Adenosine Myocardial Perfusion Imaging Research Articles

Molecular Mechanisms of Adenosine Stress T1 Mapping.

Adenosine stress T1 mapping is an emerging magnetic resonance imaging method to investigate coronary vascular function and myocardial ischemia without application of a contrast agent. Using gene-modified mice and 2 vasodilators, we elucidated and compared the mechanisms of adenosine myocardial perfusion imaging and adenosine T1 mapping. Wild-type (WT), A2AAR-/- (adenosine A2A receptor knockout), A2BAR-/- (adenosine A2B receptor knockout), A3AR-/- (adenosine A3 receptor knockout), and eNOS-/- (endothelial nitric oxide synthase knockout) mice underwent rest and stress perfusion magnetic resonance imaging (n=8) and T1 mapping (n=10) using either adenosine, regadenoson (a selective A2AAR agonist), or saline. Myocardial blood flow and T1 were computed from perfusion imaging and T1 mapping, respectively, at rest and stress to assess myocardial perfusion reserve and T1 reactivity (ΔT1). Changes in heart rate for each stress agent were also calculated. Two-way ANOVA was used to detect differences in each parameter between the different groups of mice. Myocardial perfusion reserve was significantly reduced only in A2AAR-/- compared to WT mice using adenosine (1.06±0.16 versus 2.03±0.52, P<0.05) and regadenoson (0.98±026 versus 2.13±0.75, P<0.05). In contrast, adenosine ΔT1 was reduced compared with WT mice (3.88±1.58) in both A2AAR-/- (1.63±1.32, P<0.05) and A2BAR-/- (1.55±1.35, P<0.05). Furthermore, adenosine ΔT1 was halved in eNOS-/- (1.76±1.46, P<0.05) versus WT mice. Regadenoson ΔT1 was approximately half of adenosine ΔT1 in WT mice (1.97±1.50, P<0.05), and additionally, it was significantly reduced in eNOS-/- mice (-0.22±1.46, P<0.05). Lastly, changes in heart rate was 2× greater using regadenoson versus adenosine in all groups except A2AAR-/-, where heart rate remained constant. The major findings are that (1) although adenosine myocardial perfusion reserve is mediated through the A2A receptor, adenosine ΔT1 is mediated through the A2A and A2B receptors, (2) adenosine myocardial perfusion reserve is endothelial independent while adenosine ΔT1 is partially endothelial dependent, and (3) ΔT1 mediated through the A2A receptor is endothelial dependent while ΔT1 mediated through the A2B receptor is endothelial independent.

Quantification of myocardial perfusion reserve using dynamic SPECT images of patients with chronic kidney disease

BackgroundChronic kidney disease (CKD) is an independent risk factor for cardiovascular disorders. The aim of this study was to examine whether the quantitatively measured myocardial blood flow (MBF) or myocardial perfusion reserve (MPR), calculated by dynamic single photon emission computed tomography (SPECT) analysis using a cardiac cadmium zinc telluride (CZT) gamma camera, was related to renal dysfunction in patients with normal myocardial perfusion imaging (MPI) findings. MethodsThe study population consisted of 46 patients with CKD and 46 individuals without CKD (controls). Their MPR index was quantitatively measured using adenosine MPI with a cardiac CZT gamma camera. All assessments were with a single tissue compartment kinetic model. The K1 value was calculated on stress and at-rest images. To obtain the MPR index we divided K1 stress-by K1 at-rest values. ResultsThe at-rest K1 value was significantly higher and the MPR index was significantly lower in patients with CKD than those without CKD [CKD vs. controls: at-rest K1 value, 0.21 (0.17–0.25) vs. 0.19 (0.16–0.22), p=0.040; MPR index, 1.86 (1.69–2.22) vs. 2.19 (1.93–2.41), p<0.001]. The stress K1 values were not significantly different. ConclusionThe MPR index is significantly lower in CKD patients; this is considered as being mainly due to an increase in the at-rest K1 value.

Effects of caffeine on the detection of ischemia in patients undergoing adenosine stress cardiovascular magnetic resonance imaging

BackgroundAdenosine stress cardiovascular magnetic resonance (CMR) can detect significant coronary artery stenoses with high diagnostic accuracy. Caffeine is a nonselective competitive inhibitor of adenosine2A-receptors, which might hamper the vasodilator effect of adenosine stress, potentially yielding false-negative results. Much controversy exists about the influence of caffeine on adenosine myocardial perfusion imaging. Our study sought to investigate the effects of caffeine on ischemia detection in patients with suspected or known coronary artery disease (CAD) undergoing adenosine stress CMR.MethodsThirty patients with evidence of myocardial ischemia on caffeine-naïve adenosine stress CMR were prospectively enrolled and underwent repeat adenosine stress CMR after intake of 200 mg caffeine. Both CMR exams were then compared for evaluation of ischemic burden.ResultsDespite intake of caffeine, no conversion of a positive to a negative stress study occurred on a per patient basis. Although we found significant lower ischemic burden in CMR exams with caffeine compared to caffeine-naïve CMR exams, absolute differences varied only slightly (1 segment based on a 16-segment model, 3 segments on a 60-segment model, and 1 ml in total ischemic myocardial volume, p < 0.001 each). Moreover, no relevant ischemia (≥2 segments in a 16-segment model) was missed by prior ingestion of caffeine.ConclusionsAlthough differences were small and no relevant myocardial ischemia had been missed, prior consumption of caffeine led to significant reduction of ischemic burden, and might lower the high diagnostic and prognostic value of adenosine stress CMR. Therefore, we suggest that patients should still refrain from caffeine prior adenosine stress CMR tests.

The prognostic value of regadenoson myocardial perfusion imaging

BackgroundRegadenoson (REGA), a selective adenosine A2A receptor agonist, is the most widely used stress agent for SPECT myocardial perfusion imaging (MPI) in the United States. The diagnostic accuracy of REGA MPI is comparable to Adenosine MPI, but its prognostic value is not well defined. MethodsWe categorized 1,400 patients (700 consecutive normal and 700 consecutive abnormal REGA-MPIs) into 4 groups based on the perfusion defect size using automated quantitative analysis: Group 1: normal perfusion; Group 2: <10% of left ventricle; Group 3: 10%-20%; Group 4: >20%. The primary outcome was a composite of cardiac death, myocardial infarction (MI), and late coronary revascularization (CR >90 days after MPI). ResultsOf the 1,400 patients (42% male, 37% diabetes, 21% heart failure, 26% end-stage renal disease), the primary outcome occurred in 23% (17% cardiac death, 4% MI, 6% late CR) during 46 ± 18 months of follow-up and 8% had early CR (within 90 days of MPI). Early CR occurred in 0.4%, 9%, 17%, and 17% and the primary outcome in 10%, 27%, 31%, and 43% in Groups 1-4, respectively (P < .001 for both). In an adjusted Cox proportional model, the hazard ratio for the primary outcome was 2.68 (1.77-4.06), 3.32 (2.28-4.83), and 4.05 (2.78-5.91) for Groups 2-4 compared to Group 1. ConclusionREGA MPI provides powerful prognostic information that has important implications in patient management and can guide clinical practice.

Comparison of the prognostic value of regadenoson and adenosine myocardial perfusion imaging

BackgroundRegadenoson is now widely used in single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). However, the prognostic value of abnormal stress perfusion findings with regadenoson vs adenosine are unclear. The aim of this study was to evaluate the prognostic value of regadenoson SPECT and to compare it to that of adenosine SPECT. Methods and Results3698 consecutive patients undergoing either adenosine or regadenoson SPECT were assessed at 1 year for the endpoints of cardiovascular death and a composite endpoint of cardiovascular death or MI. Weighted Cox proportional hazards regression modeling with the inverse probability weighted (IPW) estimators method adjusting to propensity for agent was used to account for differences in baseline characteristics. Patients undergoing adenosine SPECT MPI had a significantly higher prevalence of smoking history, diabetes, hypertension, and prior myocardial infarction (P < .05, all). At 1 year of follow-up, there were 154 cardiovascular deaths and 204 with the composite endpoint of cardiovascular death or MI. Using IPW adjustment to propensity for agent in a model with stress agent, summed stress score (SSS) remained a significant predictor of the composite endpoint of cardiovascular death or MI (HR 1.36 CI 1.28-1.46; P < .0001) as well as cardiovascular death (HR 1.38 CI 1.28-1.49; P < .0001). The interaction of SSS with agent was not significant. Similar findings were seen with summed difference score (SDS). ConclusionsSSS derived from either adenosine or regadenoson SPECT MPI is a significant predictor of events and provides incremental prognostic information beyond basic clinical variables. We have shown for the first time that use of regadenoson vs adenosine as stress agent does not modify the prognostic significance of SSS. Similar findings were seen with SDS.

Early gated SPECT adenosine myocardial perfusion imaging may influence the therapeutic management of patients with coronary artery disease

The aim of the study was to investigate whether myocardial perfusion imaging at 15 min after injection (T15) is more accurate in detecting coronary artery disease than that at 45 min (T45). Two-day stress/rest 99mTc-tetrofosmin gated SPECT was performed at T15 and T45 in 50 patients. Coronary angiography was considered when poststress and resting images were discordant. Tracer washout rates were calculated for the myocardium, liver, and subdiaphragmatic region. Perfusion sum difference scores were derived using QPS software. T15 and T45 were discordant in 18/50 (36%) patients. In 16/18 patients (89%) discordant deficits were more apparent at T15. A total of 13/16 patients underwent coronary angiography, of whom 12 had coronary artery disease. Poststress, but not resting, left ventricular ejection fraction was lower at T15 (P=0.02). Sum difference scores were higher at T15 [2.2 (1.9)] than at T45 [1.6 (1.7); P<0.05]. Tracer washout rates from the liver [46 (13.3)%] and subdiaphragmatic region [36 (21.3)%] were significant (P<0.0001), but there was no change in myocardial activity. T15 detected more abnormalities than did T45. The reduction in left ventricular ejection fraction after stress may result from adenosine-induced poststunning at T15. Accordingly, the T15 protocol may be useful in the assessment of hibernating myocardium. Contrasting myocardial and hepatic washout rates may be attributable to differential ABC transporter expression.

Functional assessment of sequential coronary artery fistula and coronary artery stenosis with fractional flow reserve and stress adenosine myocardial perfusion imaging

Coronary artery fistula is an abnormal connection between one coronary artery to another coronary artery or cardiac chambers. The coronary artery fistula may cause significant shunting of blood and cause “pseudo-stenosis” or “steal phenomenon”. This will also accentuate pre-existing mild-moderate de novo coronary lesions with resultant greater pressure gradient difference across the lesions. Thus, fractional flow reserve can be a useful tool to guide intervention decision on the coronary artery fistula. There are very few published reports regarding the use of FFR to assess coronary artery fistula. In fact, there is no outcome data regarding the deferment of coronary artery fistula intervention when the FFR is not physiologically significant. This case highlighted the use of FFR to evaluate the functional significance of coronary fistula in the setting of ischemia evaluation and it was proven to be safe to defer intervention with good 3year clinical outcome. Stress adenosine myocardial perfusion imaging correlated with the FFR result.

CRT-408 The Difference in Accuracy between Regadenoson and Adenosine Myocardial Perfusion Imaging in Obese Patients

The accuracy of gated single-photon emission computed tomography (G-SPECT) in diagnosing coronary artery disease (CAD) is decreased in obese patients. However, the impact of different tracer protocol and stress type has on the influences on the accuracy of myocardial perfusion imaging (MPI) result

The effect of beta blocker withdrawal on adenosine myocardial perfusion imaging

BackgroundThe effect of beta blockers on myocardial blood flow (MBF) under vasodilators has been studied in several SPECT and PET myocardial perfusion imaging (MPI) studies with divergent results. The present study evaluated the effect of a beta blocker withdrawal on quantitative adenosine MBF and on MPI results. MethodsTwenty patients with beta blockers and CAD history were studied with quantitative adenosine N-13 ammonia PET. The first study was performed under complete medication and the second after beta blocker withdrawal. The PET studies were independently read with respect to MPI result and clinical decision making. ResultsGlobal MBF showed an increase from 180.2 ± 59.9 to 193.6 ± 60.8 mL·minute−1/100 g (P = .02) after beta blocker withdrawal. The segmental perfusion values were closely correlated (R2 = 0.82) over the entire range of perfusion values. An essentially different interpretation after beta blocker discontinuation was found in two cases (10%). ConclusionA beta blocker withdrawal induces an increase in adenosine MBF. In the majority of cases, MPI interpretation and decision making are independent of beta blocker intake. If a temporary beta blocker withdrawal before MPI is not possible or was not realized by the patient, it is appropriate to perform adenosine stress testing without loss of the essential MPI result.

THE PROGNOSTIC VALUE OF ABNORMAL REGADENOSON MYOPARDIAL PERFUSION IMAGING

Regadenoson (REGA), a new selective adenosine A (2A) receptor agonist, is now the most commonly widely used stress agent for myocardial perfusion imaging (MPI). Although the diagnostic accuracy of REGA MPI is comparable to Adenosine MPI, the prognostic value of abnormal MPI is not well defined.

Serendipitous Discovery of Non–Sestamibi-Avid Squamous Cell Lung Cancer Invading the Heart During Myocardial Perfusion Imaging

Scintigraphic and radiographic correlation of a non-sestamibi-avid lung mass invading the left ventricle serendipitously discovered during adenosine myocardial perfusion imaging is presented. The only clue to the presence of the mass was deformation of the anterior wall on SPECT myocardial perfusion imaging. This case serves as a reminder that although the appearance of pathology on a nuclear medicine imaging study is typically what is seen (specifically, increased radiopharmaceutical uptake), it can just as importantly be what is not seen.

Regadenoson: A focused update

Since its approval by the Food and Drug Administration in 2008, regadenoson has become the most commonly used vasodilator in the United States. Previous reviews have summarized the pre-clinical and clinical data on the use of regadenoson for myocardial perfusion imaging (MPI). Since then, data have emerged on the safety of this agent in special groups of patients such as those with chronic kidney disease, airway disease (asthma and chronic obstructive pulmonary disease), and liver disease. There has also been recent interest in the use of regadenoson in hybrid protocols with exercise as a way to improve patient tolerance and image quality. Finally, although regadenoson was approved for clinical use based on the agreement rate of regadenoson MPI and adenosine MPI with regards to perfusion abnormalities, data are now available on the prognostic data derived from regadenoson MPI. We will briefly summarize these recent reports here in a focused update on the use of regadenoson for MPI.

Reclassification of Cardiovascular Risk in Patients With Normal Myocardial Perfusion Imaging Using Heart Rate Response to Vasodilator Stress

Previous studies have shown that patients with normal vasodilator myocardial perfusion imaging (MPI) findings remain at a greater risk of future cardiac events than patients with normal exercise MPI findings. The aim was to assess improvement in risk classification provided by the heart rate response (HRR) in patients with normal vasodilator MPI findings when added to traditional risk stratification. We retrospectively studied 2,000 patients with normal regadenoson or adenosine MPI findings. Risk stratification was performed using Adult Treatment Panel III framework. Patients were stratified by HRR (percentage of increase from baseline) into tertiles specific to each vasodilator. All-cause mortality and cardiac death/nonfatal myocardial infarction (MI) ≤2 years from the index MPI were recorded. During follow-up, 11.8% patients died and 2.7% patients experienced cardiac death/nonfatal MI in the adenosine and regadenoson groups, respectively. The patients who died had a greater Framingham risk score (12 ± 4 vs 11 ± 4, p= 0.009) and lower HRR (22± 16 vs 32 ± 21, p <0.0001). In an adjusted Cox model, the lowest tertile HRR was associated with an increased risk of mortality (hazard ratio 2.1) and cardiac death/nonfatal MI (hazard ratio 2.9; p <0.01). Patients in the highest HRR tertile, irrespective of the Adult Treatment Panel III category, were at low risk. When added to the Adult Treatment Panel III categories, the HRR resulted in net reclassification improvement in mortality of 18% and cardiac death/nonfatal MI of 22%. In conclusion, a blunted HRR to vasodilator stress was independently associated with an increased risk of cardiac events and overall mortality in patients with normal vasodilator MPI findings. The HRR correctly reclassified a substantial proportion of these patients in addition to the traditional risk classification models and identified patients with normal vasodilator MPI findings, who had a truly low risk of events.

Comparison of the Prognostic Value of Normal Regadenoson With Normal Adenosine Myocardial Perfusion Imaging With Propensity Score Matching

The aim of this study was to test the hypothesis that patients with normal regadenoson myocardial perfusion imaging (MPI) have a low rate of cardiac events, similar to patients with normal adenosine MPI. Regadenoson, a new selective adenosine A(2A) receptor agonist, is now a widely used stress agent for MPI. The low rate of cardiac events in patients with normal adenosine MPI is well-documented, but the prognostic implications of a normal regadenoson MPI have not been examined and compared with those with adenosine. Data on primary composite endpoint (cardiac death, myocardial infarction, and coronary revascularization) were collected for 2,000 patients (1,000 regadenoson, and 1,000 adenosine stress) with normal myocardial perfusion and left ventricular ejection fraction referred for vasodilator MPI. In addition, propensity scores were used to assemble a balanced cohort of 505 pairs of patients who were balanced on 36 baseline characteristics. The primary endpoint occurred in 21 (2.1%; 1.1%/year) patients in the regadenoson group and 33 (3.3%; 1.7%/year) patients in the adenosine group (hazard ratio [HR] for regadenoson vs. adenosine: 0.62; 95% confidence interval [CI]: 0.36 to 1.08; p = 0.090). In the propensity-matched pairs, the primary endpoint occurred in 7 (1.4%; 0.7%/year) patients in the regadenoson group and 13 (2.6%; 1.3%/year) patients in the adenosine group (matched HR: 0.58; 95% CI: 0.23 to 1.48; p = 0.257). Cardiac deaths were infrequent in the entire sample and in the propensity-matched groups; the cardiac death rate was 0.9%/year and 1.15%/year in the regadenoson and adenosine groups (HR: 0.77; 95% CI: 0.42 to 1.43; p = 0.404) in the pre-match sample and 0.5%/year and 0.7%/year in the matched groups, respectively (HR: 0.83; 95% CI: 0.25 to 2.73; p = 0.763). Major cardiac events are infrequent in patients with normal regadenoson MPI. These findings provide assurance that normal MPI using a simpler stress protocol with regadenoson provides prognostic data similar to normal adenosine MPI.

The heart rate response to adenosine: A simple predictor of adverse cardiac outcomes in asymptomatic patients with type 2 diabetes

BackgroundThe Detection of Ischemia in Asymptomatic Diabetics (DIAD) study demonstrated a low 5-year hard cardiac event rate. We hypothesized that a blunted heart rate response (HRR, maximum percent change) to adenosine, a simple marker of cardiac autonomic neuropathy, will identify a cohort at higher cardiac risk. MethodsIn DIAD, 518 participants were randomized to screening adenosine myocardial perfusion imaging (MPI) and had available data. HRR <20% was considered abnormal. The primary endpoint was a composite of nonfatal myocardial infarction and cardiac death. ResultsDuring 4.7±0.9years of follow-up 15 (3%) participants experienced the primary outcome. Participants with lower HRR experienced more events than those with higher HRR (8%, 3%, 1%, for HRR <20% (n=79), 20–39% (n=182) and ≥40% (n=257), respectively, p=0.01). In a Cox proportional regression model that included MPI abnormalities and HRR, both were independently associated with cardiac events (p for model <0.001). HRR <20% was associated with 9-fold increased risk (p=0.007) and moderate/large abnormal MPI was associated with 6-fold increased risk (p=0.004). Participants with both abnormal MPI and HRR (n=8) were at highest risk for cardiac events (38%) whereas those with HRR ≥40%, irrespective of MPI abnormalities (n=234), were at extremely low risk (≤1%, log-rank p<0.001). ConclusionsIn DIAD, abnormal HRR to adenosine infusion is an independent predictor of cardiac events. This easily obtained marker of cardiac autonomic neuropathy identifies asymptomatic patients with type 2 diabetes mellitus at increased risk, particularly when associated with abnormal MPI, who may warrant further testing and more aggressive cardiovascular risk factor management.

Comparative assessment of rest and post-stress left ventricular volumes and left ventricular ejection fraction on gated myocardial perfusion imaging (MPI) and echocardiography in patients with transient ischaemic dilation on adenosine MPI: Myocardial stunning or subendocardial hypoperfusion?

BackgroundTransient ischaemic dilation (TID) on myocardial perfusion imaging (MPI) is an important finding, conveying a high risk of subsequent cardiac events. However, the mechanism leading to TID on MPI is not well elucidated. This study aimed to determine if TID is due to true LV cavity dilation and ventricular stunning, or is due to relative subendocardial hypoperfusion. Methods31 patients undergoing single-day Tc-99m adenosine sestamibi MPI were recruited. All had routine ECG-gated single-day rest-stress adenosine MPI, with transthoracic echocardiograms (echo) acquired concurrently at rest, and both immediately, and 2 hours, post-stress. Echocardiography was performed using a Vivid-7 (GE). LV volumes and LVEF were quantified blinded to MPI results, using biplane Simpson method on echo, and quantitatively (including TID) with QGS®, on MPI. ResultsPatients were divided into quartiles for TID, with the top quartile considered TID positive [TID+ 9/31 (TID ratio 1.3 ± 0.09)], and TID negative [TID− 22/31 (TID ratio 1.01 ± 0.04)]. There was good correlation between resting echo and MPI physical measurements (LVEDV r2 = 0.79, LVESV r2 = 0.9, and LVEF r2 = 0.75). On MPI, a significant drop in LVEF was observed between rest and early stress in the TID+ group (56.6% vs 46.5%, P < .002), as well as an increase in both LVESV (62 vs 79 mls, P < .0001) and LVEDV (113 vs 131 mls, P < .0001). However, no statistically significant change in LVEF, LVESV or LVEDV was identified on concurrent echo imaging (LVEF 57% vs 56%, P < .66; LVESV 48 vs 54 mls, P < .26; LVEDV 87 vs 97 mls, P < .299). No significant change in LVEF or ventricular volumes was noted in the TID− group by either echo or MPI. ConclusionTransient dilation of the left ventricle on adenosine MPI is not related to chamber enlargement and myocardial stunning, but is more likely a function of subendocardial hypoperfusion and impaired coronary flow reserve.

Effect of caffeine on adenosine-induced reversible perfusion defects assessed by automated analysis

ObjectivesThis prospective study investigated the effects of caffeine ingestion on the extent of adenosine-induced perfusion abnormalities during myocardial perfusion imaging (MPI). MethodsThirty patients with inducible perfusion abnormalities on standard (caffeine-abstinent) adenosine MPI underwent repeat testing with supplementary coffee intake. Baseline and test MPIs were assessed for stress percent defect, rest percent defect, and percent defect reversibility. Plasma levels of caffeine and metabolites were assessed on both occasions and correlated with MPI findings. ResultsDespite significant increases in caffeine [mean difference 3,106 μg/L (95% CI 2,460 to 3,752 μg/L; P < .001)] and metabolite concentrations over a wide range, there was no statistically significant change in stress percent defect and percent defect reversibility between the baseline and test scans. The increase in caffeine concentration between the baseline and the test phases did not affect percent defect reversibility (average change −0.003 for every 100 μg/L increase; 95% CI −0.17 to 0.16; P = .97). ConclusionThere was no significant relationship between the extent of adenosine-induced coronary flow heterogeneity and the serum concentration of caffeine or its principal metabolites. Hence, the stringent requirements for prolonged abstinence from caffeine before adenosine MPI—based on limited studies—appear ill-founded.

Effect of body mass index on the efficacy, side effect profile, and plasma concentration of fixed-dose regadenoson for myocardial perfusion imaging

BackgroundThere are limited data on the effect of body mass index (BMI) on the actions of fixed-dose regadenoson. The purpose of this study was to determine the effect of BMI on the efficacy, side effects, and plasma concentration of regadenoson for Myocardial Perfusion Imaging (MPI). Methods and ResultsThe study included 2,015 subjects from the ADVANCE MPI trials. Initial adenosine MPI was followed by randomization to regadenoson (400-μg bolus injection) or adenosine (6-minute infusion) MPI. Subjects were classified according to BMI into six categories from underweight (<20 kg/m2) to extremely obese (≥40 kg/m2). PK modeling was used to predict the effect of BMI on plasma regadenoson concentration (PRC). Adenosine-regadenoson agreement rates for the presence and extent of reversibility were similar across BMI categories (P > .05). The incidence of side effects was also similar across BMIs (P ≥ .06). Subjects were less likely to feel very or extremely uncomfortable after regadenoson vs adenosine in all groups with BMI ≥ 25 kg/m2, but this trend was not statistically significant in subjects with BMI 20-24 kg/m2 (P > .05). PRC was inversely related to BMI with 19% higher PRC in the underweight and 36% lower PRC in the extremely obese compared with a normal weight subject. ConclusionsBMI does not alter the efficacy of regadenoson MPI despite lower PRC in high BMI subjects, or its side effect profile despite higher PRC in low BMI subjects. Regadenoson is better tolerated than adenosine but this benefit seems to lose statistical significance in subjects with BMI < 25 kg/m2.

The prognostic value of the heart rate response to adenosine in relation to diabetes mellitus and chronic kidney disease

Myocardial perfusion imaging (MPI) is a useful method for risk assessment in patients with diabetes mellitus (DM) and chronic kidney disease (CKD), but these patients have a residual risk that is not accounted for by MPI. The objective of this study is to determine whether the heart rate response (HRR) to adenosine has an incremental prognostic value to MPI in high-risk patients. The study group included 879 (age 61 ± 13 years, 48% women, 58% white, 40% DM, 49% CKD) consecutive patients who underwent adenosine MPI. Chronic kidney disease was defined as an estimated glomerular filtration rate <60 mL/min per 1.73 m(2) or dialysis replacement therapy. An HRR <10% (change from baseline) was considered blunted. The outcome of interest was overall mortality. During a follow-up period of 40 ± 14 months, 212 patients (24%) died. Patients with DM (23.4% ± 16.3% vs 29.4% ± 21.4%, P < .0001) and CKD (22.7% ± 17.6% vs 30.5% ± 20.4%, P < .0001) had lower HRR as compared with patients without DM and CKD, respectively. A blunted HRR was associated with increased mortality in the overall population and in those with DM and CKD and helped in risk stratification when added to traditional MPI findings. In a Cox regression model, a blunted HRR was the strongest predictor of mortality (hazard ratio 2.8, P < .0001) and provided additional prognostic data to MPI (hazard ratio 1.9, P < .0001) after controlling for age, gender, race, history of myocardial infarction, DM, CKD, β-blocker use, and presence of chest pain. A blunted HRR to adenosine is an independent predictor of poor outcome, adds incremental value to MPI, and helps in better risk stratification in high-risk patient groups.

Attenuation of Adenosine-Induced Myocardial Perfusion Heterogeneity by Atenolol and Other Cardioselective β-Adrenoceptor Blockers: A Crossover Myocardial Perfusion Imaging Study

Little is known about the effect of chronic beta-blockade on adenosine actions. We sought to investigate the effect of oral beta-blockers on the presence, extent, and severity of myocardial perfusion abnormality induced by adenosine in patients with coronary artery disease. In this crossover study, 45 male patients with coronary artery disease on beta-blocker therapy with atenolol, bisoprolol, or metoprolol underwent adenosine myocardial perfusion imaging both on and off beta-blockade in a random order on separate days. Myocardial perfusion was assessed both qualitatively and quantitatively. Hemodynamic response, image analysis, and sensitivity for the detection of coronary stenosis (>or=50% luminal diameter reduction on x-ray coronary angiography) were compared between the on and off beta-blocker studies. Rate pressure product both at baseline and at peak adenosine infusion decreased by 23% +/- 15% and 21% +/- 18%, respectively, after beta-blockade (P < 0.001 for all). The median (interquartile range) summed difference score, a measure of defect reversibility, and quantitative defect size were both significantly lower after beta-blockade (median, 7.0 [interquartile range, 2.0-9.5] vs. median, 5.0 [interquartile range, 0-8.0], P = 0.002; and quantitative defect size, 18% [interquartile range, 9%-34%] vs. quantitative defect size, 6% [interquartile range, 0%-19%], P < 0.001, respectively). The overall sensitivity for the detection of coronary stenosis decreased from 0.76 (95% confidence interval, 0.65-0.88) to 0.58 (95% confidence interval, 0.45-0.71) after beta-blockade (P = 0.03). beta-blockade causes a small but significant reduction in the extent and severity of perfusion abnormality by adenosine. This may reduce the diagnostic sensitivity of adenosine myocardial perfusion imaging for the detection of flow-limiting coronary stenosis.