Skip to main content
Top
Published in: Journal of Nuclear Cardiology 3/2016

01-06-2016 | Original Article

Prognostic value of heart rate response during regadenoson stress myocardial perfusion imaging in patients with end stage renal disease

Authors: Wael AlJaroudi, MD, MSc, FACC, FASNC, Tania Campagnoli, MD, Ibtihaj Fughhi, MD, MSc, Marwan Wassouf, MD, Amjad Ali, MD, Rami Doukky, MD, MSc, FACC, FASNC

Published in: Journal of Nuclear Cardiology | Issue 3/2016

Login to get access

Abstract

Background

Blunted heart rate response (HRR) to vasodilator stress agents is associated with worse outcomes. There are limited data assessing the effect of impaired HRR to regadenoson among patients with end-stage renal disease (ESRD) undergoing stress myocardial perfusion imaging (MPI).

Methods

We prospectively followed patients with ESRD enrolled in the ASSUAGE and ASSUAGE-CKD trials. HRR was defined as 100*(peak stress heart rate-resting heart rate)/resting heart rate. Study cohort was dichotomized to blunted and normal HRR groups according to an established median HRR value <28% or ≥28%, which were propensity-score matched based on 22 clinical and imaging covariates. The Primary endpoint was all-cause death. The secondary cardiac-specific endpoints included: (1) the composite endpoint of cardiac death or myocardial infarction; (2) the composite endpoint of cardiac death, myocardial infarction, or late (>90 days) coronary revascularization.

Results

There were 303 patients followed for 35 ± 10 months. In the entire cohort, there was a stepwise increase in the rates of death and all secondary endpoints with worsening HRR (P values ≤.001). Blunted HRR (<28%) was associated with increased risk of death (unadjusted hazard ratio 4.10 [1.98-8.46], P < .001) and all secondary endpoints (P ≤ .001). After multivariate adjustment, HRR remained an independent predictor of mortality and secondary endpoints whether used as continuous or dichotomous variable, and added incremental prognostic value for all-cause death (P = .046). Blunted HRR was associated with increased event rate among patients with normal myocardial perfusion (P = .001) and abnormal perfusion (P = .053). In the propensity-matched cohort of 132 patients (66 in each group), blunted HRR was associated with significant increase in all-cause death (21% vs. 5%, HR 5.09 [1.46-17.7], P=.011), and similarly for the secondary endpoints.

Conclusion

Blunted HRR (<28%) to regadenoson is a strong and independent predictor of death and cardiovascular events in patients with ESRD and adds incremental prognostic value.
Literature
1.
go back to reference Klocke FJ, Baird MG, Lorell BH, Bateman TM, Messer JV, Berman DS, et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging–executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging). Circulation 2003;108:1404-18.CrossRefPubMed Klocke FJ, Baird MG, Lorell BH, Bateman TM, Messer JV, Berman DS, et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging–executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging). Circulation 2003;108:1404-18.CrossRefPubMed
2.
go back to reference AMR/Arlington Medical Resources Inc. Myocardial Study Market Guide, Jan to Jun 2012; 2012. AMR/Arlington Medical Resources Inc. Myocardial Study Market Guide, Jan to Jun 2012; 2012.
4.
go back to reference Dhalla AK, Wong MY, Wang WQ, Biaggioni I, Belardinelli L. Tachycardia caused by A2A adenosine receptor agonists is mediated by direct sympathoexcitation in awake rats. J Pharmacol Exp Ther 2006;316:695-702.CrossRefPubMed Dhalla AK, Wong MY, Wang WQ, Biaggioni I, Belardinelli L. Tachycardia caused by A2A adenosine receptor agonists is mediated by direct sympathoexcitation in awake rats. J Pharmacol Exp Ther 2006;316:695-702.CrossRefPubMed
5.
go back to reference Hage FG, Heo J, Franks B, Belardinelli L, Blackburn B, Wang W, et al. Differences in heart rate response to adenosine and regadenoson in patients with and without diabetes mellitus. Am Heart J 2009;157:771-6.CrossRefPubMed Hage FG, Heo J, Franks B, Belardinelli L, Blackburn B, Wang W, et al. Differences in heart rate response to adenosine and regadenoson in patients with and without diabetes mellitus. Am Heart J 2009;157:771-6.CrossRefPubMed
6.
go back to reference Abidov A, Hachamovitch R, Hayes SW, Ng CK, Cohen I, Friedman JD, et al. Prognostic impact of hemodynamic response to adenosine in patients older than age 55 years undergoing vasodilator stress myocardial perfusion study. Circulation 2003;107:2894-9.CrossRefPubMed Abidov A, Hachamovitch R, Hayes SW, Ng CK, Cohen I, Friedman JD, et al. Prognostic impact of hemodynamic response to adenosine in patients older than age 55 years undergoing vasodilator stress myocardial perfusion study. Circulation 2003;107:2894-9.CrossRefPubMed
7.
go back to reference Hachamovitch R, Hayes SW, Friedman JD, Cohen I, Berman DS. A prognostic score for prediction of cardiac mortality risk after adenosine stress myocardial perfusion scintigraphy. J Am Coll Cardiol 2005;45:722-9.CrossRefPubMed Hachamovitch R, Hayes SW, Friedman JD, Cohen I, Berman DS. A prognostic score for prediction of cardiac mortality risk after adenosine stress myocardial perfusion scintigraphy. J Am Coll Cardiol 2005;45:722-9.CrossRefPubMed
8.
go back to reference Mathur S, Shah AR, Ahlberg AW, Katten DM, Heller GV. Blunted heart rate response as a predictor of cardiac death in patients undergoing vasodilator stress technetium-99m sestamibi gated SPECT myocardial perfusion imaging. J Nucl Cardiol 2010;17:617-24.CrossRefPubMed Mathur S, Shah AR, Ahlberg AW, Katten DM, Heller GV. Blunted heart rate response as a predictor of cardiac death in patients undergoing vasodilator stress technetium-99m sestamibi gated SPECT myocardial perfusion imaging. J Nucl Cardiol 2010;17:617-24.CrossRefPubMed
9.
go back to reference Venkataraman R, Hage FG, Dorfman TA, Heo J, Aqel RA, de Mattos AM, et al. Relation between heart rate response to adenosine and mortality in patients with end-stage renal disease. Am J Cardiol 2009;103:1159-64.CrossRefPubMed Venkataraman R, Hage FG, Dorfman TA, Heo J, Aqel RA, de Mattos AM, et al. Relation between heart rate response to adenosine and mortality in patients with end-stage renal disease. Am J Cardiol 2009;103:1159-64.CrossRefPubMed
10.
go back to reference Iqbal FM, Al Jaroudi W, Sanam K, Sweeney A, Heo J, Iskandrian AE, et al. Reclassification of cardiovascular risk in patients with normal myocardial perfusion imaging using heart rate response to vasodilator stress. Am J Cardiol 2013;111:190-5.CrossRefPubMed Iqbal FM, Al Jaroudi W, Sanam K, Sweeney A, Heo J, Iskandrian AE, et al. Reclassification of cardiovascular risk in patients with normal myocardial perfusion imaging using heart rate response to vasodilator stress. Am J Cardiol 2013;111:190-5.CrossRefPubMed
11.
go back to reference Hage FG, Dean P, Bhatia V, Iqbal F, Heo J, Iskandrian AE. The prognostic value of the heart rate response to adenosine in relation to diabetes mellitus and chronic kidney disease. Am Heart J 2011;162:356-62.CrossRefPubMed Hage FG, Dean P, Bhatia V, Iqbal F, Heo J, Iskandrian AE. The prognostic value of the heart rate response to adenosine in relation to diabetes mellitus and chronic kidney disease. Am Heart J 2011;162:356-62.CrossRefPubMed
12.
go back to reference Bhatheja R, Francis GS, Pothier CE, Lauer MS. Heart rate response during dipyridamole stress as a predictor of mortality in patients with normal myocardial perfusion and normal electrocardiograms. Am Heart J 2005;95:1159-64. Bhatheja R, Francis GS, Pothier CE, Lauer MS. Heart rate response during dipyridamole stress as a predictor of mortality in patients with normal myocardial perfusion and normal electrocardiograms. Am Heart J 2005;95:1159-64.
13.
go back to reference Doukky R, Rangel MO, Wassouf M, Dick R, Alqaid A. Morales Demori R. The safety and tolerability of regadenoson in patients with end-stage renal disease: The first prospective evaluation. J Nucl Cardiol 2013;20:205-13.CrossRefPubMed Doukky R, Rangel MO, Wassouf M, Dick R, Alqaid A. Morales Demori R. The safety and tolerability of regadenoson in patients with end-stage renal disease: The first prospective evaluation. J Nucl Cardiol 2013;20:205-13.CrossRefPubMed
14.
go back to reference Aljaroudi W, Hermann D, Hage F, Heo J, Iskandrian AE. Safety of regadenoson in patients with end-stage renal disease. Am J Cardiol 2010;105:133-5.CrossRefPubMed Aljaroudi W, Hermann D, Hage F, Heo J, Iskandrian AE. Safety of regadenoson in patients with end-stage renal disease. Am J Cardiol 2010;105:133-5.CrossRefPubMed
15.
go back to reference Hausberg M, Kosch M, Harmelink P, Barenbrock M, Hohage H, Kisters K, et al. Sympathetic nerve activity in end-stage renal disease. Circulation 2002;106:1974-9.CrossRefPubMed Hausberg M, Kosch M, Harmelink P, Barenbrock M, Hohage H, Kisters K, et al. Sympathetic nerve activity in end-stage renal disease. Circulation 2002;106:1974-9.CrossRefPubMed
16.
go back to reference Ranpuria R, Hall M, Chan CT, Unruh M. Heart rate variability (HRV) in kidney failure: Measurement and consequences of reduced HRV. Nephrol Dial Transpl 2008;23:444-9.CrossRef Ranpuria R, Hall M, Chan CT, Unruh M. Heart rate variability (HRV) in kidney failure: Measurement and consequences of reduced HRV. Nephrol Dial Transpl 2008;23:444-9.CrossRef
17.
go back to reference Doukky R, Morales DR, Jain S, Kiriakos R, Mwansa V, Calvin JE. Attenuation of the side effect profile of regadenoson: A randomized double-blinded placebo-controlled study with aminophylline in patients undergoing myocardial perfusion imaging “The ASSUAGE trial”. J Nucl Cardiol 2012;19:448-57.CrossRefPubMed Doukky R, Morales DR, Jain S, Kiriakos R, Mwansa V, Calvin JE. Attenuation of the side effect profile of regadenoson: A randomized double-blinded placebo-controlled study with aminophylline in patients undergoing myocardial perfusion imaging “The ASSUAGE trial”. J Nucl Cardiol 2012;19:448-57.CrossRefPubMed
18.
go back to reference Doukky R, Rangel MO, Dick R, Wassouf M, Alqaid A, Margeta B. Attenuation of the side effect profile of regadenoson: A randomized double-blind placebo-controlled study with aminophylline in patients undergoing myocardial perfusion imaging and have severe chronic kidney disease—the ASSUAGE-CKD trial. Int J Cardiovasc Imaging 2013;29:1029-37.CrossRefPubMed Doukky R, Rangel MO, Dick R, Wassouf M, Alqaid A, Margeta B. Attenuation of the side effect profile of regadenoson: A randomized double-blind placebo-controlled study with aminophylline in patients undergoing myocardial perfusion imaging and have severe chronic kidney disease—the ASSUAGE-CKD trial. Int J Cardiovasc Imaging 2013;29:1029-37.CrossRefPubMed
19.
go back to reference Henzlova MJ, Cerqueira MD, Hansen CL, Taillefer R, Yao SS. ASNC imaging guidelines for nuclear cardiology procedures: Stress protocols and tracers. J Nucl Cardiol 2009;2009:1-13. Henzlova MJ, Cerqueira MD, Hansen CL, Taillefer R, Yao SS. ASNC imaging guidelines for nuclear cardiology procedures: Stress protocols and tracers. J Nucl Cardiol 2009;2009:1-13.
20.
go back to reference Ballany W, Mansour K, Morales Demori R, Al-Amoodi M, Doukky R. The impact of regimented aminophylline use on extracardiac radioisotope activity in patients undergoing regadenoson stress SPECT myocardial perfusion imaging: A substudy of the ASSUAGE trial. J Nucl Cardiol 2014;21:496–502.CrossRefPubMed Ballany W, Mansour K, Morales Demori R, Al-Amoodi M, Doukky R. The impact of regimented aminophylline use on extracardiac radioisotope activity in patients undergoing regadenoson stress SPECT myocardial perfusion imaging: A substudy of the ASSUAGE trial. J Nucl Cardiol 2014;21:496–502.CrossRefPubMed
21.
go back to reference Golzar Y, Olusanya A, Pe N, Dua SG, Golzar J, Gidea C, et al. The significance of automatically measured transient ischemic dilation in identifying severe and extensive coronary artery disease in regadenoson, single-isotope technetium-99m myocardial perfusion SPECT. J Nucl Cardiol 2015;22:526-34.CrossRefPubMed Golzar Y, Olusanya A, Pe N, Dua SG, Golzar J, Gidea C, et al. The significance of automatically measured transient ischemic dilation in identifying severe and extensive coronary artery disease in regadenoson, single-isotope technetium-99m myocardial perfusion SPECT. J Nucl Cardiol 2015;22:526-34.CrossRefPubMed
22.
go back to reference Doukky R, Frogge N, Bayissa YA, Balakrishnan G, Skelton JM, Confer K, et al. The prognostic value of transient ischemic dilatation with otherwise normal SPECT myocardial perfusion imaging: A cautionary note in patients with diabetes and coronary artery disease. J Nucl Cardiol 2013;20:774-84.CrossRefPubMed Doukky R, Frogge N, Bayissa YA, Balakrishnan G, Skelton JM, Confer K, et al. The prognostic value of transient ischemic dilatation with otherwise normal SPECT myocardial perfusion imaging: A cautionary note in patients with diabetes and coronary artery disease. J Nucl Cardiol 2013;20:774-84.CrossRefPubMed
23.
go back to reference Hage FG, Dean P, Iqbal F, Heo J, Iskandrian AE. A blunted heart rate response to regadenoson is an independent prognostic indicator in patients undergoing myocardial perfusion imaging. J Nucl Cardiol 2011;18:1086-1094.CrossRefPubMed Hage FG, Dean P, Iqbal F, Heo J, Iskandrian AE. A blunted heart rate response to regadenoson is an independent prognostic indicator in patients undergoing myocardial perfusion imaging. J Nucl Cardiol 2011;18:1086-1094.CrossRefPubMed
24.
go back to reference Hage FG, Ghimire G, Lester D, McKay J, Bleich S, El-Hajj S, et al. The prognostic value of regadenoson myocardial perfusion imaging. J Nucl Cardiol 2015. doi:10.1007/s12350-014-0050-y. Hage FG, Ghimire G, Lester D, McKay J, Bleich S, El-Hajj S, et al. The prognostic value of regadenoson myocardial perfusion imaging. J Nucl Cardiol 2015. doi:10.​1007/​s12350-014-0050-y.
25.
go back to reference Heinze G, Juni P. An overview of the objectives of and the approaches to propensity score analyses. Eur Heart J 2011;32:1704-8.CrossRefPubMed Heinze G, Juni P. An overview of the objectives of and the approaches to propensity score analyses. Eur Heart J 2011;32:1704-8.CrossRefPubMed
26.
go back to reference Bellam N, Veledar E, Dorbala S, Di Carli MF, Shah S, Eapen D, et al. Prognostic significance of impaired chronotropic response to pharmacologic stress Rb-82 PET. J Nucl Cardiol 2014;21:233-44.CrossRefPubMed Bellam N, Veledar E, Dorbala S, Di Carli MF, Shah S, Eapen D, et al. Prognostic significance of impaired chronotropic response to pharmacologic stress Rb-82 PET. J Nucl Cardiol 2014;21:233-44.CrossRefPubMed
27.
go back to reference Hage FG, Wackers FJ, Bansal S, Chyun DA, Young LH, Inzucchi SE, et al. The heart rate response to adenosine: A simple predictor of adverse cardiac outcomes in asymptomatic patients with type 2 diabetes. Int J Cardiol 2013;167:2952-7.CrossRefPubMedPubMedCentral Hage FG, Wackers FJ, Bansal S, Chyun DA, Young LH, Inzucchi SE, et al. The heart rate response to adenosine: A simple predictor of adverse cardiac outcomes in asymptomatic patients with type 2 diabetes. Int J Cardiol 2013;167:2952-7.CrossRefPubMedPubMedCentral
28.
go back to reference Parikh K, Appis A, Doukky R. Cardiac imaging for the assessment of patients being evaluated for kidney or liver transplantation. J Nucl Cardiol 2015;22:282-96.CrossRefPubMed Parikh K, Appis A, Doukky R. Cardiac imaging for the assessment of patients being evaluated for kidney or liver transplantation. J Nucl Cardiol 2015;22:282-96.CrossRefPubMed
29.
go back to reference Aggarwal H, AlJaroudi WA, Mehta S, Mannon R, Heo J, Iskandrian AE, et al. The prognostic value of left ventricular mechanical dyssynchrony using gated myocardial perfusion imaging in patients with end-stage renal disease. J Nucl Cardiol 2014;21:739-46.CrossRefPubMed Aggarwal H, AlJaroudi WA, Mehta S, Mannon R, Heo J, Iskandrian AE, et al. The prognostic value of left ventricular mechanical dyssynchrony using gated myocardial perfusion imaging in patients with end-stage renal disease. J Nucl Cardiol 2014;21:739-46.CrossRefPubMed
30.
go back to reference AlJaroudi W, Aggarwal H, Venkataraman R, Heo J, Iskandrian AE, Hage FG. Impact of left ventricular dyssynchrony by phase analysis on cardiovascular outcomes in patients with end-stage renal disease. J Nucl Cardiol 2010;17:1058-64.CrossRefPubMed AlJaroudi W, Aggarwal H, Venkataraman R, Heo J, Iskandrian AE, Hage FG. Impact of left ventricular dyssynchrony by phase analysis on cardiovascular outcomes in patients with end-stage renal disease. J Nucl Cardiol 2010;17:1058-64.CrossRefPubMed
31.
go back to reference Aljaroudi W, Koneru J, Iqbal F, Aggarwal H, Heo J, Iskandrian AE. Left ventricular mechanical dyssynchrony by phase analysis of gated single photon emission computed tomography in end-stage renal disease. Am J Cardiol 2010;106:1042-7.CrossRefPubMed Aljaroudi W, Koneru J, Iqbal F, Aggarwal H, Heo J, Iskandrian AE. Left ventricular mechanical dyssynchrony by phase analysis of gated single photon emission computed tomography in end-stage renal disease. Am J Cardiol 2010;106:1042-7.CrossRefPubMed
Metadata
Title
Prognostic value of heart rate response during regadenoson stress myocardial perfusion imaging in patients with end stage renal disease
Authors
Wael AlJaroudi, MD, MSc, FACC, FASNC
Tania Campagnoli, MD
Ibtihaj Fughhi, MD, MSc
Marwan Wassouf, MD
Amjad Ali, MD
Rami Doukky, MD, MSc, FACC, FASNC
Publication date
01-06-2016
Publisher
Springer US
Published in
Journal of Nuclear Cardiology / Issue 3/2016
Print ISSN: 1071-3581
Electronic ISSN: 1532-6551
DOI
https://doi.org/10.1007/s12350-015-0234-0

Other articles of this Issue 3/2016

Journal of Nuclear Cardiology 3/2016 Go to the issue