Prognostic Value of Coronary Flow Reserve in Patients with Dialysis-Dependent ESRD

Abstract

Capillary rarefaction of the coronary microcirculation is a consistent phenotype in patients with dialysisdependent ESRD (dd-ESRD) and may help explain their excess mortality. Global coronary flow reserve (CFR) assessed by positron emission tomography (PET) is a noninvasive, quantitative marker of myocardial perfusion and ischemia that integrates the hemodynamic effects of epicardial stenosis, diffuse atherosclerosis, and microvascular dysfunction. We tested whether global CFR provides risk stratification in patients with dd-ESRD. Consecutive patients with dd-ESRD clinically referred for myocardial perfusion PET imaging were retrospectively included, excluding patients with prior renal transplantation. Perpatient CFR was calculated as the ratio of stress to rest absolute myocardial blood flow. Multivariable Cox proportional hazards models, including age, overt cardiovascular disease, and myocardial scar/ischemia burden, were used to assess the independent association of global CFR with all-cause and cardiovascular mortality. The incremental value of global CFR was assessed with relative integrated discrimination index and net reclassification improvement. In 168 patients included, median global CFR was 1.4 (interquartile range, 1.2-1.8). During follow-up (median of 3 years), 36 patients died, including 21 cardiovascular deaths. Log-transformed global CFR independently associated with all-cause mortality (hazard ratio, 0.01 per 0.5-unit increase; 95% confidence interval, ,0.01 to 0.14; P,0.001) and cardiovascular mortality (hazard ratio, 0.01 per 0.5-unit increase; 95% confidence interval, ,0.01 to 0.15; P=0.002). For all-cause mortality, addition of global CFR resulted in risk reclassification in 27% of patients. Thus, global CFR may provide independent and incremental risk stratification for all-cause and cardiovascular mortality in patients with dd-ESRD.

Clinical Quantification of Myocardial Blood Flow Using PET: Joint Position Paper of the SNMMI Cardiovascular Council and the ASNC

“…108 Two series from one center have shown that PET measures of MFR have greater prognostic value than do clinical and relative MPI parameters in patients with chronic kidney disease 109 and patients requiring renal replacement therapy. 110 Cardiomyopathy and Heart Failure. In many cases, relative MPI lacks sufficient negative predictive value to adequately rule out an ischemic etiology in patients with severe reductions in systolic function.…”

“…(Adapted from Naya et al 91 ). [159][160][161][162][163] and chronic kidney disease 109,110,164,165 ).…”

Diagnosis and Management of Cardiovascular Disease in Advanced and End‐Stage Renal Disease

“…Although the accuracy of dobutamine stress echocardiogram and SPECT in detecting obstructive CAD (≥70% stenosis) in renal transplantation candidates was not statistically different in a meta‐analysis,33 the presence of concentric and eccentric LVH, common in ESRD, may affect the accuracy of dobutamine stress echocardiogram 34. PET imaging assesses not only myocardial blood flow but also coronary flow reserve, which can provide additional insights into early stages of atherosclerosis and microvascular dysfunction 35, 36. Recently, coronary flow reserve assessed by cardiac PET has been shown to provide incremental risk stratification for cardiovascular and all‐cause mortality in patients on dialysis, even in the absence of overt cardiovascular disease 36.…”

“…PET imaging assesses not only myocardial blood flow but also coronary flow reserve, which can provide additional insights into early stages of atherosclerosis and microvascular dysfunction 35, 36. Recently, coronary flow reserve assessed by cardiac PET has been shown to provide incremental risk stratification for cardiovascular and all‐cause mortality in patients on dialysis, even in the absence of overt cardiovascular disease 36. For the highest risk patients, PET may be advantageous because it has superior sensitivity for detecting CAD 35, 36.…”

“…In such patients, noninvasive imaging with PET is a prudent second‐line investigation if coronary angiography is to be avoided because of advanced CKD and risk of progression to RRT. A normal PET stress test with abnormal multivessel coronary flow reserve is also a consideration for coronary angiography 36. Repeated evaluation is recommended on an annual basis in patients at high risk, with reevaluation every 3 years for low‐risk patients.…”