Downward myocardial creep during stress PET imaging is inversely associated with mortality.

PURPOSE: The myocardial creep is a phenomenon in which the heart moves from its original position during stress-dynamic PET myocardial perfusion imaging (MPI) that can confound myocardial blood flow measurements. Therefore, myocardial motion correction is important to obtain reliable myocardial flow quantification. However, the clinical importance of the magnitude of myocardial creep has not been explored. We aimed to explore the prognostic value of myocardial creep quantified by an automated motion correction algorithm beyond traditional PET-MPI imaging variables. METHODS: Consecutive patients undergoing regadenoson rest-stress [82Rb]Cl PET-MPI were included. A newly developed 3D motion correction algorithm quantified myocardial creep, the maximum motion at stress during the first pass (60 s), in each direction. All-cause mortality (ACM) served as the primary endpoint. RESULTS: A total of 4,276 patients (median age 71 years; 60% male) were analyzed, and 1,007 ACM events were documented during a 5-year median follow-up. Processing time for automatic motion correction was < 12 s per patient. Myocardial creep in the superior to inferior (downward) direction was greater than the other directions (median, 4.2 mm vs. 1.3-1.7 mm). Annual mortality rates adjusted for age and sex were reduced with a larger downward creep, with a 4.2-fold ratio between the first (0 mm motion) and 10th decile (11 mm motion) (mortality, 7.9% vs. 1.9%/year). Downward creep was associated with lower ACM after full adjustment for clinical and imaging parameters (adjusted hazard ratio, 0.93; 95%CI, 0.91-0.95; p < 0.001). Adding downward creep to the standard PET-MPI imaging model significantly improved ACM prediction (area under the receiver operating characteristics curve, 0.790 vs. 0.775; p < 0.001), but other directions did not (p > 0.5). CONCLUSIONS: Downward myocardial creep during regadenoson stress carries additional information for the prediction of ACM beyond conventional flow and perfusion PET-MPI. This novel imaging biomarker is quantified automatically and rapidly from stress dynamic PET-MPI.

Reduced response to regadenoson with increased weight: an artificial intelligence based quantitative myocardial perfusion study.

BACKGROUND: There is conflicting evidence regarding the response to a fixed dose of regadenoson in patients with high body weight. The aim of this study was to evaluate the effectiveness of regadenoson in patients with varying body weights using novel quantitative CMR perfusion parameters in addition to standard clinical markers. METHODS: Consecutive patients with typical angina and/or risk factors for coronary artery disease (N=217) underwent regadenoson stress CMR perfusion imaging using a dual-sequence quantitative protocol with perfusion parameters generated from an artificial intelligence (AI) based algorithm. CMR was performed on 1.5T scanners using a standard 0.4mg injection of regadenoson. A cohort of consecutive patients undergoing adenosine stress perfusion (N=218) was used as a control group. RESULTS: An inverse association of myocardial perfusion reserve and weight (mean decrease -0.05 per 10Kg increase, 95% CI -0.009/-0.0001, P=0.045) was noted in the regadenoson group but not in patients stressed with adenosine (P=0.77). Adjusted logistic regression analysis revealed a 10Kg increase resulted in 36% increased odds for inadequate stress response (OR= 1.36, 95% CI 1.10-1.69, P=0.005). Moreover, a significant interaction (OR=1.09, 95% CI 1.02-1.16, P=0.012) between stressor type (regadenoson vs adenosine) and weight was noted. This was also confirmed in the propensity matched subgroup (P=0.024) and was not attenuated after adjustment (P=0.041). BSA (P=0.006) but not BMI (P=0.055) was differentially associated with inadequate response conditional to the stressor used, and this association remained significant after adjustment for confounders (P=0.025). Patients in the highest quartile of weight (>93Kg) or BSA (>2.06m2) had substantially increased odds for inadequate response with regadenoson (OR=8.19, 95% CI 2.04-32.97, P=0.003 for increased weight and OR=7.75, 95% CI 1.93- 31.13, P=0.004 for increased BSA). Both weight and BSA had excellent discriminative ability for inadequate regadenoson response (ROC area under curve 0.84 and 0.83 respectively). CONCLUSIONS: Using quantitative perfusion CMR in patients undergoing pharmacological stress with regadenoson, we found an inverse relationship between patient weight and both clinical response and myocardial perfusion parameters. A fixed-dose bolus approach may not be adequate to induce maximal hyperemia in patients with increased weight. Weight-adjusted stressors like adenosine may be considered instead in patients with body weight > 93Kg and BSA > 2.06m2.

Splenic switch-off in regadenoson 82Rb-PET myocardial perfusion imaging: assessment of clinical utility.

BACKGROUND: Splenic switch-off (SSO) is a phenomenon describing a decrease in splenic radiotracer uptake after vasodilatory stress. We aimed to assess the diagnostic utility of regadenoson-induced SSO. METHODS: We included consecutive patients who had clinically indicated Regadenoson Rb-82 PET-MPI for suspected CAD. This derivation cohort (no perfusion defects and myocardial flow reserves (MFR) ≥ 2) was used to calculate the splenic response ratio (SRR). The validation cohort was defined as patients who underwent both PET-MPI studies and invasive coronary angiography (ICA). RESULTS: The derivation cohort (n = 100, 57.4 ± 11.6 years, 77% female) showed a decrease in splenic uptake from rest to stress (79.9 ± 16.8 kBq⋅mL vs 69.1 ± 16.2 kBq⋅mL, P < .001). From the validation cohort (n = 315, 66.3 ± 10.4 years, 67% male), 28% (via SRR = 0.88) and 15% (visually) were classified as splenic non-responders. MFR was lower in non-responders (SRR; 1.55 ± 0.65 vs 1.76 ± 0.78, P = .02 and visually; 1.18 ± 0.33 vs 1.79 ± 0.77, P < .001). Based on ICA, non-responders were more likely to note obstructive epicardial disease with normal PET scans especially in patients with MFR < 1.5 (SRR; 61% vs 34% P = .05 and visually; 68% vs 33%, P = .01). CONCLUSION: Lack of splenic response based on visual or quantitative assessment of SSO may be used to identify an inadequate vasodilatory response.

Rest/stress myocardial perfusion imaging by positron emission tomography with 18F-Flurpiridaz: A feasibility study in mice.

BACKGROUND: Myocardial perfusion imaging by positron emission tomography (PET-MPI) is the current gold standard for quantification of myocardial blood flow. 18F-flurpiridaz was recently introduced as a valid alternative to currently used PET-MPI probes. Nonetheless, optimum scan duration and time interval for image analysis are currently unknown. Further, it is unclear whether rest/stress PET-MPI with 18F-flurpiridaz is feasible in mice. METHODS: Rest/stress PET-MPI was performed with 18F-flurpiridaz (0.6-3.0 MBq) in 27 mice aged 7-8 months. Regadenoson (0.1 µg/g) was used for induction of vasodilator stress. Kinetic modeling was performed using a metabolite-corrected arterial input function. Image-derived myocardial 18F-flurpiridaz uptake was assessed for different time intervals by placing a volume of interest in the left ventricular myocardium. RESULTS: Tracer kinetics were best described by a two-tissue compartment model. K1 ranged from 6.7 to 20.0 mL·cm-3·min-1, while myocardial volumes of distribution (VT) were between 34.6 and 83.6 mL·cm-3. Of note, myocardial 18F-flurpiridaz uptake (%ID/g) was significantly correlated with K1 at rest and following pharmacological vasodilation for all time intervals assessed. However, while Spearman's coefficients (rs) ranged between 0.478 and 0.681, R2 values were generally low. In contrast, an excellent correlation of myocardial 18F-flurpiridaz uptake with VT was obtained, particularly when employing the averaged myocardial uptake from 20 to 40 min post tracer injection (R2 ≥ 0.98). Notably, K1 and VT were similarly sensitive to pharmacological vasodilation induction. Further, mean stress-to-rest ratios of K1, VT, and %ID/g 18F-flurpiridaz were virtually identical, suggesting that %ID/g 18F-flurpiridaz can be used to estimate coronary flow reserve (CFR) in mice. CONCLUSION: Our findings suggest that a simplified assessment of relative myocardial perfusion and CFR, based on image-derived tracer uptake, is feasible with 18F-flurpiridaz in mice, enabling high-throughput mechanistic CFR studies in rodents.

The prognostic utility of regadenoson SPECT myocardial perfusion imaging in patients with end-stage renal disease: The largest cohort to date.

BACKGROUND: There are limited data on the prognostic utility of regadenoson SPECT myocardial perfusion imaging (MPI) in patients with end-stage renal disease (ESRD). METHODS AND RESULTS: In a single-center, retrospective study, we analyzed consecutive ESRD patients who underwent regadenoson SPECT-MPI. The severity of MPI abnormalities and ischemic burden were determined quantitatively. The primary endpoint was major adverse cardiac events (MACE), defined as the composite of cardiac death or myocardial infarction. Among 1,227 subjects (mean age 54 ± 13 years, 47% men), 60 (5%) MACE were observed during a mean follow-up of 2.5 ± 1.8 years. The presence and severity of MPI abnormalities and ischemic burden were associated with a stepwise increase in MACE risk. Abnormal MPI (SSS ≥ 4) was associated with increased MACE risk, independent and incremental to relevant clinical covariates; adjusted hazard ratio, 1.95; 95% confidence interval, 1.15-3.32; Δχ2 = 5.97; P = .013. Myocardial ischemia (SDS ≥ 2) was associated with a trend towards increased MACE risk; adjusted hazard ratio, 1.63; 95% confidence interval, 0.96-2.77; Δχ2 = 3.12; P = .072. CONCLUSION: In the largest cohort to date, we demonstrated the incremental prognostic value of abnormal MPI in predicting MACE risk in ESRD patients. Given its size, our study provides improved risk estimates in this population compared to previous reports.

Effect of temporal sampling protocols on myocardial blood flow measurements using Rubidium-82 PET.

BACKGROUND: A variety of temporal sampling protocols is used worldwide to measure myocardial blood flow (MBF). Both the length and number of time frames in these protocols may alter MBF and myocardial flow reserve (MFR) measurements. We aimed to assess the effect of different clinically used temporal sampling protocols on MBF and MFR quantification in Rubidium-82 (Rb-82) PET imaging. METHODS: We retrospectively included 20 patients referred for myocardial perfusion imaging using Rb-82 PET. A literature search was performed to identify appropriate sampling protocols. PET data were reconstructed using 14 selected temporal sampling protocols with time frames of 5-10 seconds in the first-pass phase and 30-120 seconds in the tissue phase. Rest and stress MBF and MFR were calculated for all protocols and compared to the reference protocol with 26 time frames. RESULTS: MBF measurements differed (P ≤ 0.003) in six (43%) protocols in comparison to the reference protocol, with mean absolute relative differences up to 16% (range 5%-31%). Statistically significant differences were most frequently found for protocols with tissue phase time frames < 90 seconds. MFR did not differ (P ≥ 0.11) for any of the protocols. CONCLUSIONS: Various temporal sampling protocols result in different MBF values using Rb-82 PET. MFR measurements were more robust to different temporal sampling protocols.

Regadenoson versus dipyridamole: Evaluation of stress myocardial blood flow response on a CZT-SPECT camera.

BACKGROUND: Regadenoson is a selective adenosine receptor agonist. It is currently unclear if the level of hyperemia differs between stress agents. We compared Myocardial Blood Flow (MBF) and Myocardial Flow Reserve (MFR) response on CZT-SPECT Myocardial Perfusion Imaging (MPI) to evaluate if dipyridamole and regadenoson could induce the same level of hyperemia. METHODS: 228 patients with dynamic CZT-SPECT MPI were retrospectively analyzed (66 patients stressed with regadenoson and 162 with dipyridamole) in terms of MBF and MFR. To rule out confounding factors, two groups of 41 patients were matched for clinical characteristics in a sub-analysis, excluding high cardiovascular risk patients. RESULTS: Overall stress MBF was higher in regadenoson patients (1.71 ± 0.73 vs. 1.44 ± 0.55 mL·min-1·g-1 for regadenoson and dipyridamole, respectively, p < .05). However, when confounding factors were ruled out, stress MBF (1.57 ± 0.56 vs. 1.61 ± 0.62 mL·min-1·g-1 for dipyridamole and regadenoson, respectively, p = .88) and MFR (2.62 ± 0.77 vs. 2.46 ± 0.76 for dipyridamole and regadenoson, respectively, p = .40) were not different between regadenoson and dipyridamole. CONCLUSIONS: Our results suggest that dipyridamole and regadenoson induce equivalent hyperemia in dynamic SPECT with similar stress MBF and MFR in comparable patients.

The prognostic implications of ST-segment and T-wave abnormalities in patients undergoing regadenoson stress SPECT myocardial perfusion imaging.

BACKGROUND: The prognostic implications of ST-segment and T-wave (ST/T) abnormalities in patients undergoing stress SPECT-myocardial perfusion imaging (MPI) are not well defined. METHODS AND RESULTS: This was a single-center, retrospective cohort study of consecutive patients who underwent regadenoson stress SPECT-MPI. Patients with baseline electrocardiogram (ECG) abnormalities that impede ST/T analysis or those with known coronary artery disease were excluded. Patients were categorized as having primary ST abnormalities, secondary ST/T abnormalities due to ventricular hypertrophy or right bundle branch block, T-wave abnormalities, or normal ECG. The primary outcome was major adverse cardiovascular events (MACE) defined as the composite of cardiac death or myocardial infarction. Among 6,059 subjects, 1912 (32%) had baseline ST/T abnormalities. During a mean follow-up of 2.3 ± 1.9 years, the incidence of MACE was significantly higher among patients with secondary ST/T abnormalities compared to those with normal ECG (HR 2.05; 95% confidence interval [CI], 1.04-4.05; P = 0.039). No significant difference in MACE was observed among patients with primary ST abnormalities (HR 1.64; CI 0.87-3.06; P = 0.124) or T-wave abnormalities (HR 1.15; CI 0.62-2.16; P = 0.658) compared with patients who had normal ECG. Among patients with secondary ST/T changes, abnormal MPI was not associated with a significant increase in MACE rates compared to normal MPI (HR 1.18; CI 0.31-4.58; P = 0.808). However, abnormal MPI was associated with higher MACE rates among patients with primary ST abnormalities (HR 4.50; CI 1.44-14.10; P = 0.005) and T-wave abnormalities (HR 3.74; CI 1.20-11.68; P = 0.015). Similarly, myocardial ischemia on regadenoson stress SPECT-MPI was not associated with a significant increase in MACE rates in patients with secondary ST/T abnormalities (HR 1.45; CI 0.38-5.61; P = 0.588), while it was associated with a higher incidence of MACE in patients with primary ST abnormalities (HR 3.012; CI 0.95-9.53; P = 0.049) and T-wave abnormalities (HR 5.06; CI 1.60-15.96; P = 0.002). CONCLUSION: While patients with secondary ST/T abnormalities had significantly higher MACE risk, abnormal MPI or presence of myocardial ischemia on regadenoson SPECT-MPI in this group does not add prognostic information. Patients with primary ST abnormalities and T-wave abnormalities do not seem to have a significantly higher MACE risk compared to those with normal ECG; however, abnormal MPI or presence of myocardial ischemia, in these groups, correlates with higher MACE rates.

Comparison of left ventricle mechanical dyssynchrony parameters in ischemic and non-ischemic patients using 13N-NH3 PET/CT.

BACKGROUND-AIM: The relationship between perfusion pattern and stress-induced changes in Left Ventricular Mechanical Dyssynchrony (LVMD) has been previously described with controversial results using stress-rest perfusion imaging studies. The aim of this study was to assess the relationship between perfusion pattern and stress-induced changes in LVMD usingo regadenoson/rest13N-NH3 PET/CT. METHODS: There were 74 patients who underwent stress-rest 13N-NH PET/CT from January 2014 to October 2018 excluding patients with left bundle branch block, ventricular pacing and myocardial necrosis. The patients were divided into those with reversible perfusion defects at stress (Ischemic group, n = 18) and patients without reversible perfusion defects (non-ischemic group, n = 56). The LVMD parameters included: phase standard deviation (PSD) and phase histogram bandwidth (PHB), after stress and at rest. The ΔPSD (post-stressPSD-restPSD) and ΔPHB (post-stressPHB-restPHB) were calculated to measure stress-induced changes in LVMD. RESULTS: There were no significant differences in LVMD parameters between post-stress and at rest in both groups. The PSD post-stress, ΔPSD and PHB post-stress were significantly higher in the ischemic group. CONCLUSIONS: Using a vasodilator as a stress, the PSD and PHB post-stress and ΔPSD were significantly higher in the ischemic patients than the non-ischemic group, while there were no significant differences in each cohort between stress and rest indices.

The diagnostic and prognostic value of near-normal perfusion or borderline ischemia on stress myocardial perfusion imaging.

BACKGROUND: Data on the diagnostic and prognostic value of subtle abnormalities on myocardial perfusion imaging (MPI) are limited. METHODS AND RESULTS: In a retrospective single-center cohort of patients who underwent regadenoson SPECT-MPI, near-normal MPI was defined as normal left ventricular ejection fraction (LVEF ≥ 50%) and a summed stress score (SSS) of 1-3 vs SSS = 0 in normal MPI. Borderline ischemia was defined as normal LVEF, SSS = 1-3, and a summed difference score (SDS) of 1 vs SDS = 0 in the absence of ischemia. Coronary angiography data within 6 months from MPI were tabulated. Patients were followed for cardiac death (CD), myocardial infarction (MI), coronary revascularization (CR), and Late CR (LCR) [> 90 days post MPI]. Among 6,802 patients (mean age, 62 ± 13 years; 42% men), followed for a mean of 2.5 ± 2.1 years, 4,398 had normal MPI, 2,404 had near-normal MPI, and 972 had borderline ischemia. Among patients who underwent angiography within 6 months, obstructive (≥ 70% or left main ≥ 50%) CAD was observed at higher rates among subjects with near-normal MPI (33.5% vs 25.5%; P = .049) and those with borderline ischemia (40.5% vs 25.8%; P = .004). During follow-up, 158 (2.3%) CD/MI, 246 (3.6%) CR, and 150 (2.2%) LCR were observed. Near-normal MPI (SSS = 1-3), compared to normal MPI (SSS = 0), was not associated with a significant difference in the risk of the composite endpoint of CD/MI (Hazard ratio [HR], 1.21; 95% confidence interval [CI], .88-1.66; P = .243) or LCR (HR 1.28; CI .93-1.78; P = .130), but was associated with a significant increase in the risk of CR (HR 1.91; CI 1.49-2.46; P < .001). Borderline ischemia (SDS = 1), compared to no ischemia (SDS = 0), was not associated with a significant difference in the risk of CD/MI [HR 1.09; CI .70-1.69; P = .693], but was associated with a significant increase in the risk of CR (HR 5.62; CI 3.08-10.25; P < .001) and LCR (HR 2.98; CI 1.36-6.53; P = .006). CONCLUSION: Near-normal MPI and borderline ischemia on SPECT-MPI provide no significant prognostic information in predicting hard cardiac events but are associated with higher rates of obstructive angiographic CAD and coronary revascularizations.

Prognostic value of absent left ventricular ejection fraction reserve with regadenoson SPECT MPI.

BACKGROUND: An absent left ventricular ejection fraction (LVEF) reserve with vasodilator stress with PET cardiac imaging has been shown to provide significant independent and incremental value to the perfusion images for prediction of future cardiovascular adverse events. However, the prognostic value of LVEF reserve has not been well characterized with SPECT myocardial perfusion imaging (MPI). METHODS: We studied 858 consecutive patients with normal and abnormal perfusion pattern with regadenoson SPECT MPI. Change in LVEF was calculated as post-stress LVEF-rest LVEF. Absent LVEF reserve was defined as a drop in LVEF by 5% or more on the post-stress images. The primary outcome was a composite of cardiac death, non-fatal myocardial infarction and late coronary revascularization. RESULTS: An absent LVEF reserve was more common in patients with abnormal vs normal MPI (31% vs 19%, P = .001). During a median follow-up of 32 months, the primary outcome was experienced by 31% of the study population. An absent LVEF reserve was not associated with an increased risk of the primary outcome in patients with normal (hazard ratio 1.1, 95% CI .4-2.7, P = .8) or abnormal (.75, .56-1.00, P = .05) MPI. There was no significant correlation between extent of ischemia and post-stress change in LVEF (Pearson r = - .072, P = .07). CONCLUSIONS: In patients undergoing regadenoson SPECT MPI, absent LVEF reserve is not associated with worse cardiac outcomes. Thus, routine reporting of both post-stress and rest LVEF measurements in this setting may not be necessary.

Left ventricular ejection fraction, myocardial blood flow and hemodynamic variables in adenosine and regadenoson vasodilator 82-Rubidium PET.

AIMS: In most Rubidium-(Rb)-positron emission tomography (PET) studies, dipyridamole was used as vasodilator. The aim was to evaluate vasodilator PET left ventricular ejection fraction (LVEF), myocardial blood flow (MBF), hemodynamics, and the influence of adenosine and regadenoson on these variables. METHODS AND RESULTS: Consecutive patients (N = 2299) with prior coronary artery disease (CAD) or no prior CAD undergoing adenosine/regadenoson 82Rb-PET were studied and compared according to CAD status and normal/abnormal PET (summed stress score 0-3 vs. ≥4). Rest and stress LVEF differed significantly depending on CAD status and scan results. In patients with no prior CAD, rest/stress LVEF were 68% and 72%, in patients with prior CAD 60% and 63%. LVEF during stress increased 5 ± 6% in normal compared to 1 ± 8% in abnormal PET (P<0.001). Global rest myocardial blood flow(rMBF), stress MBF(sMBF) and myocardial flow reserve (sMBF/rMBF) were significantly higher in no prior CAD patients compared to prior CAD patients(1.3 ± 0.5, 3.3 ± 0.9, 2.6 ± 0.8 and 1.2 ± 0.4, 2.6 ± 0.8, 2.4 ± 0.8 ml/g/min, respectively, P<0.001) and in normal versus abnormal scans, irrespective of CAD status(no prior CAD: 1.4 ± 0.5, 3.5 ± 0.8, 2.8 ± 0.8 and 1.2 ± 0.8, 2.5 ± 0.8, 2.2 ± 0.7; prior CAD: 1.3 ± 0.4, 3.1 ± 0.8, 2.7 ± 0.8 and 1.1 ± 0.4, 2.3 ± 0.7, 2.2 ± 0.7 ml/g/min, respectively, P<0.001). LVEF and hemodynamic values were similar for adenosine and regadenoson stress. Stress LVEF ≥70% excluded relevant ischemia (≥10%) with a negative predictive value (NPV) of 94% (CI 92-95%). CONCLUSIONS: Rest/stress LVEF, LVEF reserve and MBF values are lower in abnormal compared to normal scans. Adenosine and regadenoson seem to have similar effect on stress LVEF, MBF and hemodynamics. A stress LVEF ≥70% has a high NPV to exclude relevant ischemia.

Development and validation of a hydrophilic interaction liquid chromatography-tandem mass spectrometry method for the quantification of regadenoson in human plasma and its pharmacokinetic application.

Regadenoson, the first selective adenosine A2A receptor agonist, is used to perform exercise stress test during radionuclide myocardial perfusion imaging. To detect the concentration of regadenoson in human plasma, a simple, fast, and sensitive tandem mass spectrometry method was established herein. Acetonitrile was used as a protein precipitation agent. Chromatographic separation was completed in 6.5 min using a BEH HILIC column (50 × 2.1 mm, 1.7 µm). The mobile phase consisted of 10 mmol/L ammonium acetate/acetonitrile (gradient elution). To quantify regadenoson and regadenoson-d3, an API 4000 mass spectrometry in multiple reaction monitoring mode with transitions of 391.3→259.2 and 394.3→262.2, respectively, was utilized. The calibration curve was linear in the range of 0.100-50.0 µg/L, and the intrabatch and interbatch precisions were <9.7% and <13.0%, respectively, and the accuracy was 2.0-6.9%. There was no apparent matrix effect for regadenoson or regadenoson-d3. The developed method was used to study the pharmacokinetic characteristics of regadenoson in healthy Chinese subjects.

The prognostic value of regadenoson SPECT myocardial perfusion imaging: The largest cohort to date.

BACKGROUND: Data on the prognostic value of regadenoson SPECT myocardial perfusion imaging (MPI) is limited and based on small cohorts. METHODS AND RESULTS: We conducted a single-center, retrospective cohort study of 10,275 consecutive patients who underwent regadenoson SPECT-MPI. Among the study subjects, 28.7% had abnormal MPI and 25.5% had myocardial ischemia. Patients were followed for a mean of 2.4 ± 2.2 years for major adverse cardiac events (MACE), defined as cardiac death or myocardial infarction. There was a significant stepwise increase in MACE with an increasing burden of perfusion abnormality (P < .001) and myocardial ischemia (P < .001). Abnormal MPI (adjusted HR 1.52; 95% CI 1.21 to 1.91) and myocardial ischemia (adjusted HR 1.53; 95% CI 1.25 to 1.89) were associated with MACE, independent of and incremental to clinical covariates and left ventricular ejection fraction (LVEF). Moreover, post-stress LVEF, LVEF reserve, and left ventricular end-diastolic volume added significant prognostic information. Transient ischemic dilation ≥ 1.31 did not provide incremental prognostic value (adjusted HR 1.02; P = .906). CONCLUSION: In the largest cohort to date, we demonstrated that the presence and severity of perfusion abnormality and myocardial ischemia on regadenoson stress SPECT-MPI are associated with an independent increase in MACE.

Initial experience with regadenoson stress positron emission tomography in patients with left bundle branch block: Low prevalence of septal defects and high accuracy for obstructive coronary artery disease.

BACKGROUND: Assessing for coronary artery disease (CAD) in patients with left bundle branch block (LBBB) is difficult with noninvasive cardiac imaging. Few studies report the prevalence of LBBB associated septal-apical perfusion defects using regadenoson stress on Positron Electron Tomography (PET) imaging. METHODS AND RESULTS: We identified 101 consecutive patients with baseline LBBB, and without known CAD, who underwent rest-stress regadenoson PET. Investigators have the ability to prospectively identify studies, whose quality is limited by LBBB artifact. With the infusion of regadenoson, resting to peak stress heart rate rose from a median of 78 to 93 BPM. Despite this, LBBB perfusion artifacts were not identified in any studies. 10 individuals had both regadenoson SPECT and PET within 1 year. 3 of the 10 SPECT studies had LBBB artifacts, all of which were not seen on subsequent PET. 21 patients with PET had subsequent coronary angiography. Of these, 9 PETs were without significant inducible ischemia, and angiogram was without flow-limiting disease. 3 PETs identified inducible ischemia, but did not have flow-limiting disease on angiogram. 9 PETs identified inducible ischemia and had flow-limiting disease on angiogram. CONCLUSIONS: In patients with LBBB undergoing regadenoson PET stress imaging, artifactual septal perfusion defects are rare.

Prognostic value of regadenoson stress myocardial perfusion imaging in patients with left bundle branch block or ventricular paced rhythm.

BACKGROUND: Vasodilator stress myocardial perfusion imaging (MPI) is the provocative test of choice in patients with left bundle branch block (LBBB) or ventricular paced (V-paced) rhythm. The prognostic value of regadenoson SPECT myocardial perfusion imaging (MPI) in these patients has not been studied. METHODS AND RESULTS: We conducted a retrospective cohort study of 562 patients [mean age, 69 ± 11 years; men, 53.3%] with LBBB (50.7%) or V-paced rhythm (49.3%) who underwent regadenoson stress SPECT-MPI. There were 321 (57.1%) subjects with abnormal MPI and 192 (34.2%) with myocardial ischemia. During a mean follow-up of 2.5 ± 1.9 years, 39 (6.9%) patients had a major adverse cardiac event (MACE), defined as cardiac death or myocardial infarction. The annualized MACE rate in patients with normal MPI was 0.9% (LBBB, 0.8%; V-paced, 1.0%). There was a significant stepwise increase in MACE rates with increasing burdens of perfusion abnormality (P < 0.001) and myocardial ischemia (P = 0.001). Increased risk with abnormal MPI [adjusted hazard ratio, 4.26; P = 0.001] and myocardial ischemia [adjusted hazard ratio, 2.70; P = 0.003] was independent of and incremental to important clinical covariates. Abnormal MPI and myocardial ischemia predicted MACE similarly in both LBBB and V-paced subgroups (interaction P values > 0.05). CONCLUSION: In patients with LBBB and V-paced rhythm, regadenoson stress SPECT-MPI provides independent and incremental prognostic value in predicting adverse cardiac events.

Practical instructions for using drugs in CT and MR cardiac imaging.

The progressive increase in numbers of noninvasive cardiac imaging examinations broadens the spectrum of knowledge radiologists are expected to acquire in the management of drugs during CT coronary angiography (CTCA) and cardiac MR (CMR) to improve image quality for optimal visualization and assessment of the coronary arteries and adequate MR functional analysis. Aim of this review is to provide an overview on different class of drugs (nitrate, beta-blockers, ivabradine, anxiolytic, adenosine, dobutamine, atropine, dipyridamole and regadenoson) that can be used in CTCA and CMR, illustrating their main indications, contraindications, efficacy, mechanism of action, metabolism, safety, side effects or complications, and providing advices in their use.

Stimulation of the hepatic arterial buffer response using exogenous adenosine: hepatic rest/stress perfusion imaging.

OBJECTIVES: The hepatic arterial buffer response is a mechanism mediated by adenosine whereby hepatic arterial perfusion (HAP) increases when portal flow decreases, and is implicated in liver disease. The first study aim was to measure HAP in patients undergoing myocardial perfusion imaging (MPI), thus developing hepatic arterial rest/stress perfusion imaging (HAPI). The second aim was to compare adenosine-induced changes in splenic perfusion (SP) and HAP with corresponding changes in myocardial blood flow (MBF). METHODS: Patients had MPI with 82Rb PET/CT using adenosine (n = 45) or regadenoson (n = 33) for stressing. SP and HAP were measured using a first-pass technique that gives HAP rather than total hepatic perfusion. Renal perfusion (RP) was also measured. RESULTS: Mean MBF and HAP increased after both adenosine ([stress-rest]/rest 1.1 and 0.8) and regadenoson (1.4 and 0.6), but the respective changes did not correlate. After adenosine, SP (- 0.48) and RP (- 0.26) both decreased. The change in SP correlated positively with the change in MBF (r = 0.36; p = 0.015) but did not correlate with change in HAP. After regadenoson, SP (0.2) and RP (0.2) both increased. The changes in SP correlated with the changes in MBF (r = 0.39; p = 0.025) and HAP (r = 0.39; p = 0.02). Changes in RP correlated with changes in HAP (r = 0.51; p = 0.0008) but not MBF. Resting SP (r = 0.32; p = 0.004), but not resting HAP, correlated with hepatic fat burden. Adenosine-induced change in HAP also correlated with hepatic fat (r = 0.29; p = 0.05). CONCLUSION: HAPI could be a useful new hepatic function test. Neither splenic 'switch-off' nor hepatic arterial 'switch-on' identifies adequacy of stress in MPI. KEY POINTS: • This article describes a new method for assessing arterial perfusion of the liver and its capacity to respond to an infusion of adenosine, a substance that normally 'drives' hepatic arterial flow. • Hepatic arterial flow increased in response to adenosine, sometimes dramatically. Adenosine is already used clinically to stimulate myocardial blood flow in patients with suspected coronary disease, but the increase in flow did not correlate with the corresponding increase in hepatic arterial flow. • Analogous to the use of adenosine in the myocardium, the increase in hepatic arterial flow in response to adenosine has the potential to be a new clinically useful method for the evaluation of hepatic arterial haemodynamics in liver disease.

Risk stratification with vasodilator stress SPECT myocardial perfusion imaging in patients with elevated cardiac biomarkers.

BACKGROUND: Although the diagnostic accuracy and prognostic utility of vasodilator stress MPI have been well established in the non-acute setting, the efficacy of all of the vasodilator stressors in risk stratifying post-MI patients as well as the evaluation of cardiac troponin elevation of unclear etiology is not established. Accordingly, the aim of the present study was to investigate the prognostic efficacy of vasodilator stress MPI in the setting of elevated cardiac troponin to accurately risk stratify these higher-risk patients. METHODS: All patients from two tertiary centers, from 1/1/2010 through 12/31/2012, with elevated cardiac biomarkers within < 7 days and undergoing stress SPECT MPI testing were studied. Results of stress MPI were scored using a 17-segment model based on semiquantitative scoring as normal or abnormal (mild, moderate, or severe) using a total perfusion defect (TPD) of 0%, 1-10%, 10-20%, and > 20%. Mortality data through the year 2014 were obtained from the National Death Index, and survival analyses were performed. The primary endpoint was all-cause mortality with the secondary endpoint being cardiac mortality. RESULTS: A total of 503 patients were followed for an average of 33.6 ± 16.2 months, with a mean age of 69.3 years; 53.7% male; and a majority (88.7%) of them undergoing vasodilator stress. A significant increase in all-cause mortality was seen based on the severity of TPD results for all vasodilators (P < .0001) and regadenoson (P < .0001). Similar prognostic ability was seen for all-cause mortality. This association was maintained even after adjustment for cardiac risk factors, previous coronary disease, and troponin quartiles. MPI results (stress TPD and LVEF) added to traditional cardiac risk factors, and troponin values resulted in a significant incremental increase in the ability to predict all-cause and cardiac mortality, and stress TPD remained independently predictive for both all-cause and cardiac mortality in a multivariate model. CONCLUSION: Vasodilator stress (including regadenoson) MPI effectively risk stratifies patients with recently elevated cardiac biomarkers, with the increasing risk of mortality with the increasing severity of perfusion defects. It provides incremental prognostic value, in addition to clinical factors and degree of troponin elevation.

Regadenoson myocardial perfusion scintigraphy for the evaluation of coronary artery disease in patients with lung disease: A series of five cases.

Coronary artery disease (CAD) is a leading cause of death and morbidity globally. Myocardial perfusion scintigraphy (MPS) is commonly used for the diagnosis of CAD, necessitating hyperaemia achieved either by physical exertion or by pharmacological stress, most commonly through use of a coronary arteriolar dilator. This is challenging in patients with respiratory conditions because exercise may be submaximal and adenosine is contraindicated because of the risk of bronchoconstriction. Regadenoson is the only selective adenosine A2A receptor agonist approved as a vasodilator in MPS. The risk of bronchospasm with regadenoson has been investigated in large, randomised trials; however, patients with the most severe respiratory conditions were not included. In this case series, we present the use of regadenoson MPS in five patients with moderate-to-severe lung conditions, including patients requiring lung volume reduction surgery and lung transplant. In all cases, regadenoson MPS provided valuable information for risk assessment and treatment optimisation. Although dyspnoea occurred in all patients, regadenoson was well tolerated without serious adverse events or bronchospasm; in no case was intervention required to treat dyspnoea.