-time myocardial contrast echocardiography (RTMCE) increases the diagnostic sensitivity and prognostic value of the stress echocardiogram (2,3). However, its prognostic value in ESRD patients has not been defined. From the renal transplant database at the Nebraska Medical Center, patients with ESRD that underwent renal transplantation (RT) and stress RTMCE preoperatively between November 2008 and January 2014 were retrospectively identified (N = 487 patients). Patients’ demographics, comorbidities, and transplantation data were retrospectively retrieved from the electronic medical records.
Patients undergoing treadmill stress RTMCE underwent a symptom-limited Bruce protocol. Patients undergoing dobutamine stress echocardiography received intravenous dobutamine infusion with increasing doses at 3-min intervals up to 50 μ/kg/min combined with atropine. The contrast agent was Definity (Lantheus Medical, North Billerica, Massachusetts) administered as a 3% intravenous continuous infusion. Both MP and WM were analyzed simultaneously during the replenishment phase of contrast following high mechanical index impulses using a 17-segment model (3,4). Any abnormal MP or WM response had to be confirmed by a second independent expert reviewer, blinded to angiographic or clinical outcome data. Fixed or inducible segments were considered abnormal. All patients had baseline biplane Simpson’s measurements of ejection fraction, left atrial volume index, and diastolic function using current guidelines (4). Any subsequent angiograms were interpreted by an experienced interventional cardiologist, with 70% diameter stenosis in proximal or mid portions of the epicardial vessels or major branches considered significant. Patients were followed up for the primary outcome variable, event-free survival (EFS), defined as time from transplant to the incidence of myocardial infarction, heart failure hospitalization, or all-cause mortality. Kaplan-Meier method was used to estimate survival distributions and the log-rank tests were used to compare EFS distributions. Multivariate Cox regression models of EFS were conducted adjusting for clinically relevant variables (p value <0.10 on univariate analysis). A C-statistic was used to compute the predictive power of abnormal WM and MP in predicting EFS. Statistical analyses were carried out with SAS Software version 9.3 (SAS Institute, Cary, North Carolina).
Patients were followed for a median of 39 months (range 4 to 112 months). Forty-seven (10%) patients experienced an event (death in 24, myocardial infarction in 8, and heart failure hospitalization in 15). Three-year EFS following a negative RTMCE was 98% (95% confidence interval: 96% to 99%). Revascularizations (coronary bypass grafting or percutaneous intervention) were performed in 10 patients with abnormal studies prior to transplantation. There was no difference in the number of abnormal MP or WM segments for those that underwent revascularization versus those that did not undergo revascularization (p = 0.67 for MP, p = 0.26 for WM).
Patients with abnormal stress MP and grade II/III diastolic dysfunction were at a 5-fold higher risk of an event (hazard ratio: 5.1; 95% confidence interval: 1.8 to 14.6). EFS in patients with inducible MP or WM abnormalities that were not revascularized was significantly worse (p < 0.005; C-index 0.93 for both WM and MP). The extent of the MP defect (<2 segments, ≥2 segments) was also predictive of events (p = 0.02), while this same cutoff for abnormal WM was not as predictive (p = 0.06). In the multivariate backward-selected model, only older age (p = 0.023) and diabetes mellitus (p = 0.0033) were associated with higher risk of a major adverse cardiovascular event, along with a longer time interval between stress RTMCE and RT (HR: 1.02 for each month increase; p = 0.046) (Table 1).
This study demonstrates that MP analysis with RTMCE during demand stress echocardiography is helpful in identifying higher-risk ESRD patients. Patients who are not revascularized after an abnormal study are at significant risk for complications, especially if concomitant grade II/III diastolic dysfunction exists. Because revascularization decision making was based on angiographic obstruction within the abnormal RTMCE territory, this would indicate that abnormal RTMCE in the absence of a significant angiographic abnormality identifies high-risk patients with microvascular disease. Although this study was a single-center study and RTMCE requires expertise, the current study emphasizes the importance of microvascular and WM abnormalities during demand stress in predicting cardiovascular outcomes following RT.
Please note: Dr. Porter has received grant support from Lantheus Medical Imaging, Astellas Pharma, Phillips Research North America, and General Electric Global Research; and educational support from Bracco Research. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2017 American College of Cardiology Foundation
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